Preparation And Performance Of PEG-vegetable Oil-PEG Y-shaped Amphiphilic Polymers Drug Carriers

With the depletion of petroleum resources and the increasing awareness of environmental protection,the utilization of renewable resources to prepare environmentally friendly polymers is receiving increasing attentions in academic settings.Due to their relatively low price,wide availability and biodegradable,vegetable oils are one of the most promising substitutes for petroleum to prepare polymers.Therefore,the use of vegetable oils to prepare polymers has attracted great interest.The long alkyl chain in vegetable oil has strong hydrophobicity and can be used as a hydrophobic block.By introducing hydrophilic polyethylene glycol(PEG),polymers not only retain the excellent properties of vegetable oils,but also exhibit amphiphilic properties.They can self-assemble into nanomicelles in aqueous solution and be used as drug carriers.Recent studies showed that Y-shaped amphiphilic polymers can effectively improve drug loading and release rate,in vivo circulation and biodistribution due to their unique structure.Therefore,two types of PEG-vegetable oil-PEG Y-shaped amphiphilic polymer drug carriers were designed and prepared,which consisting of monomethoxy poly(ethylene glycol)(mPEG)as hydrophilic segment,hydroxylated tung oil(HTO)and glyceryl monostearate(GMS)as hydrophobic block,respectively.Furthermore,their drug loading and release properties were studied.The main contents and conclusions are as follows:(1)PEG-HTO-PEG Y-shaped amphiphilic polymers consisting of HTO as hydrophobic block and mPEG as hydrophilic segment were prepared by a step-wise polymerization method using hexamethylene diisocyanate(HDI)as the linker.By adjusting the M_n of mPEG,three kinds of polymers with different mPEG lengths and the same HTO length were produced.FTIR,~1H NMR and GPC results confirmed the synthesis of target products;The thermal properties were characterized by DSC and TG.The results showed that the melting point of the prepared amphiphilic polymer increased with the increase of the M_n of mPEG,while the thermal stability had no obvious difference.PEG-HTO-PEG Y-shaped amphiphilic polymer micelles were prepared by dialysis method.The critical micelle concentration(CMC)of the polymer was determined by fluorescence probe method.It was found that the CMCs of the polymers increased with the increase of the M_n of mPEG in a range from 7.28to 11.73 mg/L.The laser particle size analyzer and TEM results revealed that the prepared micelles were almost spherical and well dispersed,and average hydrodynamic diameter about 150-190 nm.The particle size decreased with increase of the M_n of mPEG.The drug loading and in vitro release behavior were investigated using prednisone acetate as the model drug.The results indicated that the micelles could effectively load hydrophobic prednisone acetate and had a significant sustained release effect.The drug loading rate,encapsulation efficiency and release rate decreased with increase of the M_n of mPEG.Cell cytotoxicity tests showed that the PEG-HTO-PEG Y-shaped amphiphilic polymers were low nontoxic to L929 and HeLa cells.Among the three kinds of prepared PEG-HTO-PEG Y-shaped amphiphilic polymer micelles,PEG-HTO-PEG550 micelles were the best drug-loaded polymer system because of its highest drug loading capacity and the lowest critical micelle concentration.(2)Based on the results of the above system,PEG-GMS-PEG550 Y-shaped amphiphilic polymer was prepared by a stepwise polymerization using GMS as hydrophobic,mPEG(M_n=550)as hydrophilic segments,and HDI as the linker.FTIR,~1H NMR,GPC and DSC results confirmed the synthesis of target products.The self-assembly behavior of the polymer in aqueous solution was studied by laser particle size analyzer and TEM.The results showed that the PEG-GMS-PEG550Y-shaped amphiphilic polymer could self-assemble into spherical micelles with a diameter of 80 nm in aqueous solution.The CMC of the polymer determined by fluorescence probe techniques was 5.65 mg/L.The drug loading and in vitro drug release experiments showed that PEG-GMS-PEG550 micelles could effectively load hydrophobic prednisone acetate and had a significant sustained release effect.The drug loading rate and encapsulation efficiency of PEG-GMS-PEG550 micelles were13.2%and 33.1%,respectively.The cummulative release rates of drug-loaded micelles in pH=7.4 and pH=5.8 phosphate buffer at 180 h were 32.4%and 34.2%,respectively.Cell cytotoxicity experiments showed that the PEG-GMS-PEG550Y-shaped amphiphilic polymer was nearly no toxicity to L929 and HeLa cells.In summary,we successfully prepared PEG-HTO-PEG and PEG-GMS-PEG550Y-shaped amphiphilic polymers,which have potential application prospects as drug carriers.