Targeted nanocarrier compirisng NANO-colloid suspension of poly(phenyllactic-co-kojic-co-gluconic acid)

Abstract

A targeted nanocarrier for delivering drugs to targeted cells. The targeted nanocarrier may comprise a nano-colloid suspension of poly(phenyllactic-co-kojic-co-gluconic acid) (poly(PLKGA)), the nano colloid suspension of poly(PLKGA) comprising: a dispersed phase comprising a plurality of nanoparticles of poly(PLKGA); and a continuous phase comprising a medium of the nano-colloid suspension of poly(PLKGA).

Description

Ref- 1403-02-8765TARGETED NANOCARRIER COMPIRISNG NANO-COLLOID SUSPENSION OF POLY(PHENYLLACTIC-CO-KOJIC-CO-GLUCONIC ACID)TECHNICAL FIELD

[0001] The present disclosure is generally related to an exemplary targeted nanocarrier comprising nano-colloid suspension, and more particularly to an exemplary pharmaceutical composition with anti-neoplastic and anti-bacterial properties.BACKGROUND

[0002] Cancer rates have increased in human civilizations due to changes in lifestyle, and chemotherapy continues to be a key component of cancer treatment even with the advent of biological therapies. Side effects are caused by the high distribution volume of chemotherapy and non-selective toxicity. Further, treatment resistance is developed by the free drug metabolism and non-effective concentration in the tumor. Nanocarriers are an established method of targeting tumors and lowering chemotherapy resistance and side effects by enhancing drug stability and delivery. To date, three drug delivery systems have been used to market chemotherapy nanomedicines: liposome, micelle, and colloid.

[0003] However, most chemotherapy nanomedicines are liposome-based, which were approved for targeted delivery of water-soluble chemotherapeutic s. A lot of chemotherapy drugs are lipophilic, and chemical substitution to make them water-soluble can decrease the medication's potency and raise the therapeutic dose and adverse effects. Therefore, there is a need to design a drug delivery system that specifically carries hydrophobic chemotherapy drugs and delivers drugs to targeted cells with the lowest required dose.SUMMARYRef- 1403-02-8765

[0004] This summary is intended to provide an overview of the subject matter of the present disclosure, and is not intended to identify essential elements or key elements of the subject matter, nor is it intended to be used to determine the scope of the claimed implementations. Its sole purpose is to present some concepts of one or more exemplary aspects in a simplified form as a prelude to the more detailed description that is presented later. The proper scope of the present disclosure may be ascertained from the claims set forth below in view of the detailed description below and the drawings.

[0005] One or more exemplary embodiments describe an exemplary targeted nanocarrier for delivering drugs to targeted cells. In an exemplary embodiment, an exemplary targeted nanocarrier may comprise an exemplary nano-colloid suspension of poly(phenyllactic-co- kojic-co-gluconic acid) (poly(PLKGA)). In an exemplary embodiment, an exemplary nanocolloid suspension of poly(PLKGA) may comprise: an exemplary dispersed phase comprising a plurality of exemplary nanoparticles of poly(PLKGA); and an exemplary continuous phase comprising an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA). In an exemplary embodiment, an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA) may comprise an exemplary biocompatible hydrophilic fluid. In an exemplary embodiment, an exemplary targeted nanocarrier may comprise an exemplary nano-colloid suspension of poly(PLKGA) with a concentration between 0.9 mg / ml and 1.1 mg / ml. In an exemplary embodiment, exemplary nanoparticles of poly(PLKGA) may be coated with polyvinyl alcohol with a molecular weight between 30-70 kDa. In an exemplary embodiment, an exemplary biocompatible hydrophilic fluid may comprise water and sorbitol. In an exemplary embodiment, an exemplary targeted nanocarrier may have an anti-bacterial and anti-neoplastic activity.

[0006] One or more exemplary embodiments describe an exemplary anti-neoplastic and anti-bacterial composition. In an exemplary embodiment, an exemplary anti-neoplastic andRef- 1403-02-8765 anti-bacterial composition may comprise an exemplary nano-colloid suspension of poly(PLKGA) bound 7-Ethyl-10-hydroxycamptothecin (SN-38). In an exemplary embodiment, an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise: an exemplary dispersed phase comprising a plurality of exemplary poly(PLKGA) bound SN-38 exemplary nanoparticles; and an exemplary continuous phase comprising an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA) bound SN- 38. In an exemplary embodiment, an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise an exemplary biocompatible hydrophilic fluid. In an exemplary embodiment, an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise poly(PLKGA) and SN-38 with a weight ratio of 100: 1 (poly(PLKGA):SN-38). In an exemplary embodiment, each exemplary nanoparticle of poly(PLKGA) bound SN-38 may be coated with polyvinyl alcohol with a molecular weight between 30-70 kDa. In an exemplary embodiment, an exemplary biocompatible hydrophilic fluid may comprise water and sorbitol. In an exemplary embodiment, an exemplary biocompatible hydrophilic fluid may fill the space between the poly(PLKGA) bound SN-38 exemplary nanoparticles.

[0007] In an exemplary embodiment, an exemplary method of producing polyphenyllactide with a purity ranging between 90 wt% and 95 wt% may comprise: forming an exemplary white solid comprising phenyllactide through an esterification reaction by adding an exemplary catalyst comprising anhydrous zinc chloride with a concentration of 1% w / w (with respect to the weight of phenyllactic acid) to phenyllactic acid while stirring in an exemplary first storage connected to nitrogen gas flow, at a temperature level between 125 °C and 135 °C, and for a time duration between 25 minutes and 35 minutes while the first storage is placed in an exemplary paraffin bath; forming an exemplary hard yellow gel comprising polyphenyllactide through ring opening polymerization reaction by adding anRef- 1403-02-8765 exemplary catalyst comprising tin(II) octoate with a concentration of 1% w / w (with respect to the weight of phenyllactide) to an exemplary white solid comprising phenyllactide in an exemplary first storage connected to nitrogen gas flow while stirring without reflux at a temperature level between 175 °C and 185 °C, and for a time duration between 55 minutes and 65 minutes; and forming an exemplary hard fragile polymeric glass comprising polyphenyllactide by cooling an exemplary hard yellow gel comprising polyphenyllactide to a temperature level between 20 °C and 25 °C, and for a time duration between 10 minutes and 15 minutes.

[0008] In an exemplary embodiment, an exemplary method of producing oligo(kojic-co- gluconic acid) with a purity ranging between 90 wt% and 95 wt% may comprise: forming an exemplary melted mixture comprising oligo(kojic-co-gluconic acid) by mixing / stirring an exemplary freeze dried powder of kojic acid with an exemplary freeze dried powder of gluconic acid with a molar ratio of 1 : 1 (kojic acid: gluconic acid) on a stirrer at a temperature level between 110 °C and 130 °C, for a time duration of between 25 minutes and 35 minutes, under vacuum using a vacuum pump, and in a presence of exemplary catalysts comprising tin(II) octoate and zinc chloride with a final concentration of 1% w / w individually; forming an exemplary yellow solid comprising oligo(kojic-co-gluconic acid) by cooling an exemplary melted mixture to a temperature level of 25 °C; and forming an exemplary pure precipitate of oligo(kojic-co-gluconic acid) by washing excess amounts of kojic acid and gluconic acid from an exemplary yellow solid.

[0009] In an exemplary embodiment, an exemplary method of producing poly(PLKGA) with a purity ranging between 90 wt% and 95 wt% may comprise: forming an exemplary first solution comprising an exemplary diphenyl ether solution of polyphenyllactide with a concentration between 240 mg / ml and 260 mg / ml by dissolving polyphenyllactide in diphenyl ether on a stirrer at a temperature level between 150 °C and 170 °C, under reflux;Ref- 1403-02-8765 cooling an exemplary first solution to a predetermined temperature level of 110 °C; forming an exemplary second solution comprising an exemplary diphenyl ether solution of poly(PLKGA) by adding an exemplary powder of pure oligo(kojic-co-gluconic acid) with a concentration of 10% w / w (with respect to the weight of an exemplary powder of polyphenyllactide) to an exemplary cooled first solution while stirring on a stirrer at a temperature level between 105 °C and 115 °C and for a time duration of about 12 minutes and 18 minutes; cooling an exemplary second solution to a temperature level of 25 °C; forming an exemplary precipitate of poly(PLKGA) by adding an exemplary anti- solvent comprising ethanol solution to an exemplary cooled second solution with a predetermined volume ratio of 1: 10 (an exemplary cooled second solution: an exemplary anti- solvent); washing an exemplary precipitate of poly(PLKGA) by an exemplary solvent comprising ethanol solution with a concentration of at least 95% (v / v); and drying an exemplary washed precipitate at a temperature level of 40 °C by using an oven.

[0010] This Summary may introduce a number of concepts in a simplified format; the concepts are further disclosed within the “Detailed Description” section. This Summary is not intended to configure essential / key features of the claimed subject matter, nor is intended to limit the scope of the claimed subject matter.BRIEF DESCRIPTION OF THE DRAWINGS

[0011] The novel features which are believed to be characteristic of the present disclosure, as to its structure, organization, use and method of operation, together with further objectives and advantages thereof, will be better understood from the following drawings in which an exemplary embodiment will now be illustrated by way of example. It is expressly understood, however, that the drawings are for the purpose of illustration and description only and are not intended as a definition of the limits of one or more exemplary embodiments.Ref- 1403-02-8765One or more exemplary embodiments will now be described by way of example in association with the accompanying drawings in which:

[0012] FIG. 1 illustrates an exemplary flowchart of exemplary method for preparing an exemplary nanocarrier comprising an exemplary nano-colloid suspension of poly(phenyllactic-co-kojic-co-gluconic acid) (poly(PLKGA)), consistent with one or more exemplary embodiments of the present disclosure;

[0013] FIG. 2A illustrates an exemplary method of step for producing polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0014] FIG. 2B illustrates a nuclear magnetic resonance spectrum (XH NMR) of phenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0015] FIG. 2C illustrates the Carbon-13 nuclear magnetic resonance (13C NMR) spectrum of phenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0016] FIG. 2D illustrates the Liquid chromatography-mass (LC-MS) spectrum of phenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0017] FIG. 2E illustrates1H NMR of polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0018] FIG. 2F illustrates the Gel permeation chromatography (GPC) spectrum of polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0019] FIG. 3A illustrates exemplary reaction scheme for producing oligo(kojic-co- gluconic acid), consistent with one or more exemplary embodiments of the present disclosure;Ref- 1403-02-8765

[0020] FIG. 3B illustrates an exemplary method of step for producing oligo(kojic-co- gluconic acid), consistent with one or more exemplary embodiments of the present disclosure;

[0021] FIG. 3C illustrates an1H NMR spectrum of kojic acid, consistent with one or more exemplary embodiments of the present disclosure;

[0022] FIG. 3D illustrates an1H NMR spectrum of gluconic acid, consistent with one or more exemplary embodiments of the present disclosure;

[0023] FIG. 3E illustrates an1H NMR spectrum of oligo(kojic-co-gluconic acid) and kojic acid, consistent with one or more exemplary embodiments of the present disclosure;

[0024] FIG. 3F illustrates an ’ H NMR spectrum of oligo(kojic-co-gluconic acid), consistent with one or more exemplary embodiments of the present disclosure;

[0025] FIG. 4A illustrates exemplary reaction scheme for linking oligo(kojic-co- gluconic acid) to polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0026] FIG. 4B illustrates an exemplary method of step for linking oligo(kojic-co- gluconic acid) to polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure;

[0027] FIG. 4C illustrates the comparison of ’ H NMR spectra of polyphenyllactide (right) and poly(PLKGA) (left), consistent with one or more exemplary embodiments of the present disclosure;

[0028] FIG. 4D illustrates the1H NMR spectrum of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure;

[0029] FIG. 5 illustrates an exemplary method of step for forming an exemplary nanocolloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure;Ref- 1403-02-8765

[0030] FIG. 6 illustrates an exemplary flowchart of exemplary method for producing an exemplary anti-neoplastic and anti-bacterial composition comprising an exemplary nanocolloid suspension of poly(PLKGA) bound SN-38, consistent with one or more exemplary embodiments of the present disclosure;

[0031] FIG. 7 illustrates the standard curve of fluorescence intensity of the free form of SN-38 (mean ± SD, N = 3), consistent with one or more exemplary embodiments of the present disclosure;

[0032] FIG. 8A illustrates the loading content of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 by increasing the initial amount of SN-38 (mean ± SD, N = 3), consistent with one or more exemplary embodiments of the present disclosure;

[0033] FIG. 8B illustrates the encapsulation efficiency of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 nanoparticles by increasing the initial amount of SN-38 (mean ± SD, N = 3), consistent with one or more exemplary embodiments of the present disclosure;

[0034] FIG. 8C illustrates Atomic Force Microscopy (AFM) images of poly(PLKGA) bound SN-38 nanoparticles, consistent with one or more exemplary embodiments of the present disclosure;

[0035] FIG. 8D illustrates scanning electron microscope (SEM) images of poly(PLKGA) bound SN-38 nanoparticles, consistent with one or more exemplary embodiments of the present disclosure;

[0036] FIG. 8E illustrates the SEM image of an exemplary nano-colloid suspension of poly(PLKGA) (1 mg / ml), consistent with one or more exemplary embodiments of the present disclosure;

[0037] FIG. 9 illustrates a graph for presenting cumulative release of SN-38 from an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in phosphate and citrateRef- 1403-02-8765 buffers over time (mean ± SD, N = 3, t = 37 °C), consistent with one or more exemplary embodiments of the present disclosure;

[0038] FIG. 10A illustrates the graph for presenting C26 cell line viability test after 3- hour treatment of free SN-38, poly(PLKGA) and poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0039] FIG. 10B illustrates half-maximal inhibitory concentration value (IC50) calculation of free SN-38 in C26 cell line after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0040] FIG. 10C illustrates IC50 calculation of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in C26 cell line after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0041] FIG. 10D illustrates statistical comparison of the viability of C26 cell line after 3-hour treatment of 1.25 pg / ml free SN-38 and 1.25 pg / ml poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0042] FIG. 10E illustrates graph of HCT116 cell line viability test after 3 hour treatment of free SN-38, poly(PLKGA) and poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0043] FIG. 10F illustrates IC50 calculation of free SN-38 in HCT116 cell line after 3- hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0044] FIG. 10G illustrates IC50 calculation of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in HCT116 cell line after 3-hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure;Ref- 1403-02-8765

[0045] FIG. 10H illustrates statistical comparison of the viability of HCT116 cell line after 3 -hour treatment of 2.5 pg / ml free SN-38 and 2.5 pg / ml poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0046] FIG. 101 illustrates the graph of CHO cell line viability test after 3 -hour treatment of free SN-38, poly(PLKGA) and poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0047] FIG. 10J illustrates statistical comparison of the viability of CHO cell line after 3-hour treatment of 5 pg / ml free SN-38 and 5 pg / ml poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure;

[0048] FIG. 10K illustrates IC50 calculation of an exemplary nano-colloid suspension of poly(PLKGA) cell lines after 3 -hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure.

