Castor oil based biocompatible polymer nanocarriers and their production

Abstract

The invention relates to polymer-based nanocarriers developed using castor oil and the production method of these nanocarriers.

Description

[0001] CASTOR OIL BASED BIOCOMPATIBLE POLYMER NANOCARRIERS AND THEIR PRODUCTION

[0002] Technical Field

[0003] The present invention relates to polymer-based nanocarriers developed using renewable resources (castor oil) and the production method of these nanocarriers. Said carriers may be used in targeted delivery systems to carry drug, biomolecule, bioactive molecule, and gene materials.

[0004] State of the Art

[0005] It is a difficult process to deliver the active molecules (drug molecules, proteins, enzymes, DNAs, RNAs, CRISPR / Cas9 systems) to the targeted sites in the desired quantities and without causing side effects in effectively treating diseases. There are studies in the literature on the development of bio- or polymer-based nanocarriers that effectively transport drugs, proteins, and genetic materials into cells. Commercially used carriers are usually liposomebased structures. The efficiency of targeted drug and gene delivery systems, however, needs to be improved. Therefore, unique nanocarriers are needed.

[0006] Brief Description and Objects of the Invention

[0007] With the present invention, unique nanocarriers have been developed for the transport of drug molecules (chemotherapeutic agents, antibiotics, anticancer, antioxidants, etc.), genetic materials (DNA, RNA, CRISPR / Cas9 systems, etc.), bioactive compounds (molecules obtained from plants such as quercetin, naringin, curcumin), and biomolecules (enzyme, protein, antibody, etc.) to the desired target site in the circulatory system for the effective treatment of diseases.

[0008] The synthesis method within the scope of the invention has been designed to be eco-friendly. This proposed synthesis method and the nanocarriers obtained by this method are both eco- friendly and cost effective. Description of the Figures

[0009] Figure 1. A) Particle size analysis of polymer nanocarriers, B)SEM image of polymer nanocarriers.

[0010] Detailed Description of the Invention

[0011] The nanocarriers developed within the scope of the invention were synthesized using methacrylated methyl ricinoleate obtained from castor oil and at least one water-soluble polymer reagent with an acrylate group. Preferably, the said polymer is PEG-acrylate. Methacrylated methyl ricinoleate was added as a hydrophobic structure and as a hydrophilic structure, FDA approved biocompatible PEG moiety was added. Castor oil was chosen for the hydrophobic block among other oil-derived compounds because it is cost-effective, readily available, and simple to functionalize. Thus, the polymer nanocarrier spontaneously formed as a micelle structure. Although it was dissolved in the solvent in which it was synthesized, when it was placed in aqueous media, micelle-based structures and a slightly opaque and stable dispersion were formed.

[0012] STEP 1 : SYNTHESIS

[0013] Methacrylated methyl ricinoleate (MMR) obtained from castor oil was used as a hydrophobic block, and as a hydrophilic block, Poly(ethylene glycol) (PEG) was used. 95 mg of MMR and 120 mg of mPEG-acrylate were dissolved in a suitable solvent. The said suitable solvents may be methanol, ethanol, dimethyl sulfoxide (DMSO), dimethylformamide (DMF) or the mixtures of these solvents in different proportions. Preferably, it was dissolved in DMF and 6 mg of photoinitiator was added. Dimethoxy-2-phenylacetophenone (DMPA) was preferably used as a photoinitiator, however, any photoinitiator that produces a radical source when exposed to UV-vis light can be used in alternative applications.

[0014] For a period ranging from 5 to 30 minutes, two acrylate-based monomers were subjected to polymerization under low energy (365 nm) UV light in the presence of a photoinitiator. As a result of polymerization, polymer chains dissolved in the polymer solution were obtained. When the obtained polymers were placed in an aqueous media, a micelle-based opaque nano- dispersion emerged. Polymer nanocarriers, which were dried in a lyophilizer under vacuum and at low temperatures were characterized.

[0015] STEP 2: CHARACTERIZATION

[0016] Figure 1A demonstrates the particle size distribution of the polymer nanogels synthesized with methacrylated methyl ricinoleate. Based on the results of the zetasizer size analysis, the average particle size was calculated to be 105.1 nm. In Figure IB, SEM images are demonstrated. Homogeneous, spherical, sample-based polymer nanocarriers are observed.

Claims

CLAIMS1. A nanocarrier, characterized in that it comprises i) methacrylated methyl ricinoleate and ii) at least one water-soluble polymer reagent having an acrylate group.

2. The nanocarrier according to Claim 1, characterized in that at least one water-soluble polymer reagent having an acrylate group is preferably poly(ethylene glycol) methyl ether acrylate (mPEG-acrylate).

3. A nanocarrier synthesis method according to Claim 1, characterized in that it comprises the following process steps: i. dissolving methacrylated methyl ricinoleate (MMR) and at least one water- soluble polymer reagent having an acrylate group in solvent, ii. adding a photoinitiator to the solution, iii. subjecting the solution to polymerization under UV light in the presence of a photoinitiator, iv. obtaining powdered nanocarriers by drying in a lyophilizer after the linear polymers obtained produce an opaque nano-dispersion with micelle structure in aqueous media.

4. A method for producing nanocarriers according to Claim 3, characterized in that the polymer reagent in step i. is mPEG-acrylate.

5. The method for producing nanocarriers according to Claim 3, characterized in that the solvents in step i. are methanol, ethanol, dimethyl sulfoxide (DMSO), dimethylformamide (DMF) or mixtures thereof in different ratios.

6. The method for producing nanocarriers according to Claim 5, characterized in that the solvent is preferably dimethylformamide (DMF).

7. The method for producing nanocarriers according to Claim 3, characterized in that dimethoxy-2-phenylacetophenone (DMPA) is added as a photoinitiator in step ii.

8. The method for producing nanocarriers according to Claim 3, characterized in that in step iii., the solution is subjected to polymerization under UV light having a wavelength of 365 nm.

9. The method for producing nanocarriers according to Claim 4, characterized in that in step i., 95 mg and 120 mg of mPEG-acrylate are dissolved in solvent.

10. The method for producing nanocarriers according to Claim 7, characterized in that in step ii., 6 mg dimethoxy-2-phenylacetophenone (DMPA) is added as a photoinitiator.

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