Olive oil-based biocompatible polymer nanocarriers and their production

Abstract

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

Description

[0001] OLIVE OIL-BASED BIOCOMPATIBLE POLYMER NANOCARRIERS AND THEIR PRODUCTION

[0002] Technical Field

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

[0004] State of the Art (Background)

[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 Objectives of the Invention

[0007] With the present invention, unique nanocarriers have been developed to transport 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] These nanocarriers were synthesized using oleyl methacrylate derived from olive oil and PEG-acrylate. Oleyl methacrylate was added as a hydrophobic structure and as a hydrophilic structure, the FDA-approved biocompatible PEG group was added. 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. In addition, 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.

[0009] Description of the Figures

[0010] Figure 1. A) Particle size analysis of polymer nanocarriers; B) SEM image of polymer nanocarriers

[0011] Figure 2. Agarose gel electrophoresis images of the encapsulation of pDNA with Nano-OM. 1) pDNA-loaded sample bands with concentrated nano-OM concentration and 2) pDNA- loaded sample bands with dilute nano-OM concentration. 3) concentrated and 4) dilute nano- OM bands without pDNA loaded as control.

[0012] Detailed Description of the Invention

[0013] 1ST STEP: SYNTHESIS

[0014] Oleyl methacrylate (OM) derived from olive oil, the plant oil based monomer source, was used as the hydrophobic block and Poly(ethylene glycol) (PEG) was preferably used as the hydrophilic block. N-Isopropylacrylamide (NIP AM) and its derivatives can also be used as hydrophilic block monomer in alternatives of the invention. Poly(ethylene glycol) methyl ether acrylate (mPEG-acrylate) was provided from Sigma Aldrich. 1 mmol OM and 1 mmol mPEG-acrylate were dissolved in a suitable solvent (these solvents can be methanol, ethanol, dimethyl sulfoxide (DMSO) or mixtures of these solvents in different proportions) and 3% (w / w) photoinitiator was added to the solution. Dimethoxy-2-phenylacetophenone (DMPA) was preferably used as photoinitiator, however, any photoinitiator that produces a radical source when exposed to UV-vis light can be used in alternative applications. Two acrylate- based monomers were subjected to polymerization in the presence of a photoinitiator under low-energy (365 nm) UV light. As a result of polymerization, polymer chains dissolved in the polymer solution were obtained. When the obtained polymers were placed in an aqueous media, an opaque nano-dispersion emerged. Polymer nanocarriers, which were dried in a lyophilizer under vacuum (0.1 bar pressure) and low temperature (between -40°C and -60°C) were characterized. 2ND STEP: CHARACTERIZATION

[0015] Figure 1 A shows the particle size distribution of polymer nanocarriers synthesized with oleyl methacrylate. Based on the results of the zetasizer size analysis, the average particle size was calculated to be 39.8 nm. In Figure IB, SEM images are shown. Homogeneous, spherical, micellar-based polymer nanocarriers are observed.

[0016] Plasmid DNA was loaded into the obtained polymer nanocarriers, and the loading process was tested via electrophoresis studies (Figure 2). With polymer nanocarriers, carrying genetic material (DNA, RNA, etc.), drug molecules or biomolecules will be possible.

Claims

CLAIMS1. A nanocarrier, characterized in that it comprises at least one water-soluble polymer reagent having i) oleyl methacrylate (OM) and ii) acrylate group.

2. The nanocarrier synthesis method 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 method of producing a nanocarrier according to Claim 1, characterized in that it comprises the following process steps; i. Dissolving OM and at least one water-soluble polymer reagent having 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. Placing obtained linear polymers in aqueous media to produce an opaque nanodispersion with micelle structure and then drying in a lyophilizer in order to obtain nanocarriers in powder form.

4. The 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 in step ii, dimethoxy-2-phenylacetophenone (DMPA) is added as a photoinitiator.

6. 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.

7. The method for producing nanocarriers according to Claim 4; characterized in that in step i., 1 mmol OM and 1 mmol mPEG-acrylate are dissolved in solvent.

8. The method for producing nanocarriers according to Claim 3 or 5, characterized in that in step ii., 3 wt.% photoinitiator is added.

9. The method for producing nanocarriers according to Claim 3, characterized in that in step iv., the nanocarrier is dried under 0.1 bar pressure and between -40°C and -60°C.

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