[0049] FIG. 11A illustrates flow cytometry histogram of C26 cell line after 90 minutes of treatment with 10 pg / ml free SN-38 and 10 pg / ml poly(PLKGA) bound SN-38, consistent with one or more exemplary embodiments of the present disclosure;

[0050] FIG. 11B illustrates flow cytometry histogram of HCT116 cell line after 90- minutes of treatment with 10 pg / ml free SN-38 and 10 pg / ml poly(PLKGA) bound SN-38, consistent with one or more exemplary embodiments of the present disclosure;

[0051] FIG. 12 illustrates the image of optical microscope, fluorescence microscope and integrated images of C26 cell line after 90-minute treatment of 10 pg / ml free SN-38 and 10 pg / ml of poly(PLKGA) bound SN-38;

[0052] FIG. 13 illustrates the image of optical microscope, fluorescence microscope and integrated images of HCT116 cell line after 90-minute treatment of 10 pg / ml free SN-38 and 10 pg / ml poly(PLKGA) bound SN-38;Ref- 1403-02-8765

[0053] FIG. 14 illustrates the optical microscope image of HCT116 cell line after 24- hour treatment of 10 pg / ml free SN-38 and fluorescence emission of the same image;

[0054] FIG. 15 illustrates the optical microscope image of HCT116 cell line after 24- hour treatment of 10 pg / ml poly(PLKGA) bound SN-38 and fluorescence emission of the same image;

[0055] FIG. 16A illustrates average tumor volume of mice during 22-days (mean ± SD, N = 6, injection days 1, 4 and 7), consistent with one or more exemplary embodiments of the present disclosure;

[0056] FIG. 16B illustrates statistical analysis of the difference in final average tumor volume of mice (mean ± SD, N = 6), consistent with one or more exemplary embodiments of the present disclosure;

[0057] FIG. 16C illustrates average weight of mice during the test of anti-tumor activity (mean ± SD, N = 6), consistent with one or more exemplary embodiments of the present disclosure;

[0058] FIG. 16D illustrates statistical analysis of the difference in final average weight of mice during the test of anti-tumor activity (mean ± SD, N = 6), consistent with one or more exemplary embodiments of the present disclosure;

[0059] FIG. 17A illustrates optical microscope images of the mouse liver tissue at the end of anti-tumor activity test, after three injections of free SN-38 and an exemplary nanocolloid suspension of poly(PLKGA) bound SN-38 (total 240 pg (12 mg / kg)) (the dose of poly(PLKGA) was equal to the polymer in poly(PLKGA) bound SN-38), consistent with one or more exemplary embodiments of the present disclosure;

[0060] FIG. 17B illustrates optical microscope images (10X magnification) of the mouse organ tissue anti-tumor activity test, after three injections of free SN-38 and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 (total 240 pg (12 mg / kg))Ref- 1403-02-8765(the dose of poly(PLKGA) was equal to the polymer in poly(PLKGA) bound SN-38), consistent with one or more exemplary embodiments of the present disclosure;

[0061] FIG. 17C illustrates optical microscope images (10X magnification) of the mouse tumor tissue at the end of anti-tumor activity test, after three injections of free SN-38 and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 (total 240 pg (12 mg / kg)) (the dose of poly(PLKGA) was equal to the polymer in poly(PLKGA) bound SN-38), consistent with one or more exemplary embodiments of the present disclosure; and

[0062] FIG. 18 illustrates fluorescence images 1800 of the mouse organs, 6 hours and 24 hours after intravenous injection of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in comparison to intravenous injection of sodium chloride 0.9%, consistent with one or more exemplary embodiments of the present disclosure.DETAILED DESCRIPTION

[0063] In the following detailed description, numerous specific details are set forth by way of examples to provide a thorough understanding of the relevant teachings related to exemplary embodiments. However, it should be apparent that the present teachings may be practiced without such details. In other instances, well known methods, procedures, components, and / or circuitry have been described at a relatively high-level, without detail, in order to avoid unnecessarily obscuring aspects of the present teachings.

[0064] The following detailed description is presented to enable a person skilled in the art to make and use the methods and devices disclosed in one or more exemplary embodiments. For purposes of explanation, specific nomenclature is set forth to provide a thorough understanding of one or more exemplary embodiments. However, it will be apparent to one skilled in the art that these specific details are not required to practice the disclosed exemplary embodiments. Descriptions of specific exemplary embodiments are provided only as representative examples. Various modifications to exemplaryRef- 1403-02-8765 implementations will be plain to one skilled in the art, and the general principles defined herein may be applied to other implementations and applications without departing from the scope of one or more exemplary embodiments. The present disclosure is not intended to be limited to the implementations shown, but is to be accorded the widest possible scope consistent with the principles and features disclosed herein.

[0065] An exemplary embodiment is directed to an exemplary targeted nanocarrier for delivering drugs to exemplary target cells. In an exemplary embodiment, an exemplary targeted nanocarrier may comprise an exemplary nano-colloid suspension of poly(phenyllactic-co-kojic-co-gluconic acid) (poly(PLKGA)). In an exemplary embodiment, an exemplary targeted nanocarrier may comprise an exemplary nano-colloid suspension of poly(PLKGA) with a concentration between 0.9 mg / ml and 1.1 mg / ml (with respect to the final concentration of an exemplary nano-colloid suspension of poly(PLKGA)). “Colloid” may refer to a uniform, non-crystalline mixture made up of big molecules or minuscule particles of one material dispersed through another. In an exemplary embodiment, an exemplary nano-colloid suspension of poly(PLKGA) may have an anti-neoplastic and antibacterial properties. In an exemplary embodiment, an exemplary nano-colloid suspension of poly(PLKGA) may comprise an exemplary dispersed phase and an exemplary continuous phase. In an exemplary embodiment, an exemplary dispersed phase may comprise a plurality of exemplary nanoparticles of poly(PLKGA). In an exemplary embodiment, each exemplary nanoparticle of poly(PLKGA) may be coated with polyvinyl alcohol (with a molecular weight between 30-70 kDa). In an exemplary embodiment, an exemplary continuous phase may comprise an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA). In an exemplary embodiment, an exemplary medium of an exemplary nanocolloid suspension of poly(PLKGA) may comprise an exemplary biocompatible hydrophilicRef- 1403-02-8765 fluid. In an exemplary embodiment, an exemplary biocompatible hydrophilic fluid may comprise water and sorbitol.

[0066] Lactic acid monomers are the building blocks of biodegradable polylactic acid (PLA), a safe and FDA-approved drug delivery carrier. Lactic acid hydroxyl and carboxyl functional groups may be esterified to create PLA polymers with varying molecular masses. Ultimately, the OH and COOH at either end of the chain may react with medications, polymers, and targeting molecules like aptamers and antibodies. Because of the lipophilic qualities of the phenyl group in the derivative, polyphenyllactide is more hydrophobic than polylactic acid and better suited for the binding of lipophilic medicines. Gluconic acid and kojic acid fabricate polyphenyllactide to increase targeting and nanocarrier uptake by the cancer cell. Gluconic acid (pKa = 3.6) has a high affinity for glucose transporters (GLUT) which are extensively expressed on the surface of cancer cells and enhances the process of nanocarrier endocytosis. Kojic acid may be employed as an intermediary to boost the reactivity of non-polar polyphenyllactide with gluconic acid which is highly polar, due to one carboxyl and five hydroxyl groups. Kojic acid (pKa = 7.6) may bind gluconic acid to polyphenyllactide by esterification, since it contains two hydroxyl groups, one of which is acidic due to its closeness to carbonyl. Consequently, the capability of dissolving hydrophobic chemotherapeutic s and inherent anti-neoplastic activity of poly(PLKGA) nanoparticles may enhance the effects of chemotherapy while mitigating drug resistance and adverse effects.

[0067] Most chemotherapy nanomedicines are liposome -based which were approved for targeted delivery of water-soluble chemotherapeutic s. A lot of chemotherapy drugs are lipophilic, and chemical substitution to make them water soluble, may decrease the medication potency and raise therapeutic dose and adverse effects. So, development of micellar and colloidal platforms for delivery of poorly water-soluble chemotherapeutic s isRef- 1403-02-8765 essential. On the other hand, using multi-targeted systems is important to reduce drug resistance and enhance treatment. Hence, synthesis and preparation of a colloidal system with intrinsic anti-bacterial and anti-neoplastic activity and targeted delivery of SN-38 (water insoluble active metabolite of irinotecan) was done to synergize chemotherapy and reduce SN-38 resistance and side effects.

[0068] Polyphenyllactic acid may be linked to gluconic acid to enhance the polymer uptake into the cancer cell since, gluconic acid facilitates the polymer endocytosis by binding to glucose transporters (GLUT), that are highly expressed on the surface of cancer cells. While polyphenyllactic acid is non-polar, gluconic acid is highly polar, so kojic acid may be used as an intermediate for the reaction. Kojic acid also has inhibitory effects on tyrosinase and cancer cell proliferation. Therefore, poly(PLKGA) with intrinsic anti-neoplastic activity may be introduced as a colloidal drug delivery system for hydrophobic chemotherapeutic s in the present disclosure.

[0069] Referring to the figures, FIG. 1 illustrates an exemplary flowchart of exemplary method 100 for preparing an exemplary nanocarrier comprising an exemplary nano-colloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, exemplary method 100 may comprise: producing polyphenyllactide (step 102); producing oligo(kojic-co-gluconic acid) (step 104); linking oligo(kojic-co-gluconic acid) to polyphenyllactide (step 106); forming an exemplary colloid suspension of poly(PLKGA) (step 108); and forming an exemplary nano colloid suspension of poly(PLKGA) (step 110).

[0070] In further detail with respect to step 102, step 102 may include producing polyphenyllactide. In an exemplary embodiment, details of step 102 for producing polyphenyllactide are described in context of elements presented in FIG. 2A. FIG. 2A illustrates an exemplary method of step 102 for producing polyphenyllactide, consistent withRef- 1403-02-8765 one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, an exemplary method 102 may comprise: forming an exemplary white solid comprising phenyllactide through an esterification reaction (step 200); forming an exemplary hard yellow gel comprising polyphenyllactide through ring opening polymerization reaction (step 202); and forming an exemplary hard fragile polymeric glass comprising polyphenyllactide (step 204).

[0071] In further detail with respect to step 200, step 200 may include forming an exemplary white solid comprising phenyllactide through an esterification reaction. In an exemplary embodiment, forming an exemplary white solid comprising phenyllactide through an esterification reaction may comprise adding an exemplary catalyst with a predetermined concentration to an exemplary powder of phenyllactic acid. In an exemplary embodiment, adding an exemplary catalyst with a predetermined concentration to an exemplary powder of phenyllactic acid may comprise adding an exemplary catalyst with a predetermined concentration to an exemplary powder of phenyllactic acid, while stirring in an exemplary first storage connected to a nitrogen gas flow, at a predetermined temperature level, and for a predetermined time duration while an exemplary first storage is placed in a paraffin bath. In an exemplary embodiment, adding an exemplary catalyst with a predetermined concentration to an exemplary powder of phenyllactic acid, while stirring in an exemplary first storage connected to a nitrogen gas flow, at a predetermined temperature level, and for a predetermined time duration while an exemplary first storage is placed in a paraffin bath may comprise adding an exemplary catalyst comprising anhydrous zinc chloride with a concentration of 1% w / w (with respect to the weight of phenyllactic acid) to an exemplary phenyllactic acid while stirring in an exemplary first storage connected to a nitrogen gas flow, at a temperature level between 125 °C and 135 °C, and for a time duration between 25 minutes and 35 minutes while an exemplary first storage is placed in a paraffin bath.Ref- 1403-02-8765

[0072] In further detail with respect to step 202, step 202 may include forming an exemplary hard yellow gel comprising polyphenyllactide through ring opening polymerization reaction. In an exemplary embodiment, forming an exemplary hard yellow gel comprising polyphenyllactide through ring opening polymerization reaction may comprise adding an exemplary catalyst to an exemplary white solid comprising phenyllactide. In an exemplary embodiment, adding an exemplary catalyst to an exemplary white solid comprising phenyllactide may comprise adding an exemplary catalyst with a predetermined concentration to an exemplary white solid comprising phenyllactide in an exemplary first storage connected to nitrogen gas flow while stirring without reflux at a predetermined temperature level, and for a predetermined time duration. In an exemplary embodiment, adding an exemplary catalyst with a predetermined concentration to an exemplary white solid comprising phenyllactide in an exemplary first storage connected to nitrogen gas flow while stirring without reflux at a predetermined temperature level, and for a predetermined time duration may comprise adding an exemplary catalyst comprising tin(II) octoate with a concentration of 1% w / w (with respect to the weight of phenyllactide) to an exemplary white solid comprising phenyllactide in an exemplary first storage connected to nitrogen gas flow while stirring without reflux at a temperature level between 175 °C and 185 °C, and for a time duration between 55 minutes and 65 minutes.In further detail with respect to step 204, step 204 may include forming an exemplary hard fragile polymeric glass comprising polyphenyllactide. In an exemplary embodiment, forming an exemplary hard fragile polymeric glass comprising polyphenyllactide may comprise cooling an exemplary hard yellow gel comprising polyphenyllactide to a predetermined temperature level. In an exemplary embodiment, cooling an exemplary hard yellow gel comprising polyphenyllactide to a predetermined temperature level may comprise cooling an exemplary hard yellow gel comprising polyphenyllactide to a temperature level between 20Ref- 1403-02-8765°C and 25 °C, and for a time duration between 10 minutes and 15 minutes. Referring to the figures, FIG. 2B illustrates a nuclear magnetic resonance spectrum (XH NMR) 206 of phenyllactide, consistent with one or more exemplary embodiments of the present disclosure. In further detail with respect to FIG. 2B, hydrogens (a), appear as a single doublet of doublet peak in the region of 4 ppm, and hydrogens (b), appear as two doublet of doublet peaks in the region of 2.7-3.1 ppm. Phenyl ring hydrogens are also present in the form of multiplet peaks in the aromatic region of 7.3 ppm. Integration of the peaks based on the hydrogen (a) peak (integral = 1), confirmed the double number of hydrogens (b) and fivefold number of phenyl hydrogens, which confirmed the phenyllactide structure. The singlet peak of 6 ppm (integral = 0.8) also confirmed the hydroxyl group in equilibrium with the lactone ring. Referring to the figures, FIG. 2C illustrates the Carbon- 13 nuclear magnetic resonance (13C NMR) spectrum of phenyllactide 208, consistent with one or more exemplary embodiments of the present disclosure. In further detail with respect to FIG. 2C, in the13C NMR spectrum of phenyllactide, the carbonyl carbon, alpha carbon and methylene carbon were seen at 180, 70 and 40 ppm respectively. The phenyl carbons, which are equivalent due to the lack of substitution, were observed as four carbons in the aromatic region of 120-140 ppm. FIG. 2D illustrates the Liquid chromatography-mass (LC-MS) spectrum 210 of phenyllactide, consistent with one or more exemplary embodiments of the present disclosure. In the LC-MS spectrum, the ratio of m / z = 297 (M + 1) and 314 (M + 18) for phenyllactide: m / z = 332 (M + 18) and 337 (M + 23) for diphenyllactic acid: 167 (M + 1), 184 (M + 18) and 189 (M + 23) for phenyllactic acid were detected. FIG. 2E illustratesNMR 212 of polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure. Polyphenyllactide, which was a hard and fragile polymeric glass at ambient temperature, did not dissolve in ethanol and partially dissolved and precipitated in non-polar solvents like chloroform, dichloromethane and ethylacetate, but it dissolved completely inRef- 1403-02-8765DMSO, from which the1H NMR spectrum was prepared. There are three main areas in the spectrum. The region of 2.5-3.5 ppm, which are the peaks related to hydrogens (b) and are observed in the form of multiplet. The 4-6 ppm range, where the three peaks are related to hydrogens (a) and appeared as multiplet, and the aromatic region of 7-8 ppm, where the multiplet peaks represent phenyl hydrogens. Although the hydrogens of polyphenyllactide are similar to phenyllactic acid, but due to the chain structure, the chemical shift of hydrogens at the end of chain is different from the hydrogens in the middle of chain, which is the characteristic of polymer spectrum. Thus, the peak in 4 ppm area corresponds to hydrogen (a), at the end of polymer with free OH group, which is shielded compared to other hydrogens and has less chemical shift. Also, the 5.6 ppm peak corresponds to hydrogen (a), at the other end of polymer with free COOH that tends to be deshielded in comparison to other hydrogens (a). The peak of intermediate hydrogens was also observed in the region of 5.3 ppm. On the other hand, the variation of polymer molecular mass causes a slight change in chemical shift of the peaks and the multiplet appearance as a result, which is evident in all the polymer peaks, including the expanded peak of 5.3 ppm. Therefore, there was no indication of the doublet of doublet peaks of phenyllactic acid reactant. In the same way, for hydrogens (b), the increase in the peak range to 2.5-3.5 ppm compared to phenyllactic acid (3-3.5 ppm) and also the splitting of doublet of doublet peaks into the multiplets, indicates the synthesis of polymer. The area under peaks were obtained based on the terminal hydrogen (a) peak (4 ppm, integral = 1), which confirmed the hydrogens ratio and polyphenyllactide structure. The singlet peak of 13 ppm showed the terminal carboxyl group of polymers. FIG. 2F illustrates the Gel permeation chromatography (GPC) spectrum 214 of polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure. Polyphenyllactide was not fully dissolved in Tetrahydrofuran (THF) and precipitated. Therefore, the averageRef- 1403-02-8765 molecular mass of polyphenyllactide dissolved in THF was calculated by GPC method, and MW = 7.87 x 103Da and the polydispersity index, PDI = 1.64, was obtained.

[0073] In further detail with respect to step 104, step 104 may include producing oligo(kojic-co-gluconic acid). In an exemplary embodiment, oligo(kojic-co-gluconic acid) may be produced by reacting kojic acid with gluconic acid in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. In an exemplary embodiment, details of step 104 for reacting kojic acid with gluconic acid are described in context of elements presented in FIG. 3A. FIG. 3A illustrates exemplary reaction scheme 300 for producing oligo(kojic-co- gluconic acid) 302, consistent with one or more exemplary embodiments of the present disclosure. In further detail with respect to exemplary reaction scheme 300, oligo(kojic-co- gluconic acid) 302 may be formed by reacting kojic acid 304 with gluconic acid 306. In an exemplary embodiment, details of step 104 for producing oligo(kojic-co-gluconic acid) are described in context of elements presented in FIG. 3B. FIG. 3B illustrates an exemplary method of step 104 for producing oligo(kojic-co-gluconic acid), consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, an exemplary method 104 may comprise: forming an exemplary melted mixture comprising oligo(kojic-co-gluconic acid) (step 308); forming an exemplary yellow solid comprising oligo(kojic-co-gluconic acid) (step 310); forming an exemplary pure precipitate of oligo(kojic-co-gluconic acid) (step 312); and drying an exemplary washed pure precipitate of oligo(kojic-co-gluconic acid) (step 314).

[0074] In further detail with respect to step 308, step 308 may include forming an exemplary melted mixture comprising oligo(kojic-co-gluconic acid). In an exemplary embodiment, forming an exemplary melted mixture comprising oligo(kojic-co-gluconic acid) may comprise mixing / stirring kojic acid with gluconic acid at a predeterminedRef- 1403-02-8765 temperature level, for a predetermined time duration, under vacuum, and in a presence of exemplary catalysts. In an exemplary embodiment, mixing / stirring kojic acid with gluconic acid at a predetermined temperature level, for a predetermined time duration, under vacuum, and in a presence of exemplary catalysts may comprise mixing / stirring kojic acid (e.g., in form of freeze-dried powder) with gluconic acid (e.g., in form of freeze-dried powder) with a molar ratio of 1: 1 (kojic acid: gluconic acid) on a stirrer at a temperature level between 110 °C and 130 °C, for a time duration of between 25 minutes and 35 minutes, under vacuum using a vacuum, and in a presence of exemplary catalysts comprising tin(II) octoate and zinc chloride with a final concentration of 1% w / w individually. For example, in an exemplary embodiment, to prepare an exemplary melted mixture comprising oligo(kojic-co-gluconic acid), about 1 mol of an exemplary freeze dried powder of kojic acid, about 1 mol of an exemplary freeze dried powder of gluconic, tin(II) octoate and zinc chloride with a final concentration of 1% w / w individually may be added (using e.g., spatula) to an exemplary laboratory container (e.g., crystal vial), then placed in an exemplary reaction place (e.g., reaction capsule) and stirred — using a magnetic stirrer — at about 120 °C, at a pressure level of 140 bar under vacuum using a vacuum, and for a time duration of about 30 minutes.

[0075] In further detail with respect to step 310, step 310 may include forming an exemplary yellow solid comprising oligo(kojic-co-gluconic acid). In an exemplary embodiment, forming an exemplary yellow solid comprising oligo(kojic-co-gluconic acid) may comprise cooling an exemplary melted mixture (i.e., an exemplary melted mixture set forth in step 308) to a predetermined temperature level. In an exemplary embodiment, cooling an exemplary melted mixture (i.e., an exemplary melted mixture set forth in step 308) to a predetermined temperature level may include cooling an exemplary melted mixture (i.e., an exemplary melted mixture set forth in step 308) to a predetermined temperature level of 25Ref- 1403-02-8765°C. In an exemplary embodiment, an exemplary melted mixture may be cooled to a predetermined temperature level of 25 °C by using an exemplary cold bath.

[0076] In further detail with respect to step 312, step 312 may include forming an exemplary pure precipitate of oligo(kojic-co-gluconic acid). In an exemplary embodiment, forming an exemplary pure precipitate of oligo(kojic-co-gluconic acid) may comprise removing excess amounts of kojic acid and gluconic acid from an exemplary yellow solid. In an exemplary embodiment, removing excess amounts of kojic acid and gluconic acid from an exemplary yellow solid may comprise washing an exemplary yellow solid twice with double distilled water at a temperature level between 22 °C and 25 °C, and then filtering through an exemplary filter paper.

[0077] In further detail with respect to step 314, step 314 may include drying an exemplary washed pure precipitate of oligo(kojic-co-gluconic acid). In an exemplary embodiment, drying an exemplary washed pure precipitate of oligo(kojic-co-gluconic acid) may comprise heating an exemplary washed pure precipitate of oligo(kojic-co-gluconic acid) to a predetermined temperature level. In an exemplary embodiment, heating an exemplary washed pure precipitate of oligo(kojic-co-gluconic acid) to a predetermined temperature level may comprise heating an exemplary washed pure precipitate of oligo(kojic-co-gluconic acid) to a predetermined temperature level of 40 °C by using an exemplary oven. In an exemplary embodiment, the dried form of an exemplary pure form of oligo(kojic-co-gluconic acid) may be stored at a temperature level of -20 °C in an exemplary closed container. FIG. 3C illustrates anNMR spectrum 316 of kojic acid, consistent with one or more exemplary embodiments of the present disclosure. First, theNMR spectrum of reactants was investigated to determine the structure. Kojic acid in DMSO contains three singlet hydrogen peaks in the regions of 4.3, 6.3 and 8 ppm, which correspond to the (a) and (b) hydrogens attached to ring and two hydrogens of methylene (c), respectively. The ring attachedRef- 1403-02-8765 hydrogens have no neighboring hydrogens, so they appeared as a singlet peak and they had more chemical shift than methylene hydrogens due to their proximity to the double bond. Methylene hydrogens are also symmetric and equivalent due to the achiral carbon and hydroxyl group (e). So, they were observed as a singlet peak at 3.4 ppm. In the region of 5.7 and 9 ppm, the methylene hydroxyl (e) and the ring hydroxyl (d) were seen as a singlet peak respectively. The ring hydroxyl peak is deshielded due to the electron withdrawing double bonds and carbonyl which results in acidic properties and appeared at 9 ppm. Therefore, this molecule is called kojic acid (pKa = 9.4). The calculation of area under the peaks based on the hydrogen peak (a) (integral = 1) confirmed the number and ratio of all hydrogens. Based on this, the area under peak (c) is twice of other peaks. FIG. 3D illustrates anNMR spectrum 318 of gluconic acid, consistent with one or more exemplary embodiments of the present disclosure. Gluconic acid is the oxidized form of glucose and has six carbons, five hydroxyls and one carboxyl, and is in equilibrium with its lactone form. TheNMR spectrum of freeze-dried gluconic acid in DMSO contains a wide range of multiplet hydrogen and singlet hydroxyl peaks in the range of 3-6.5 ppm. At 12.5 ppm, the carboxyl singlet peak is also observed. FIG. 3E illustrates anNMR spectrum 320 of oligo(kojic-co-gluconic acid) and kojic acid, consistent with one or more exemplary embodiments of the present disclosure. FIG. 3F illustrates anNMR spectrum 322 of oligo(kojic-co-gluconic acid), consistent with one or more exemplary embodiments of the present disclosure. Both kojic acid and gluconic acid molecules are soluble in water. In order to purify oligo(kojic-co- gluconic acid) after reaction, the product was stirred twice in water and the sediment was fdtered and dried in an oven at 40 °C and theNMR spectrum was compared with reactants in DMSO. The entire kojic acid hydrogens were observed with changes confirming the reaction. The hydrogen (a) singlet peak at 8 ppm was chosen as the basis of integration (integral = 1). The hydrogen (b) singlet peak with an integral of one appeared at 6.6 ppm.Ref- 1403-02-8765The peak of methylene hydrogens (c) at 4.4 ppm was observed as a doublet with a coupling constant of 6.2 Hz and an integral of two. The splitting of peak (c) into doublet, indicates the reaction of methylene hydroxyl (e) in kojic acid with gluconic acid, because the methylene hydrogens (c) become asymmetric and nonequivalent after reaction and coupling with each other. On the other hand, the shift of singlet hydroxyl (e) from 5.7 ppm to 6.4 ppm and the decrease of underneath area to 0.4, also confirmed the reaction. The integral of ring hydroxyl (d) singlet peak at 9 ppm also decreased to 0.4, which indicated the reaction on both sides of kojic acid. It can be concluded from the area under peaks (d) and (e) (integral = 0.4), that every two kojic acid molecules have reacted through one hydroxyl group (d) and one hydroxyl group (e). So, the other hydroxyl groups (d) and (e) are also free. In other words, the 1:2 ratio of hydroxyl (d) or (e) to hydrogen (a) in kojic acid means the esterification of two kojic acid molecules from two opposite sides with one gluconic acid. The comparison of 3-6.5 ppm range of the1H NMR spectrum of oligo(kojic-co-gluconic acid) with gluconic acid spectrum indicated a decrease in the number of gluconic acid peaks, which proofs the reaction. The triplet peak with J = 6.1 Hz at 5.8 ppm, and similar integral to the peak of hydrogen (a) in kojic acid (integral base peak = 1) confirmed the presence of two symmetric hydrogens (B) and (C) in the gluconic acid, since hydrogens (B) and (C) have two hydrogens on the neighboring carbons and their peak appears as a triplet. In terms of the number, two hydrogens (B) and (C) in gluconic acid are equal to one hydrogen (a) in two kojic acid molecules. On the other hand, the doublet peak at 4.3 ppm with the integral of one, represents two equivalent hydrogens (E), which are adjacent to one hydrogen and appeared as a doublet with J = 6.1 Hz. In terms of the number, two equivalent hydrogens (E) in gluconic acid are equal to one hydrogen (a) in two kojic acid molecules. The similar coupling constant of triplet peak (C) and doublet peak (E) is due to the common neighboring hydrogen (D). The hydrogens (E) have less chemical shift than hydrogens (B) and (C) due to more electronRef- 1403-02-8765 density (shielded). In the region of 5.7 ppm and 4.5 ppm, the peak of hydrogen (D) and hydrogen (A) with an integral of 0.4 and 0.3 are observed respectively, which are almost half of the hydrogen (a) in two kojic acid molecules. At 12.5 ppm, the lack of gluconic carboxyl peak indicated the reaction through this functional group, consequently, a trimer was created by reaction of two kojic acid molecules with the carboxyl and alpha hydroxyl of gluconic acid. The higher reactivity of alpha hydroxyl compared to other gluconic acid hydroxyls is logical due to its proximity to the electron withdrawing carbonyl group. Thus, the ratio of hydroxyl groups to oligomer mass decreases by reaction progress, which results in water solubility reduction and oligomer precipitation.

[0078] In further detail with respect to step 106, step 106 may include linking oligo(kojic- co-gluconic acid) to polyphenyllactide. In an exemplary embodiment, linking oligo(kojic-co- gluconic acid) to polyphenyllactide may be performed by reacting polyphenyllactide with oligo(kojic-co-gluconic acid). In an exemplary embodiment, details of step 106 for reacting polyphenyllactide with oligo(kojic-co-gluconic acid) are described in context of elements presented in FIG. 4A. FIG. 4A illustrates exemplary reaction scheme 400 for linking oligo(kojic-co-gluconic acid) 402 to polyphenyllactide 404, consistent with one or more exemplary embodiments of the present disclosure. In further detail with respect to exemplary reaction scheme 400, linking oligo(kojic-co-gluconic acid) to polyphenyllactide may be performed by reacting polyphenyllactide 404 with oligo(kojic-co-gluconic acid) 402 at an exemplary temperature level between 110 °C and 130 °C, which may result in forming poly(PLKGA) 406. In an exemplary embodiment, details of step 106 for linking oligo(kojic- co-gluconic acid) to polyphenyllactide are described in context of elements presented in FIG. 4B. FIG. 4B illustrates an exemplary method of step 106 for linking oligo(kojic-co-gluconic acid) to polyphenyllactide, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, an exemplary method 106 may comprise:Ref- 1403-02-8765 forming an exemplary first solution comprising an exemplary diphenyl ether solution of polyphenyllactide (step 408); cooling an exemplary first solution to a predetermined temperature level (step 410); forming an exemplary second solution comprising an exemplary diphenyl ether solution of poly(PLKGA) (step 412); cooling an exemplary second solution to a predetermined temperature level (step 414); forming an exemplary precipitate of poly(PLKGA) (step 416); washing an exemplary precipitate of poly(PLKGA) (step 418); and drying an exemplary washed precipitate (step 420).

[0079] In further detail with respect to step 408, step 408 may include forming an exemplary first solution comprising an exemplary diphenyl ether solution of polyphenyllactide. In an exemplary embodiment, forming an exemplary first solution comprising an exemplary diphenyl ether solution of polyphenyllactide may comprise forming an exemplary first solution comprising an exemplary diphenyl ether solution of polyphenyllactide with a concentration between 240 mg / ml and 260 mg / ml. In an exemplary embodiment, an exemplary first solution comprising an exemplary diphenyl ether solution of polyphenyllactide with a concentration between 240 mg / ml and 260 mg / ml may be prepared by dissolving polyphenyllactide (e.g., in a form of a solid) in a diphenyl ether solution (e.g., a diphenyl ether solution with a concentration of at least 95% (v / v)) on a stirrer (e.g., a magnetic stirrer) at a temperature level between 150 °C and 170 °C, under reflux. For example, in an exemplary embodiment, to prepare about 2 mL of an exemplary first solution, about 500 mg powder of polyphenyllactide may be added to about 2 mL of diphenyl ether solution (e.g., with a concentration of at least 95% (v / v)), in an exemplary laboratory container (e.g., a beaker, flask, etc.), and may be stirred — using a magnetic stirrer — at about 160° C, under reflux.

[0080] In further detail with respect to step 410, step 410 may include cooling an exemplary first solution to a predetermined temperature level. In an exemplary embodiment,Ref- 1403-02-8765 cooling an exemplary first solution to a predetermined temperature level may comprise cooling an exemplary first solution to a predetermined temperature level of 110 °C. In an exemplary embodiment cooling an exemplary first solution to a predetermined temperature level of 110 °C may comprise placing an exemplary first solution in an exemplary cooling system (e.g., a cold bath).

[0081] In further detail with respect to step 412, step 412 may include forming an exemplary second solution comprising an exemplary diphenyl ether solution of poly(PLKGA). In an exemplary embodiment, forming an exemplary second solution comprising an exemplary diphenyl ether solution of poly(PLKGA) may comprise adding an exemplary powder of pure oligo(kojic-co-gluconic acid) (i.e., an exemplary powder of an exemplary pure oligo(kojic-co-gluconic acid) set forth in step 104) with a concentration of 10% w / w (with respect to the weight of polyphenyllactide) to an exemplary cooled first solution on a stirrer (e.g., a magnetic stirrer) at a temperature level between 105 °C and 115 °C and stirring for a time duration of about 9 minutes and 12 minutes. In an exemplary embodiment, an exemplary second solution may have a colour of yellow. For example, in an exemplary embodiment, to prepare an exemplary second solution comprising poly(PLKGA), an exemplary powder of an exemplary pure oligo(kojic-co-gluconic acid) with a concentration of (10% w / w) (with respect to the weight of polyphenyllactide) may be added to an exemplary cooled first solution on a stirrer (e.g., a magnetic stirrer) at a temperature level of 110 °C and stirred for a time duration of 10 minutes.

[0082] In further detail with respect to step 414, step 414 may comprise cooling an exemplary second solution to a predetermined temperature level. In an exemplary embodiment, cooling an exemplary second solution to a predetermined temperature level may comprise cooling an exemplary second solution to a predetermined temperature level of 25 °C. In an exemplary embodiment, cooling an exemplary second solution to aRef- 1403-02-8765 predetermined temperature level of 25 °C may comprise placing an exemplary second solution in an exemplary cooling system (e.g., cold bath).

[0083] In further detail with respect to step 416, step 416 may include forming an exemplary precipitate of poly(PLKGA). In an exemplary embodiment, forming an exemplary precipitate of poly(PLKGA) may include adding an exemplary anti- solvent to an exemplary cooled second solution with a predetermined volume ratio of 1:10 (an exemplary cooled second solution: an exemplary anti- solvent). In an exemplary embodiment, an exemplary anti- solvent may comprise an exemplary ethanol solution. In an exemplary embodiment, adding an exemplary anti- solvent to an exemplary cooled second mixture with a predetermined volume ratio of 1:10 (an exemplary cooled second solution: an exemplary anti-solvent) may comprise adding an exemplary anti-solvent comprising ethanol solution (e.g., with a concentration of at least 95% (v / v)) (e.g., using graduated cylinder) to an exemplary cooled second solution with a predetermined volume ratio of 1: 10 (an exemplary cooled second solution: an exemplary ethanol solution).

[0084] In further detail with respect to step 418, step 418 may include washing an exemplary precipitate of poly(PLKGA). In an exemplary embodiment, washing an exemplary precipitate of poly(PLKGA) may include washing an exemplary precipitate of poly(PLKGA) by an exemplary solvent. In an exemplary embodiment, washing am exemplary precipitate of poly(PLKGA) by an exemplary solvent may include washing an exemplary precipitate of poly(PLKGA) by an exemplary solvent comprising ethanol solution (e.g., with a concentration of at least 95% (v / v)).

[0085] In further detail with respect to step 420, step 420 may include drying an exemplary washed precipitate. In an exemplary embodiment, drying an exemplary washed precipitate may comprise drying an exemplary washed precipitate at a predetermined temperature level. In an exemplary embodiment, drying an exemplary washed precipitate ofRef- 1403-02-8765 poly(PLKGA) at a predetermined temperature level of 40 °C in an exemplary oven. In an exemplary embodiment, drying an exemplary washed precipitate may result in forming an exemplary dried powder of poly(PLKGA). FIG. 4C illustrates the comparison of!H NMR spectra 422 of polyphenyllactide (right) and poly(PLKGA) (left), consistent with one or more exemplary embodiments of the present disclosure. FIG. 4D illustrates the!H NMR spectrum 424 of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure. After reaction of oligo(kojic-co-gluconic acid) with polyphenyllactide and purifying the copolymer, the!H NMR spectrum in dimethylsulfoxide (DMSO) was compared with the polyphenyllactide spectrum in order to determine the structure. Polyphenyllactide carboxyl group may react with two hydroxyls of kojic acid and four hydroxyls of gluconic acid in the oligo(kojic-co-gluconic acid) structure. In the 5.5 ppm region of poly(PLKGA)!H NMR spectrum, the splitting of hydrogens (B) and (C) triplet peak into a multiplet peak, indicated the reaction of polyphenyllactide with the hydroxyls of gluconic acid and change of symmetry. This reaction also changed the symmetry and equivalency of hydrogens (E) which was realized by splitting of hydrogens (E) doublet peak into a multiplet peak. The probability of polyphenyllactide reaction with gluconic terminal hydroxyl is higher than other hydroxyls due to the less steric hindrance. At 4 ppm, the doublet peak of kojic acid methylene (-CH2-) was observed, which indicates the structure stability of oligo(kojic-co-gluconic acid) during the reaction, and the coupling constant change from 6.2 Hz to 10.3 Hz showed polymer binding. In the region of 6.1-6.5 ppm, two singlet peaks with an integral of 0.04 and in the region of 8.1-8.7 ppm, two singlet peaks with an integral of 0.04 are observed, the sum of which is equal to the area under methylene peak. Therefore, hydrogen (a) of kojic acid appeared as two peaks in the region of 8.1-8.7 ppm and hydrogen (b) of kojic acid also appeared as two peaks in the region of 6.1-6.5 ppm. In the region of 6.1-6.5 ppm, the kojic acid hydroxyl (e) peak was not seen, and the two peaks in 9.6 ppm and 10 ppm belongs toRef- 1403-02-8765 kojic acid hydroxyl (d). Therefore, polyphenyllactide reacted with kojic acid from the methylene side due to less steric hindrance, and according to area under the 10 ppm peak, the kojic acid ring hydroxyl (d) had less reaction with polyphenyllactide. On the other hand, the lack of polyphenyllactide terminal carboxyl singlet peak at 13 ppm, also confirmed the reaction. Finally, the appearance of hydrogens (a) and hydrogens (b) peaks in two different chemical shifts also confirmed the difference in reaction site.

[0086] In further detail with respect to step 108, step 108 may include forming an exemplary nano-colloid suspension of poly(PLKGA). In an exemplary embodiment, details of step 108 for forming an exemplary nano-colloid suspension of poly(PLKGA) are described in context of elements presented in FIG. 5. FIG. 5 illustrates an exemplary method of step 108 for forming an exemplary nano-colloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, an exemplary method 108 may comprise: forming an exemplary DMSO solution of poly(PLKGA) (step 500); diluting an exemplary DMSO solution of poly(PLKGA) (step 502); and forming an exemplary milky colloid suspension comprising poly(PLKGA) nanoparticles with a concentration of 1 mg / ml (step 504).

[0087] In further detail with respect to step 500, step 500 may include forming an exemplary DMSO solution of poly(PLKGA). In an exemplary embodiment, forming an exemplary DMSO solution of poly(PLKGA) may comprise forming an exemplary DMSO solution of poly(PLKGA) with a concentration of 50 mg / ml (with respect to the volume of an exemplary DMSO solution of poly(PLKGA)). In an exemplary embodiment, forming an exemplary DMSO solution of poly(PLKGA) with concentration of 50 mg / ml may comprise adding an exemplary dried powder of poly(PLKGA) (i.e., an exemplary dried powder of poly(PLKGA) set forth in step 106) to an exemplary DMSO solution (e.g., with a concentration of at least 95% (v / v)). For example, to prepare 1ml of an exemplary DMSORef- 1403-02-8765 solution of poly(PLKGA), 50 mg of an exemplary powder of dried powder of poly(PLKGA) may be added to about 1 ml of an exemplary DMSO solution (e.g., with a concentration of at least 95% (v / v)) using spatula, in an exemplary laboratory container (e.g., a beaker, flask, etc.), while stirred-on a magnetic stirrer- at a temperature level of 25 °C.

[0088] In further detail with respect to step 502, step 502 may include diluting an exemplary DMSO solution of poly(PLKGA). In an exemplary embodiment, diluting an exemplary DMSO solution of poly(PLKGA) may comprise adding an exemplary organic solvent to an exemplary DMSO solution of poly(PLKGA). In an exemplary embodiment, adding an exemplary organic solvent to an exemplary DMSO solution of poly(PLKGA) may comprise adding an exemplary organic solvent comprising ethanol solution (e.g., with a concentration of at least 95% (v / v)) to an exemplary DMSO solution of poly(PLKGA) with a volume ratio of 1:4 (an exemplary DMSO solution of poly(PLKGA): an exemplary organic solvent comprising ethanol solution). In an exemplary embodiment, an exemplary diluted DMSO solution of poly(PLKGA) may have a concentration of about 10 mg / ml. For example, in an exemplary embodiment, to prepare about 5ml of an exemplary diluted DMSO solution of poly(PLKGA), about 4 ml of an exemplary solution comprising ethanol (e.g., with a concentration of at least 95% (v / v)) may be added (e.g., using a graduated cylinder) to 1 ml of an exemplary DMSO solution of poly(PLKGA), while stirred on a magnetic stirrer at a temperature level of 25 °C in an exemplary laboratory container (e.g., a beaker, flask, etc.).

[0089] In further detail with respect to step 504, step 504 may include forming an exemplary milky colloid suspension comprising poly(PLKGA) nanoparticles with a concentration of 1 mg / ml. In an exemplary embodiment, forming an exemplary milky colloid suspension comprising 1 mg / ml poly(PLKGA) nanoparticles may comprise adding an exemplary diluted DMSO solution of poly(PLKGA) drop wise to distilled water. In an exemplary embodiment, adding an exemplary diluted DMSO solution of poly(PLKGA)Ref- 1403-02-8765 drop wise to distilled water may comprise adding an exemplary diluted DMSO solution of poly(PLKGA) with a volume ratio of 1:9 (an exemplary diluted DMSO solution of poly(PLKGA): distilled water) dropwise to distilled water while stirring. For example, in an exemplary embodiment, to prepare an exemplary milky colloid suspension comprising 1 mg / ml of poly(PLKGA) nanoparticles, about 5 ml of an exemplary diluted DMSO solution of poly(PLKGA) may be added dropwise to 45 ml of distilled water, while stirred on a magnetic stirrer at a temperature level of 25 °C in an exemplary laboratory container (e.g., a beaker, flask, etc.).

[0090] An exemplary embodiment is directed to an exemplary anti-neoplastic and antibacterial composition. In an exemplary embodiment, an exemplary anti-neoplastic and antibacterial composition may comprise an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38. In an exemplary embodiment, an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise poly(PLKGA) and SN-38 with a weight ratio of 100: 1 (poly(PLKGA):SN-38). In an exemplary embodiment, an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise an exemplary dispersed phase and an exemplary continuous phase. In an exemplary embodiment, an exemplary dispersed phase may comprise poly(PLKGA) bound SN-38 nanoparticles. In an exemplary embodiment, each exemplary nanoparticle of poly(PLKGA) bound SN-38 may be coated with polyvinyl alcohol (with a molecular weight between 30-70 kDa). In an exemplary embodiment, an exemplary continuous phase may comprise an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38. In an exemplary embodiment, an exemplary medium of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise an exemplary biocompatible hydrophilic fluid. In an exemplary embodiment, an exemplary biocompatible hydrophilic fluid may comprise water and sorbitol. In an exemplary embodiment, the biocompatible hydrophilic fluid fills the space between the poly(PLKGA)Ref- 1403-02-8765 bound SN-38 nanoparticles. “Anti -neoplastic” or “anti-cancer” or “cytotoxic” or “hazardous” composition may refer to a group of pharmaceutical agents that act to prevent, inhibit, or halt the development of a neoplasm (a tumor).

[0091] Liposomal carriers are FDA approved for encapsulation and delivery of water- soluble drugs in chemotherapy due to their thin double-layer membrane and large aqueous core. Encapsulation of hydrophobic chemotherapeutic s in liposome membrane is not rational because of the small membrane and early drug release. Due to the lipophilic nature of most chemotherapy drugs such as bleomycin, vincristine, vinblastine, paclitaxel, docetaxel, bendamustine, gemcitabine, fludarabine and etoposide, a lipophilic carrier with a nanocolloidal structure can eliminate the need of derivatization and ionization of chemotherapeutic s for solubility. An example is the hydrophobic 7-Ethyl-10- hydroxycamptothecin (SN-38), which is modified by addition of piperidine and ionized to hydrochloride salt to produce water soluble drug, irinotecan. Therefore, the potency of irinotecan is reduced to a hundredth of SN-38 and requires a higher therapeutic dose, which leads to more side effects. The lipophilic poly(PLKGA) nano-colloid may dissolve SN-38 and synergistically increase the therapeutic effect by the inherent anti-neoplastic activity of the monomers, while reduces drug resistance and side effects.

[0092] Referring to the figures, FIG. 6 illustrates an exemplary flowchart of exemplary method 600 for producing an exemplary anti-neoplastic and anti-bacterial composition comprising an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38, consistent with one or more exemplary embodiments of the present disclosure. In an exemplary embodiment, exemplary method 600 may include: forming an exemplary DMSO solution of SN-38 (step 602); forming an exemplary DMSO solution of poly(PLKGA) (step 604); forming an exemplary DMSO solution comprising SN-38 and poly(PLKGA) (step 606); diluting an exemplary DMSO solution comprising SN-38 and poly(PLKGA) (step 608);Ref- 1403-02-8765 forming an exemplary organic solution comprising SN-38 and poly(PLKGA) (step 610); forming an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38 (step 612); forming an exemplary hydrophilic layer on poly(PLKGA) bound SN-38 nanoparticles (step 614); forming an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles (step 616), and forming an exemplary stable nano-colloid suspension of poly(PLKGA) bound SN-38 (step 618).

[0093] In further detail with respect to step 602, step 602 may include forming an exemplary DMSO solution of SN-38. In an exemplary embodiment, forming an exemplary DMSO solution of SN-38 may include forming an exemplary DMSO solution of SN-38 with a concentration between 9 mg / ml and 11 mg / ml. In an exemplary embodiment, forming an exemplary DMSO solution of SN-38 with a final concentration between 9 mg / ml and 11 mg / ml may comprise adding SN-38 (e.g., in form of solid) to a DMSO solution (e.g., a DMSO solution with a concentration of at least 95% (v / v)). For example, in an exemplary embodiment, to prepare about 1ml of an exemplary DMSO solution of SN-38, about 10 mg of SN-38 (e.g., in form of solid) may be added to about 1 mL of DMSO solution (e.g., with a concentration of at least 95% (v / v)), using spatula, in an exemplary laboratory container (e.g., a beaker, flask, etc.), and may be stirred-using a magnetic stirrer-at about 25 °C.

[0094] In further detail with respect to step 604, step 604 may include forming an exemplary DMSO solution of poly(PLKGA). In an exemplary embodiment, forming an exemplary DMSO solution of poly(PLKGA) may include forming an exemplary DMSO solution of poly(PLKGA) with a concentration between 90 mg / ml and 110 mg / ml. In an exemplary embodiment, forming an exemplary DMSO solution of poly(PLKGA) with a concentration between 90 mg / ml and 110 mg / ml may comprise adding poly(PLKGA) (e.g., in form of solid) to a DMSO solution (e.g., a DMSO solution with a concentration of at least 95% (v / v)). For example, in an exemplary embodiment, to prepare 1 ml of an exemplaryRef- 1403-02-8765DMSO solution of poly(PLKGA), 100 mg of poly(PLKGA) may be added to about 1 ml DMSO solution (e.g., with a concentration of at least 95% (v / v)), using spatula, in an exemplary laboratory container (e.g., a beaker, flask, etc.).

[0095] In further detail with respect to step 606, step 606 may include forming an exemplary DMSO solution comprising SN-38 and poly(PLKGA). In an exemplary embodiment, forming an exemplary DMSO solution comprising SN-38 and poly(PLKGA) may comprise adding an exemplary DMSO solution of SN-38 (i.e., an exemplary DMSO solution of SN-38 set forth in step 602) to an exemplary DMSO solution of poly(PLKGA) with a predetermined weight ratio. In an exemplary embodiment, adding an exemplary DMSO solution of SN-38 to an exemplary DMSO solution of poly(PLKGA) may comprise adding an exemplary DMSO solution of SN-38 (i.e., an exemplary DMSO solution of SN- 38 set forth in step 602) to an exemplary DMSO solution of poly(PLKGA) with a predetermined weight ratio of 12.5: 1 (an exemplary DMSO solution of poly(PLKGA): an exemplary DMSO solution of SN-38) in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc. For example, to prepare an exemplary DMSO solution comprising SN-38 and poly(PLKGA), about 0.8 ml of an exemplary DMSO solution of SN-38 with a concentration of 10 mg / ml may be added to about 1 ml of an exemplary DMSO solution of poly(PLKGA) with a concentration of 100 mg / ml in an exemplary laboratory container (e.g., beaker, flask, etc.), and may be stirred-using a magnetic stirrer- a temperature level of 25 °C.

[0096] In further detail with respect to step 608, step 608 may include diluting an exemplary DMSO solution comprising SN-38 and poly(PLKGA). In an exemplary embodiment, diluting an exemplary DMSO solution comprising SN-38 and poly(PLKGA) may comprise adding an exemplary DMSO solution (e.g., an DMSO solution with a concentration of at least 95% (v / v)) to an exemplary DMSO solution comprising SN-38 andRef- 1403-02-8765 poly(PLKGA) (i.e., an exemplary DMSO solution comprising SN-38 and poly(PLKGA) set forth in step 606) to reach a DMSO solution of poly(PLKGA) with a final concentration between 40 mg / ml and 60 mg / ml (with respect to the final concentration of an exemplary DMSO solution of poly(PLKGA)) in an exemplary laboratory container including, but not limited to, beakers, tins, flasks, bottles, buckets, basins, bowls, vials, tubes, barrels, cannisters, etc.

[0097] In further detail with respect to step 610, step 610 may include forming an exemplary organic solution comprising SN-38 and poly(PLKGA). In an exemplary embodiment, forming an exemplary organic solution comprising SN-38 and poly(PLKGA) may comprise adding an exemplary ethanol solution (e.g., an ethanol solution with a concentration of at least 95% (v / v)) to an exemplary diluted DMSO solution comprising SN- 38 and poly(PLKGA) with a predetermined volume ratio. In an exemplary embodiment, adding an exemplary ethanol solution (e.g., an ethanol solution with a concentration of at least 95% (v / v)) to an exemplary diluted DMSO solution comprising SN-38 and poly(PLKGA) with a predetermined volume ratio may comprise adding an exemplary ethanol solution (e.g., an ethanol solution with a concentration of at least 95% (v / v)) to an exemplary diluted DMSO solution comprising SN-38 and poly(PLKGA) with a predetermined volume ratio of at least 4: 1 (ethanol: DMSO). In an exemplary embodiment, adding an exemplary ethanol solution (e.g., an ethanol solution with a concentration of at least 95% (v / v)) to an exemplary diluted DMSO solution comprising SN-38 and poly(PLKGA) with a predetermined volume ratio of at least 4: 1 (ethanol: DMSO) may comprise adding an exemplary ethanol solution (e.g., an ethanol solution with a concentration of at least 95% (v / v)) to an exemplary diluted DMSO solution comprising SN-38 and poly(PLKGA) (i.e., an exemplary diluted DMSO solution comprising SN-38 and poly(PLKGA) set forth in step 608) with a predetermined volume ratio of at least 4: 1Ref- 1403-02-8765(ethanol: DMSO) while stirring e.g., using a magnetic stirrer, in a laboratory container (e.g., beaker, flask, etc.), at a temperature level of 25 °C.

[0098] In further detail with respect to step 612, step 612 may include forming an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38. In an exemplary embodiment, forming an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise adding an exemplary organic solution (i.e., an exemplary organic solution set forth in step 610) dropwise to distilled water with a volume ratio of 1:9 (an exemplary organic solution: distilled water) while stirring-e.g., using a magnetic stirrer, in a laboratory container (e.g., beaker, flask, etc.), at a temperature level of 25 °C.

[0099] In further detail with respect to step 614, step 614 may include forming an exemplary hydrophilic layer on poly(PLKGA) bound SN-38 nanoparticles. In an exemplary embodiment, forming an exemplary hydrophilic layer on poly(PLKGA) bound SN-38 nanoparticles may comprise adding an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 (i.e., an exemplary nano-colloid suspension set forth in step 612) to an exemplary water solution comprising 5% w / v sorbitol and 1% w / v polyvinyl alcohol with a volume ratio of 1: 1 (an exemplary nano-colloid suspension: an exemplary water solution), while stirring e.g., using a magnetic stirrer, in a laboratory container (e.g., beaker, flask, etc.), at a temperature level of 25 °C.[000100] In further detail with respect to step 616, step 616 may include forming an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles. In an exemplary embodiment, forming an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles may comprise centrifuging an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38 at a predetermined speed and for a predetermined time duration. In an exemplary embodiment, centrifuging an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38 at a predetermined speed and for a predeterminedRef- 1403-02-8765 time duration may comprise centrifuging an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38 (i.e., an exemplary white nano-colloid suspension set forth in step 614) at a predetermined speed of 10000 rpm and for a predetermined time duration of 10 minutes. In an exemplary embodiment, centrifuging an exemplary white nano-colloid suspension of poly(PLKGA) bound SN-38 poly(PLKGA) may result in forming an exemplary supernatant comprising water, DMSO, ethanol and free SN-38. In an exemplary embodiment, an exemplary supernatant may be discarded and an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles may be extracted.[000101] In further detail with respect to step 618, step 618 may include forming an exemplary stable nano-colloid suspension of poly(PLKGA) bound SN-38. In an exemplary embodiment, forming an exemplary stable nano-colloid suspension of poly(PLKGA) bound SN-38 may comprise adding distilled water to an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles (i.e., an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles set forth in step 616). In an exemplary embodiment, adding distilled water to an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles (i.e., an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles set forth in step 616) may comprise adding distilled water to an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles (i.e., an exemplary precipitate comprising poly(PLKGA) bound SN-38 nanoparticles set forth in step 616) while stirring, at a temperature level of 25 °C.EXAMPLES[000102] Hereinafter, one or more exemplary embodiments will be described in further detail with reference to examples. It will be obvious to a person having ordinary skill in the art that these examples may be for illustrative purposes only and are not to be interpreted to limit the scope of one or more exemplary embodiments.Ref- 1403-02-8765Example 1: Evaluation of the anti-microbial activity of an exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly (phenyllactic-co-kojic-co-gluconic acid) (poly(PLKGA))[000103] At first, Mueller Hinton Broth (MHB) medium was used to prepare serial dilutions of an exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA) (0.125-4 mg / ml). Next, two replicates of 180 pl of each concentration were put into a 96-well plate, and 20 pl of the bacterial suspension (106CFU / ml in 0.9% sodium chloride) was added. Gram-positive (Staphylococcus aureus 1112, 43300, and 1114), Gram-negative (Escherichia coli 1330, Pseudomonas aeruginosa 1074, and Pseudomonas aeruginosa PAO1), and yeast (Candida albicans 5027) microorganisms were used in this test. Subsequently, the 96-well plate was incubated for 24 hours at 37 °C. Subsequently, each well was filled with 20 pl of a 5 mg / ml solution of triphenyl tetrazolium chloride (TTC) in distilled water, and left in the incubator for three hours. Therefore, the chemical is converted by active microorganisms to triphenyl formazan (TPF), which is red and correlated with the number of microbes; that is, the less red color produced, the more microbes were suppressed. Therefore, the lowest inhibitory concentration (MIC) was determined by looking at the first well that was red-color-free. After another 24 hours in the incubator, the plate was taken out to find the lowest bactericidal concentration (MBC), which was defined as the lowest concentration that did not contain any red color.[000104] The results of MIC and MBC tests demonstrated antibacterial activity of exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA) (0.125-4 mg / ml) against gram-negative bacteria, Pseudomonas aeruginosa 1074, and gram-positive bacteria, Staphylococcus aureus and Staphylococcus epidermidis. On the other hand, they showed no inhibitory impact on gram-negative bacteria, Escherichia coli, and Pseudomonas aeruginosa PAO1 and Candida albicans yeast.Ref- 1403-02-8765Consequently, exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA) did not exhibit chemical toxicity and instead displayed biological toxicity in the 0.125-4 mg / ml range. Pseudomonas aeruginosa 1074 had the best response to an exemplary nano-colloid suspension of poly(PLKGA) at MIC and MBC of 125 pg / ml. Table 1 below shows the MIC results of exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure. Table 2 below shows MBC results for exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosure.Table 1: MIC results of exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosureRef- 1403-02-8765Table 2: MBC results of exemplary nano-colloid suspension of polyphenyllactide and an exemplary nano-colloid suspension of poly(PLKGA), consistent with one or more exemplary embodiments of the present disclosureExample 2: SN-38 fluorescence and concentration equation[000105] Considering the high sensitivity and accuracy of measuring 7-Ethyl-10- hydroxycamptothecin (SN-38) fluorescence intensity, wavelengths of 377 and 557 nm were chosen for the excitation and emission of SN-38 fluorescence, respectively. Owing to the intense SN-38 fluorescence, the microplate reader's sensitivity (Biotek, USA) was adjusted to 50%. Initially, a 96-well plate was filled with three replicates of serial dilutions of SN-38 solution (40, 20, 10, 5, 2.5 and 1.25 pg / 100 pl Dimethylsulfoxide (DMSO)), and the intensity of the fluorescence was evaluated. Excel was then used to compute the concentration equation, logarithmic correlation, and relation curve in order to estimate the amount of SN- 38 that will be used in subsequent trials. Serial dilutions of poly(PLKGA) in DMSO (10, 5, 2.5, 1.25, 0.625 mg / 100 pl) separately and in combination with SN-38 (2 pg) were prepared for fluorescence measurement to ensure that poly(PLKGA) did not interfere with the SN-38 fluorescence. FIG. 7 illustrates the standard curve 700 of fluorescence intensity of the free form of SN-38 (mean ± SD, N = 3), consistent with one or more exemplary embodiments ofRef- 1403-02-8765 the present disclosure. As shown in FIG. 7, poly(PLKGA) emitted no fluorescence at all, and the fluorescence intensity of SN-38 (2 pg) was unaffected by any poly(PLKGA) concentration. For additional trials, the SN-38 concentration equation with a correlation coefficient (R2) = 0.98 was employed.Example 3: Preparation and optimization of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38[000106] First, a stock solution of 10 mg / ml SN-38 in DMSO was prepared and serial amounts were added to 10 pl of poly(PLKGA) in DMSO (100 mg / ml stock solution). Then, the volume of DMSO comprising poly(PLKGA) and SN-38 was increased to 20 pl, and 80 pl of ethanol was added and vortexed. Then slowly addition of distilled water (900 pl) to the organic phase formed a white colloid. Then 500 pl of 10% sorbitol and 500 pl of 2% polyvinyl alcohol (PVA, 30-70 kDa) in distilled water were added and mixed. A white colloid was generated after adding organic solution of poly(PLKGA) and SN-38 (100 pl) gradually to 900 pl of distilled water. Then the nano-colloid was added to 1000 pl of 5% sorbitol and 1% polyvinyl alcohol (PVA, 30-70 kDa) in distilled water. After that the nanocolloid was centrifuged for 10 minutes at 10000 rpm, and the supernatant, which included water, organic solvents, and free SN-38 was discarded, so 1 ml of distilled water was added to the precipitate and stirred until completely suspended. Then the nano-colloid was transferred to a new microtube, so the free SN-38 was separated from the final formulation in the process of centrifugation and resuspension. In order to determine the amount of loaded SN-38, the colloid was centrifuged once more for ten minutes at 10,000 rpm. The precipitate was then dried for thirty minutes at 60°C, dissolved in 100 pl of DMSO, and placed into a 96-well plate. Ultimately, a graph representing the loading content percentage (LC% = loaded drug to polymer w / w%) and encapsulation efficiency (EE% = loaded drug to initial drug w / w%) was created by averaging the results from three duplicates of the fluorescenceRef- 1403-02-8765 intensity measurement. The final colloid, which contained sorbitol and PVA, was examined using Dynamic light scattering (DLS), AFM (atomic force microscopy), JPK NanoWizard II, Germany), and scanning electron microscope (SEM) experiments in order to look into the characteristics of poly(PLKGA) bound SN-38 nanoparticles.[000107] FIG. 8A illustrates the loading content 800 of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 by increasing the initial amount of SN-38 (mean ± SD, N = 3), consistent with one or more exemplary embodiments of the present disclosure. FIG. 8B illustrates the encapsulation efficiency 802 of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 nanoparticles by increasing the initial amount of SN-38 (mean ± SD, N = 3), consistent with one or more exemplary embodiments of the present disclosure. FIG. 8C illustrates AFM images 804 of poly(PLKGA) bound SN-38 nanoparticles, consistent with one or more exemplary embodiments of the present disclosure. FIG. 8D illustrates SEM images 806 of poly(PLKGA) bound SN-38 nanoparticles, consistent with one or more exemplary embodiments of the present disclosure. FIG. 8E illustrates the SEM image 808 of an exemplary nano-colloid suspension of poly(PLKGA) (1 mg / ml), consistent with one or more exemplary embodiments of the present disclosure.[000108] As shown in FIG. 8A, the LC% graph indicates that drug loading has grown with an increase in the initial concentration of SN-38 during formulation and eventually the loading slope tends to zero. As shown in FIG. 8B, the percentage of loaded SN-38 to initial SN-38, increases at the beginning and decreases at the end of EE% curve and reaches the maximum value at inflection point around 80 pg. Therefore, the 8% ratio (initial SN-38 to poly(PLKGA) w / w%) with LC = 1% and EE = 12.5% was selected as the optimal condition for preparation of poly(PLKGA) bound SN-38 nanoparticles.[000109] Before adding sorbitol and PVA solutions, the properties of exemplary nanocolloid suspension of poly(PLKGA) and exemplary nano-colloid suspension ofRef- 1403-02-8765 poly(PLKGA) bound SN-38 were examined using DLS. While the average diameter of poly(PLKGA) bound SN-38 nanoparticles was 201 nm with PDI = 0.04 and zeta potential = -26.5 mV, the average diameter of poly(PLKGA) nanoparticles was 135 nm with PDI = 0.08 and zeta potential = - 17.5 mV. This suggests that following SN-38 loading, the particle diameter increased and the zeta potential decreased. After adding sorbitol and PVA solution, centrifugation and resuspension of the precipitate in distilled water, the properties of poly(PLKGA) bound SN-38 nanoparticles were evaluated using AFM, SEM, and DLS assays. The nano-colloid particles had an average diameter of 197 ± 5 nm, a zeta potential of 3.4 ± 1 mV, and a PDI of 0.17 ± 0.03. As a result, following PVA coating, the diameter of particles remained unchanged, but the homogeneity was reduced and the zeta potential changed from negative to positive. As shown in FIGs. 8B and 8C, AFM and SEM photos verified the poly(PLKGA) bound SN-38 nanoparticles diameter in the 200 nm range with good homogeneity similar to the DLS test. PVA coating caused the particles to become more spherical, less lipophilic, and spaced apart from one another. Additionally, enhancing nanoparticles hydrophilicity lengthens blood circulation and increases the effectiveness of medication by preventing the reticuloendothelial system Phagocytosis.Example 4: Evaluation of the stability and release of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38[000110] First, 10 pg of an exemplary poly(PLKGA) bound SN-38 nanoparticles in 1 ml phosphate buffer saline (pH = 7.4) and 10 pg of an exemplary poly(PLKGA) bound SN-38 nanoparticles in 1 ml citrate buffer (pH = 5.5), were added to microtubes (in three duplicates). Then the tubes were covered, closed, and shaken in a shaker incubator at 37 °C and 100 rpm. Then after 1, 3, 6, 12, 24, 48, 72, 96, 120, 144, 168, 192, 216, and 240 hours, an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 was moved to fresh microtube and shaken in an identical manner. Then the drained microtubes were dried at 40 °C, and keptRef- 1403-02-8765 aside. On the tenth and fifth days, an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 was seen unstable in the phosphate buffer and citrate buffer respectively. So an exemplary nano-colloid suspension was centrifuged at 10,000 rpm for ten minutes and the supernatant was then discarded, and the microtube including the sediment was dried at 40 °C. Subsequently, all the microtubes were vortexed with 100 pl of DMSO and the fluorescence intensity of DMSO solutions were detected by the microplate reader for calculating the SN- 38 release profile. FIG. 9 illustrates a graph 900 for presenting cumulative release of SN-38 from an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in phosphate and citrate buffers over time (mean ± SD, N = 3, t = 37 °C), consistent with one or more exemplary embodiments of the present disclosure.[000111] The fluorescence emission of released SN-38 from an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 was detected with high sensitivity. By the fifth day, almost 50% of SN-38 had been released gradually at a constant rate in phosphate buffered saline. Between the 5th and 6th days, an acceleration in the release of SN-38 was observed, and then until the ninth day, it was released at the prior rate. An unstable pale white colloid containing precipitate was noticed on the tenth day. Colloid precipitation, actually, denotes a partial hydrolysis of the polymer structure and the breakdown of colloid such that water penetrates the interior layers, increasing the density and settling of an exemplary nanocolloid suspension of poly(PLKGA) bound SN-38. Although an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 was not completely degraded by the 10th day, 90% of SN-38 was released from an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38. Within the first twenty-four hours, 50% of SN-38 was released from an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in citrate buffer at a rapid pace, followed by a decrease in rate during the next three days, Thus, by the fourth day, 80% had been released. On the 5th day, breakdown was observed. So, an exemplary nano-colloidRef- 1403-02-8765 suspension of poly(PLKGA) bound SN-38 was centrifuged and the precipitate was dried after removing the supernatant and dissolved in DMSO for the residual amount of SN-38 detection. Totally, 90% of SN-38 was released by the 5th day, which was half the release time in phosphate buffer.[000112] The release profile of SN-38 was faster in acidic pH, where the majority released by the fifth day, while 50% of SN-38 released under neutral condition by the fifth day. In citrate buffer, there was a 50% burst release in the first 24 hours, followed by a reduced and steady rate until the fifth day, while in phosphate buffer, the release rate was gradual. The presence of two layers in an exemplary poly(PLKGA) bound SN-38 nanoparticle is shown by a shift in release rate in both buffers at the 50% point. Long, heavy chain polymers create the inner layer of the nanoparticle during formation, whereas short, light chain polymers cover the inner layer to form the outer layer. In this manner, about half of the SN-38 is loaded into the outer layer and the other half into the inner layer. The inner layer greater weight and density make it more resistant to hydrolysis, which lengthens the releasing time. The profile indicates that the release of SN-38 is directly related to acidity and time. Consequently, the lysosome and tumor acidic environments promote the breakdown of an exemplary nanocolloid suspension of poly(PLKGA) bound SN-38.Example 5: Evaluation of the cytotoxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38[000113] Cell lines from C26 (mouse colon cancer), HCT116 (human colon cancer), and CHO (Chinese hamster ovary) were subjected to the viability test (MTT assay). Following three logarithmic growth conditions passages, the cells were trypsinized and 5000 cells were planted in 96-well plates with 100 pl of full culture media (RPMI 1640 + 10% FBS). After 24 hours, the C26 and CHO cell lines stuck and formed on the flask bottom, followed by the HCT116 cell line after 48 hours. Consequently, the plate was split into four groups and theRef- 1403-02-8765 medium was replaced with 100 pl of new medium. First, 100 pl of free SN-38 in sodium chloride (final concentrations of 10, 5, 2.5, 1.25, 0.625, and 0.312 pg / ml including 2% DMSO) was given to the positive control group. The second group was administered 100 pl nano-colloid suspension of poly(PLKGA) bound SN-38 in sodium chloride equally as the SN-38 dose of the first group. The third group received 100 pl of an exemplary nano-colloid suspension of poly(PLKGA) in sodium chloride equally as the polymer dose of second group, and the fourth, negative control group received 100 pl of sodium chloride (0.9%) with a final concentration of 2% DMSO. The test was done in four replicates. At this stage, the plate was incubated for three hours at 37 °C with 5% carbon dioxide (treatment duration = three hours). Subsequently, 100 pl of fresh medium was replaced to each well, and after a 24-hour incubation period, 10 pl of MTT (tetrazolium yellow dye) in phosphate buffered saline (5 mg / ml) was added. The wells were then incubated for three hours, and the live cells reduced the yellow MTT to an insoluble purple formazan, which serves as a cellular viability indicator. After the medium was removed, the plate was dried at 40°C to dissolve the formazan dye. Next, each well received 100 pl of DMSO, which was applied and agitated for a quarter at room temperature to thoroughly dissolve the formazan's purple hue in the DMSO. Ultimately, a microplate reader was used to quantify the formazan solution's absorbance at 570 and 630 nm, and a viability% graph was created. Using Prism software, the IC50 and statistical significance (p-value < 0.05) were determined.[000114] FIG. 10A illustrates graph 1000 for presenting C26 cell line viability test after 3- hour treatment of free SN-38, poly(PLKGA) and poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10B illustrates IC50 calculation 1002 of free SN-38 in C26 cell line after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10C illustrates IC50 calculation 1004 of an exemplary nano-Ref- 1403-02-8765 colloid suspension of poly(PLKGA) bound SN-38in C26 cell line after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10D illustrates statistical comparison 1006 of the viability of C26 cell line after 3-hour treatment of .25 pg / ml free SN-38 and 1.25 pg / ml poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10E illustrates graph 1008 of HCT116 cell line viability test after 3 hours Treatment of free SN-38, poly(PLKGA) and poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10F illustrates IC50 calculation 1010 of free SN-38in HCT116 cell line after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10G illustrates IC50 calculation 1012 of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in HCT116 cell line after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10H illustrates statistical comparison 1014 of the viability of HCT116 cell line after 3-hour treatment of 2.5 pg / ml free SN-38 and 2.5 pg / ml poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 101 illustrates the graph 1016 of CHO cell line viability test after 3-hour treatment of free SN-38, poly(PLKGA) and poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10J illustrates statistical comparison 1018 of the viability of CHO cell line after 3-hour treatment of 5 pg / ml free SN-38 and 5 pg / ml poly(PLKGA) bound SN-38 (mean ± SD, N = 4), consistent with one or more exemplary embodiments of the present disclosure. FIG. 10K illustrates IC50 calculation 1020 of an exemplary nano-colloid suspension of poly(PLKGA) on cell lines after 3 hours of treatment by Prism software (mean, N = 4), consistent with one or more exemplary embodiments ofRef- 1403-02-8765 the present disclosure. The C26 mouse colon cancer cell line's viability graph shows that SN- 38 cytotoxicity is dose-dependent. However, an exemplary nano-colloid suspension of poly(PLKGA) also exhibits cytotoxicity that is dependent on dose, as seen at a dose of > 125 pg / ml (corresponding to 1.25 pg / ml of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38). So with a fall in viability down to 60%, the exemplary nanocolloid suspension of poly(PLKGA) bound SN-38 graph shows the synergism of SN-38 and the exemplary nano-colloid suspension of poly(PLKGA)cytotoxicity even at the lowest concentration (0.312 pg / ml). The graph indicates that the IC50 of free SN-38 is around 8 pg / ml, and Prism software confirms this value. Meanwhile, Prism yielded an IC50 of 1.6 pg / ml for an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38. Consequently, the IC50 was lowered to one-fifth due to the synergistic toxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38. Prism software was used to assess the viability of C26 at 1.25 pg / ml equivalent concentration of treatments in order to compare the cytotoxicity of free SN-38, an exemplary nano-colloid suspension of poly(PLKGA), and an exemplary nano-colloid suspension of Poly(PLKGA) bound SN-38. The results showed that the cytotoxicity of an exemplary nano-colloid suspension of Poly(PLKGA) bound SN-38 was significantly higher than that of saline, free SN-38, and an exemplary nano-colloid suspension of poly(PLKGA) (p < 0.0001). The HCT116 human colorectal cancer cell line's viability diagram shows that it is resistant to free SN-38, even at the maximum concentration (10 pg / ml), with 68% vitality. On the other hand, an exemplary nano-colloid suspension of poly(PLKGA) exhibits dose dependent toxicity, which increased upon SN-38 loading. Using prism, the IC50 of an exemplary nano-colloid suspension of poly(PLKGA) was determined to be 984 pg / ml. Furthermore, it was found that the IC50 of the free SN-38 and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 were, respectively, 72 pg / ml and 3.4 pg / ml. Reducing the IC50 to one twentieth by synergisticRef- 1403-02-8765 toxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 indicated HCT116 cell line was sensitized to SN-38. When comparing the viability of HCT116 at 2.5 pg / ml equivalent concentration of treatments using Prism, cytotoxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 is significantly (p < 0.0001) higher than that of saline, free SN-38, and an exemplary nano-colloid suspension of poly(PLKGA). So, the exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 has hindered the HCT116 resistance. The CHO cell line's viability graph shows low SN-38 toxicity even at the highest dose (10 pg / ml) since, 90% of the cell line is still viable. But, the toxicity of an exemplary nano-colloid suspension of poly(PLKGA) and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 were dose-dependent. While an exemplary nanocolloid suspension of poly(PLKGA) bound SN-38 is more cytotoxic than an exemplary nanocolloid suspension comprising poly(PLKGA), the difference is not as great as it is for C26 and HCT116, which are impacted by SN-38 low toxicity on CHO. Consequently, at 5 pg / ml equal dose of an exemplary nano-colloid suspension of poly(PLKGA) and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38, there is no statistically significant difference in CHO viability. An exemplary nano-colloid suspension of poly(PLKGA) exhibits dose-dependent toxicity in the three cell lines — C26, HCT116, and CHO — with IC50 values of 264, 984, and 688 pg / ml, respectively, according to the viability assays. The viability tests revealed that SN-38 exhibited limited dose dependent toxicity on the human colon cancer cell line (HCT116) due to drug resistance and dose dependent toxicity on the mouse colon cancer cell line (C26). However, it did not exhibit dose dependent toxicity on the normal hamster ovary cell line (CHO). On three cell lines, an exemplary nano-colloid suspension of poly(PLKGA) exhibited dose-dependent toxicity at concentrations more than 125 pg / ml. The half-life concentration (IC50) of an exemplary nano-colloid suspension of poly(PLKGA) on HCT116 was nearly four times higher than that of C26 (984 pg / ml againstRef- 1403-02-8765264 pg / ml, respectively). This indicates biological rather than chemical toxicity, and the mechanism of action is anticipated to be linked to increased cell proliferation because of the toxicity on CHO (688 pg / ml), as a normal cell. The synergistic activity is confirmed by the toxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 on C26 and HCT116 cell lines at IC50 concentration, which differed significantly from the toxicity of free SN-38 and an exemplary nano-colloid suspension of poly(PLKGA) separately. Due to the lack of SN-38 toxicity, the toxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 on CHO, was not significantly different from an exemplary nano-colloid suspension of poly(PLKGA) toxicity at IC50. However an exemplary nanocolloid suspension of poly(PLKGA) showed significant toxicity. This affirms the favorable release profile of SN-38 from the poly(PLKGA) bound SN-38 nanoparticles over 24-hour cell incubation after 3-hour exposure, because SN-38 is responsible for the significant difference in toxicity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN- 38 and an exemplary nano-colloid suspension of poly(PLKGA) on C26 and HCT116.Example 6: Evaluation of cellular uptake of poly(PLKGA) bound SN-38 nanoparticles by flowcytometry[000115] First, two hundred thousand cells (C26 and HCT116 separately) in 500 pl of complete culture medium were seeded in three wells of a 24-well plate and incubated at 37 °C (5% CO2) for 24 and 48 hours, respectively. Then, the medium was changed with 250 pl of fresh medium. The first group received 250 pl of free SN-38 in saline solution (final concentration of 10 pg / ml and 2% DMSO) and the second group received 250 pl of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 in saline solution equally as the SN-38 dose of first group and the third group, received 250 pl of saline solution (0.9%) with a final concentration of 2% DMSO and the plate was placed in incubator (1.5 hour). Then, the medium of plate was discarded and washed three times with phosphate bufferedRef- 1403-02-8765 saline, and 100 pl of trypsin was added to each well, incubated for a few minutes, neutralized by complete medium, and the cells were isolated by pipetting. Then the cell suspension was centrifuged and the cell pellet resuspended in 1 ml of phosphate buffered saline after removing the supernatant. Finally, the SN-38 fluorescence intensity was measured by flow cytometer. Flow cytometry histogram analysis in both C26 and HCT116 cell lines after treatment (1.5 h) indicate an increase in the fluorescence intensity of SN-38 group compared to the saline group (negative control) and also an increase in the fluorescence intensity of poly(PLKGA) bound SN-38 group compared to the SN-38 group. FIG. 11A illustrates flow cytometry histogram 1100 of C26 cell line after 90 minutes of treatment with 10 pg / ml free SN-38 and 10 pg / ml poly(PLKGA) bound SN-38, consistent with one or more exemplary embodiments of the present disclosure. FIG. 11B illustrates flow cytometry histogram 1102 of HCT116 cell line after 90 minutes of treatment with 10 pg / ml free SN-38 and 10 pg / ml poly(PLKGA) bound SN-38, consistent with one or more exemplary embodiments of the present disclosure. The optimum cellular uptake of Poly(PLKGA) bound SN-38 is confirmed by the flow cytometry test, which showed a 10 and 100 fold increase in C26 and HCT116 fluorescence intensity, respectively, by poly(PLKGA) bound SN-38 treatment compared to the free SN-38. These results align with the viability test findings.Example 7: Evaluation of cellular uptake of poly(PLKGA) bound SN-38 nanoparticles by fluorescence imaging[000116] Initially, three wells of a 24-well plate were seeded with 50,000 cells in 0.5 ml of complete culture media for each cell line (C26 and HCT116 separately). The cells were then incubated at 37°C with 5% CO2 until they attained optimal growth and adhesion after 24 and 48 hours, respectively. Next, 250 pl of fresh medium was changed with the original medium. The first group, received 250 pl of free SN-38 in saline solution (final concentration of 10 pg / ml and 2% DMSO) and the second group received 250 pl of an exemplary nano-colloidRef- 1403-02-8765 suspension of poly(PLKGA) bound SN-38 in saline solution equally as the SN-38 dose of the first group and the third group, received 250 pl of saline solution (0.9%) with a final concentration of 2% DMSO and the plate was placed in incubator for 1.5 hour. Following the removal of each well medium and three phosphate buffered saline washes, 250 pl of the complete culture medium was added. An Olympus 1X53 inverted microscope (Japan) was used to record optical and fluorescent pictures, which were then merged using AutoCAD software. In this test, HCT116 cells were imaged optically and fluoroscopically after 24-hour treatment as well, without being washed after medium removal.[000117] FIG. 12 illustrates the image 1200 of optical microscope (A), fluorescence microscope (B) and integrated (C) images of C26 cell line after 90-minute treatment of 10 pg / ml free SN-38 (1202) and 10 pg / ml poly(PLKGA) bound SN-38 (1204). FIG. 13 illustrates the image 1300 of optical microscope (A), fluorescence microscope (B) and integrated (C) images of HCT116 cell line after 90-minute treatment of 10 pg / ml free SN-38 (1302) and 10 pg / ml poly(PLKGA) bound SN-38 (1304). FIG. 14 illustrates the image 1400 of optical microscope image of HCT116 cell line after 24-hour treatment of 10 pg / ml free SN-38 (A) and fluorescence emission of the same image (B). FIG. 15 illustrates the image 1500 of optical microscope image 1500 of HCT116 cell line after 24-hour treatment of 10 pg / ml poly(PLKGA) bound SN-38 (A) and fluorescence emission of the same image (B). The fluorescence images of C26 and HCT116 cell lines after one and half hour treatment show an increase in the fluorescence intensity of poly(PLKGA) bound SN-38 group compared to the free SN-38 group, while no emission was detected in the negative control group (sodium chloride 0.9%). The attachment of poly(PLKGA) bound SN-38 to the surface of cells and morphological alterations such as rounded shape and cell detachment observed in both cell lines, shows an increased cytotoxicity in compared to the free SN-38 treated cells with normal morphology. After 24 hours of treatment, the HCT116 cell optical andRef- 1403-02-8765 fluorescence images clearly demonstrated the cytotoxicity of the poly(PLKGA) bound SN- 38 in comparison to the free SN-38. The low soluble SN-38 sedimentation, which is in balance with the soluble portion, is confirmed by the SN-38 crystal in the free SN-38 medium. HCT116 cells remain entirely normal and alive (transparent) despite SN-38 saturation of the media. This is because of resistance. The good poly(PLKGA) bound SN-38 absorption and release was shown by the appearance of dark, dead (apoptotic) cells surrounded by bright nanoparticles and green light halos in the 24-hour treatment image of the poly(PLKGA) bound SN-38. Consequently, the HCT116 resistance has been overcome by the synergistic toxicity of poly(PLKGA) bound SN-38.Example 8: Evaluation the anti-tumor activity of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38[000118] In this regard, 24 female BALB / c mice weighing 20 g and around 5 week old were acquired from the Iranian Pasteur Institute. After shaving of the right flank, mice were given a subcutaneous injection of 100 pl of C26 suspension containing 3 x 105cells in phosphate buffered saline, following an intraperitoneal injection of 150 pl of ketamine - xylazine anesthetic solution. On the eleventh day following injection, all mice showed signs of tumor growth, which were categorized into three groups based on the size of the tumor: small, medium, and big (15-140 mm3). After that, the mice were divided equally into four groups, with two mice having little tumor, three having medium tumor, and one having big tumor in each group. The groups were then given name randomly. The first group, known as the positive control, was given three separate doses of 80 pg (4 mg / kg) SN-38, totally 240 pg free SN-38 (12 mg / kg). The second group was administered an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 equally as the SN-38 dose of first group. The third group received an exemplary nano-colloid suspension of poly(PLKGA) equally as the polymer dose of second group, so each mouse received 24 mg (1.2 g / kg) of poly(PLKGA) inRef- 1403-02-8765 three seperate doses (8 mg or 400 mg / kg of poly(PLKGA) per dose). Three doses of sodium chloride 0.9% were given to the last group, which was the negative control. As a result, three injections were given to each mouse through the tail vein on days 11, 14, and 17 following the Tumor cell inoculation. To make the formulation of free SN-38, the SN-38 solution in DMSO (80 pg / 8 pl) was added to 40 pl of glycophorol solvent followed by mixing with distilled water upto volume of 200 pl. Sterile distilled water was used to prepare an exemplary nano-colloid suspension of poly(PLKGA) and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38. Over the course of 33 days of research, the weight and size of tumors in the mice were measured using a laboratory scale (AND, Japan) and digital calipers (Asimeto, Germany). The calculation of tumor volume involved multiplying the small and large diameters by half of the height. The mice were anesthetized and euthanized at the conclusion of investigation.[000119] Grouping, weighing, tumor volume measurement, and the first injection were completed on the eleventh day following tumor induction in BALB / c mice. This day was designated as the first day and the starting point for data recording. There were no signs of unhealthy after saline, an exemplary nano-colloid suspension of poly(PLKGA) and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 injections and the mice had completely normal, dynamic and stable manifestation However, the free SN-38 injected mice showed tachycardia and tachypnea and immobility, which recovered after 20 minutes. One mouse was chosen on day 33 from each of the following groups: an exemplary nanocolloid suspension of poly(PLKGA), an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38, positive control (free SN-38), and negative control (saline). After anesthetic and euthanasia induction, the primary organs of the mice, including the heart, lung, kidneys, spleen, liver, and tumor, were dismembered, cleaned in phosphate-buffered saline, fixed in 10% formalin, followed by embedding in paraffin, cutting into 5 pm pieces,Ref- 1403-02-8765 staining with hematoxylin-eosin and observing by Olympus BX51 microscope for a histological study.[000120] FIG. 16A illustrates average tumor volume 1600 of mice during 22 days (mean ± SD, N = 6, injection days 1, 4 and 7), consistent with one or more exemplary embodiments of the present disclosure. FIG. 16B illustrates statistical analysis of the difference in final average tumor volume 1602 of mice (mean ± SD, N = 6), consistent with one or more exemplary embodiments of the present disclosure. FIG. 16C illustrates average weight of mice during the test of anti-tumor activity (mean ± SD, N = 6) 1604, consistent with one or more exemplary embodiments of the present disclosure. FIG. 16D illustrates statistical analysis 1606 of the difference in final average weight of mice during the test of anti-tumor activity (mean ± SD, N = 6), consistent with one or more exemplary embodiments of the present disclosure.[000121] Over the course of 22-day trial, the tumor growth of poly(PLKGA) bound SN-38 group was nearly identical to that of the free SN-38 group, while the tumor volume of the saline and poly(PLKGA) groups increased at the same pace. Compared to the free SN-38 and poly(PLKGA) bound SN-38 groups, there is a clear rise in tumor volume of the control and poly(PLKGA) groups. After the first injection, the tumor growth in one of the mice treated with poly(PLKGA) bound SN-38, which had a tiny initial volume (15 mm3), showed a decreasing trend and vanished a day later after the third injection. In another mouse with a big primary tumor volume (91 mm3) that was nearly constant for the first week and three injections, the tumor size gradually shrinked during the second week and vanished on the seventeenth day. In the two mice, the cancer remission did not recur even two weeks after the trial ended. During the trial, the tumor growth in the other poly(PLKGA) bound SN-38 treated mice was the same as free SN-38 treated mice. Consequently, compared to the free SN-38 group, the average tumor volume was less in the group of poly(PLKGA) bound SN-Ref- 1403-02-876538. The value of the standard deviation gradually rises in all groups because the mice with small, medium, and big primary tumors were distributed equally among all groups and the difference in the volume of small and large tumors increased over the course of the study. Also, the standard deviation value of poly(PLKGA) bound SN-38 group is higher than others due to the two tumors treatment. The non-parametric Kruskal-Wallis test was examined in the statistical analysis of the variation in tumor volume across the groups on the final day because of the small sample size and high variance. The difference in tumor size of poly(PLKGA) bound SN-38 treated group was considered significant with p- value < 0.05 according to the robustness of Kruskal -Wallis test. However, by normality assumption and the One-way ANOVA test, the difference in tumor size is highly significant with p-value < 0.001. Compared to in vitro studies, an exemplary nano-colloid suspension of poly(PLKGA) did not exhibit tumor toxicity; this could be due to the lack of appropriate concentration of nano-colloid in the tumor microenvironment. On the last day of research, the anti-tumor activity of free SN-38 was not statistically significant, despite the considerable drop in tumor volume. However, the tumor toxicity of poly(PLKGA) bound SN-38 was significant with a 58% decrease in tumor volume (p < 0.05). According to the lack of anti-tumor activity by poly(PLKGA), the higher toxicity of poly(PLKGA) bound SN-38 in comparison to the free SN-38 is due to the targeted and favorable drug delivery, not synergistic effect. Furthermore, the steady reduction in tumor size and remission observed in the two of six mice, suggests the continuous drug delivery of poly(PLKGA) bound SN-38.[000122] Weight measurements taken during the investigation on mice revealed that the weight of poly(PLKGA) bound SN-38, poly(PLKGA) and saline groups increased somewhat, but the weight of free SN-38 group didn’t change. Despite the fact that the Free SN-38 group weight average was lower than that of the other three groups, a statistical comparison of groups weight on the final day revealed no significant difference. While theRef- 1403-02-8765 free SN-38 injection caused immobility, tachycardia, and tachypnea in the mice, the normal behaviour of mice following the injection of an exemplary nano-colloid suspension of poly(PLKGA) and poly(PLKGA) bound SN-38 and weight gain, indicate the safety of an exemplary nano-colloid suspension of poly(PLKGA) and targeted drug delivery of poly(PLKGA) bound SN-38. Furthermore, the fact that 36 injections of an exemplary nanocolloid suspension of poly(PLKGA) and poly(PLKGA) bound SN-38 were completed successfully and without any apparent complications suggests that the product is safe and has favourable physicochemical characteristics.[000123] FIG. 17A illustrates optical microscope images 1700 of the mouse liver tissue at the end of anti-tumor activity test, after three injections of free SN-38 and an exemplary nanocolloid suspension of poly(PLKGA) bound SN-38 (total 240 pg (12 mg / kg)) (the dose of poly(PLKGA) was equal to the polymer in poly(PLKGA) bound SN-38), consistent with one or more exemplary embodiments of the present disclosure. FIG. 17B illustrates optical microscope images (10X magnification) 1702 of the mouse organ tissue anti-tumor activity test, after three injections of free SN-38 and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 (total 240 pg (12 mg / kg)) (the dose of poly(PLKGA) was equal to the polymer in poly(PLKGA) bound SN-38), consistent with one or more exemplary embodiments of the present disclosure. FIG. 17C illustrates optical microscope images (10X magnification) 1704 of the mouse tumor tissue at the end of anti-tumor activity test, after three injections of free SN-38 and an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38 (total 240 pg (12 mg / kg)) (the dose of poly(PLKGA) was equal to the polymer in poly(PLKGA) bound SN-38), consistent with one or more exemplary embodiments of the present disclosure.[000124] The grey color of liver in mouse whom received free SN-38 was the only difference detected during the dissection, while other mice had brown color liver. TheRef- 1403-02-8765 histological analysis showed that all groups heart, lungs, spleen, and kidneys were healthy. Inflammation, lymphocytes accumulation and hepatitis were seen in the liver tissue of free SN-38 treated mouse, while no liver damage observed in the poly(PLKGA) and Poly(PLKGA) bound SN-38 treated mice. The tumor tissue had a compact structure and cancer cells with large and clear nucleus which shows tumor growing in saline and poly(PLKGA) treated mice, while extensive and widespread necrosis was observed in tumor tissue of the free SN-38 and Poly(PLKGA) bound SN-38 treated mice. Therefore, the poly(PLKGA) bound SN-38 nano-particles had favourable SN-38 delivery to the tumor without liver damage.Example 9: Evaluation the tissue distribution of an exemplary nano-colloid suspension of poly(PLKGA) bound SN-38[000125] Initially, three female BALB / c mice weighing 20 g and approximately 5 weeks old had their right flanks shaved. The right flank was then subcutaneously injected with 100 pl of C26 suspension including 3 x 105cells in phosphate buffered saline (pH = 7.4), following intraperitoneally injection of 150 pl ketamine-xylazine anesthesia solution. The size of tumors was around 300 mm3after two weeks. The first was subsequently injected with 200 pl of 0.9% sodium chloride, and the second and third mice were injected with 200 pl of poly(PLKGA) bound SN-38 an exemplary nano-colloid of poly(PLKGA) bound SN- 38 (80 pg, 4 mg / kg) through tail vein. The first and second mice were anesthetized and euthanized 6 hours and the third mouse 24 hours post injection. Then the primary organs including heart, lungs, kidneys, spleen, liver and tumor were dismembered and twice-washed in phosphate buffered saline and dried in a sterile gauze. Lastly, the Kodak Multispectral Imaging System (470 nm excitation - 550 nm emission) was used to assess the organs fluorescence intensity for the distribution of poly(PLKGA) bound SN-38.Ref- 1403-02-8765[000126] All three mice organs were healthy and comparable during the dissection process, and no unusual cases were found. Six hours after injection, there was no difference in the primary organ fluorescence intensity between the mice treated with saline and poly(PLKGA) bound SN-38. The fluorescence of heart, lungs and spleen in mouse 24 hours after injection of the exemplary nano-colloid of poly(PLKGA) bound SN-38 was similar to the saline treated mouse, while the kidneys, liver and tumor indicated higher intensity than the control. The spleen functions as a phagocyte system and blood filter for foreign particles, much like a big lymph gland. Therefore, the absence of poly(PLKGA) bound SN-38 in the spleen indicates a lack of immunological sensitization. Consequently, a targeted drug delivery system is confirmed by poly(PLKGA) bound SN-38 predominant distribution in the tumor and its absence in organs like the lungs, heart, and spleen. Poly(PLKGA) bound SN-38 entrapment in the liver as the most significant detoxification organ with high blood supply is natural. However, the lack of liver damage shows liver as a reservoir for temporary accumulation of poly(PLKGA) bound SN-38 and further circulation to target tumor, which is approved by the similar fluorescence intensity of tumor and liver and indicates the high penetration of poly(PLKGA) bound SN-38 into the tumor tissue with restricted blood supply. The kidneys low fluorescence 24 hours after injection, shows the poly(PLKGA) bound SN- 38 is stable in blood with a favorable 24-hour circulation time and low degradation. FIG. 18 illustrates fluorescence images 1800 of the mouse organs, 6 hours and 24 hours after intravenous injection of an exemplary nano-colloid suspension of poly(PLKGA) bound SN- 38 in comparison to intravenous injection of sodium chloride 0.9%, consistent with one or more exemplary embodiments of the present disclosure.[000127] While the foregoing has described what are considered to be the best mode and / or other examples, it is understood that various modifications may be made therein and that the subject matter disclosed herein may be implemented in various forms and examples, and thatRef- 1403-02-8765 the teachings may be applied in numerous applications, only some of which have been described herein. It is intended by the following claims to claim any and all applications, modifications and variations that fall within the true scope of the present teachings.[000128] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, including in the claims that follow, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.[000129] The scope of protection is limited solely by the claims that now follow. That scope is intended and should be interpreted to be as broad as is consistent with the ordinary meaning of the language that is used in the claims when interpreted in light of this specification and the prosecution history that follows and to encompass all structural and functional equivalents. Notwithstanding, none of the claims are intended to embrace subject matter that fails to satisfy the requirement of Sections 101, 102, or 103 of the Patent Act, nor should they be interpreted in such a way. Any unintended embracement of such subject matter is hereby disclaimed.[000130] Except as stated immediately above, nothing that has been stated or illustrated is intended or should be interpreted to cause a dedication of any component, step, feature, object, benefit, advantage, or equivalent to the public, regardless of whether it is or is not recited in the claims.[000131] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study except where specific meanings have otherwise been set forth herein. Relational terms such as first and second and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying anyRef- 1403-02-8765 actual such relationship or order between such entities or actions. An element proceeded by “a” or “an” does not, without further constraints, preclude the existence of additional identical elements in the process, method, article, or apparatus that comprises the element.[000132] Unless otherwise stated, all measurements, values, ratings, positions, magnitudes, sizes, and other specifications that are set forth in this specification, are approximate, not exact. They are intended to have a reasonable range that is consistent with the functions to which they relate and with what is customary in the art to which they pertain.[000133] It will be understood that the terms and expressions used herein have the ordinary meaning as is accorded to such terms and expressions with respect to their corresponding respective areas of inquiry and study, except where specific meanings have otherwise been set forth herein. Relational terms such as “first” and “second” and the like may be used solely to distinguish one entity or action from another without necessarily requiring or implying any actual such relationship or order between such entities or actions.[000134] The Abstract of the Disclosure is provided to allow the reader to quickly ascertain the nature of the technical disclosure. It is submitted with the understanding that it will not be used to interpret or limit the scope or meaning of the claims. In addition, in the foregoing Detailed Description, it may be seen that various features are grouped together in various implementations. This is for purposes of streamlining the disclosure, and is not to be interpreted as reflecting an intention that the claimed implementations require more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive subject matter lies in less than all features of a single disclosed implementation. Thus, the following claims are hereby incorporated into the Detailed Description, with each claim standing on its own as a separately claimed subject matter.[000135] While various implementations have been described, the description is intended to be exemplary, rather than limiting and it will be apparent to those of ordinary skill in theRef- 1403-02-8765 art that many more implementations and implementations are possible that are within the scope of the implementations. Although many possible combinations of features are shown in the accompanying figures and discussed in this detailed description, many other combinations of the disclosed features are possible. Any feature of any implementation may be used in combination with or substituted for any other feature or element in any other implementation unless specifically restricted. Therefore, it will be understood that any of the features shown and / or discussed in the present disclosure may be implemented together in any suitable combination. Accordingly, the implementations are not to be restricted except in light of the attached claims and their equivalents. Also, various modifications and changes may be made within the scope of the attached claims.

Claims

1. Ref- 1403-02-8765What is claimed is:

1. A targeted nanocarrier for delivering drugs to targeted cells, the targeted nanocarrier comprising a nano-colloid suspension of poly(phenyllactic-co-kojic-co-gluconic acid) (poly(PLKGA)), the nano colloid suspension of poly(PLKGA) comprising: a dispersed phase comprising a plurality of nanoparticles of poly(PLKGA); and a continuous phase comprising a medium of the nano-colloid suspension of poly(PLKGA), the medium of the nano-colloid suspension of poly(PLKGA) comprising a biocompatible hydrophilic fluid.

2. The targeted nanocarrier of claim 1, wherein the targeted nanocarrier comprises a nano-colloid suspension of poly(PLKGA) with a concentration between 0.9 mg / ml and 1.1 mg / ml.

3. The targeted nanocarrier of claim 1, wherein the nanoparticles of poly(PLKGA) is coated with polyvinyl alcohol with a molecular weight between 30-70 kDa.

4. The targeted nanocarrier of claim 1, wherein the biocompatible hydrophilic fluid comprises water and sorbitol.

5. The targeted nanocarrier of claim 1, wherein the targeted nanocarrier has an anti-bacterial and anti-neoplastic activity.

6. A targeted nanocarrier for delivering drugs to targeted cells, the targeted nanocarrier comprising a nano-colloid suspension of poly(PLKGA) with a concentration between 0.9 mg / ml and 1.1 mg / ml, the nano colloid suspension of poly(PLKGA) comprising: a dispersed phase comprising a plurality of nanoparticles of poly(PLKGA) coated with polyvinyl alcohol with a molecular weight between 30-70 kDa; and a continuous phase comprising a medium of the nano-colloid suspension of poly(PLKGA), the medium of the nano-colloid suspension of poly(PLKGA) comprising a biocompatible hydrophilic fluid, the biocompatible hydrophilic fluid comprising water and sorbitol.Ref- 1403-02-87657. An anti-neoplastic and anti-bacterial composition comprising a nano-colloid suspension of poly(PLKGA) bound 7-Ethyl-10-hydroxycamptothecin (SN-38), the nano colloid suspension of poly(PLKGA) bound SN-38 comprising: a dispersed phase comprising a plurality of poly(PLKGA) bound SN-38 nanoparticles; and a continuous phase comprising a medium of the nano-colloid suspension of poly(PLKGA) bound SN-38, the medium of the nano-colloid suspension of poly(PLKGA) bound SN-38 comprising a biocompatible hydrophilic fluid.

8. The anti-neoplastic and anti-bacterial composition of claim 7, wherein the nano-colloid suspension of poly(PLKGA) bound SN-38 comprises poly(PLKGA) and SN-38 with a weight ratio of 100: 1 (poly(PLKGA): SN-38).

9. The anti-neoplastic and anti-bacterial composition of claim 7, wherein each nanoparticle of poly(PLKGA)-bound SN-38 is coated with polyvinyl alcohol with a molecular weight between 30- 70 kDa.

10. The anti-neoplastic and anti-bacterial composition of claim 7, wherein the biocompatible hydrophilic fluid comprises water and sorbitol.

11. The anti-neoplastic and anti-bacterial composition of claim 7, wherein the biocompatible hydrophilic fluid fills the space between the poly(PLKGA) bound SN-38 nanoparticles.

12. An anti-neoplastic and anti-bacterial composition comprising a nano-colloid suspension of poly(PLKGA) SN-38, the nano colloid suspension of poly(PLKGA) bound SN-38 comprising: a dispersed phase comprising a plurality of poly(PLKGA) bound SN-38 nanoparticles coated with polyvinyl alcohol with a molecular weight between 30-70 kDa; the dispersed phase comprising poly(PLKGA) and SN-38 with a weight ratio of 100: 1 (poly(PLKGA):SN-38); and a continuous phase comprising a medium of the nano-colloid suspension of poly(PLKGA) bound SN-38, the medium of the nano-colloid suspension of poly(PLKGA)Ref- 1403-02-8765 bound SN-38 comprising a biocompatible hydrophilic fluid, the biocompatible hydrophilic fluid comprising water and sorbitol, wherein the biocompatible hydrophilic fluid fills the space between the poly(PLKGA) bound SN-38 nanoparticles.

13. A method of producing polyphenyllactide with a purity ranging between 90 wt% and 95 wt%, the method comprising: forming a white solid comprising phenyllactide through an esterification reaction by adding a catalyst comprising anhydrous zinc chloride with a concentration of 1% w / w (with respect to the weight of phenyllactic acid) to phenyllactic acid while stirring in a first storage connected to nitrogen gas flow, at a temperature level between 125 °C and 135 °C, and for a time duration between 25 minutes and 35 minutes while the first storage is placed in a paraffin bath; forming a hard yellow gel comprising polyphenyllactide through ring opening polymerization reaction by adding a catalyst comprising tin(II) octoate with a concentration of 1% w / w (with respect to the weight of phenyllactide) to the white solid comprising phenyllactide in the first storage connected to nitrogen gas flow while stirring without reflux at a temperature level between 175 °C and 185 °C, and for a time duration between 55 minutes and 65 minutes; and forming a hard fragile polymeric glass comprising polyphenyllactide by cooling the hard yellow gel comprising polyphenyllactide to a temperature level between 20 °C and 25 °C, and for a time duration between 10 minutes and 15 minutes.

14. A method of producing oligo(kojic-co-gluconic acid) with a purity ranging between 90 wt% and 95 wt%, the method comprising: forming a melted mixture comprising oligo(kojic-co-gluconic acid) by mixing / stirring a freeze dried powder of kojic acid with a freeze dried powder of gluconic acid with a molar ratio of 1:1 (kojic acid: gluconic acid) on a stirrer at a temperature level between 110 °C and 130 °C, for a time duration of between 25 minutes and 35 minutes, under vacuum using aRef- 1403-02-8765 vacuum pump, and in a presence of catalysts comprising tin(II) octoate and zinc chloride with a final concentration of 1% w / w individually; forming a yellow solid comprising oligo(kojic-co-gluconic acid) by cooling the melted mixture to a temperature level of 25 °C; and forming a pure precipitate of oligo(kojic-co-gluconic acid) by washing excess amounts of kojic acid and gluconic acid from the yellow solid.

15. A method of producing poly(PLKGA) with a purity ranging between 90 wt% and 95 wt%, the method comprising: forming a first solution comprising a diphenyl ether solution of polyphenyllactide with a concentration between 240 mg / ml and 260 mg / ml by dissolving polyphenyllactide in diphenyl ether on a stirrer at a temperature level between 150 °C and 170 °C, under reflux; cooling the first solution to a predetermined temperature level of 110 °C; forming a second solution comprising a diphenyl ether solution of poly(PLKGA) by adding a powder of pure oligo(kojic-co-gluconic acid) with a concentration of 10% w / w (with respect to the weight of the powder of polyphenyllactide) to the cooled first solution while stirring on a stirrer at a temperature level between 105 °C and 115 °C and for a time duration of about 12 minutes and 18 minutes; cooling the second solution to a temperature level of 25 °C; forming a precipitate of poly(PLKGA) by adding an anti-solvent comprising ethanol solution to the cooled second solution with a predetermined volume ratio of 1: 10 (the cooled second solution: the anti- solvent); washing the precipitate of poly(PLKGA) by a solvent comprising ethanol solution with a concentration of at least 95% (v / v); and drying the washed precipitate at a temperature level of 40 °C by using an oven.

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