Study Of PH-responsive PEG-b-PCL-b-PAE Nanoparticle For Delivering Vancomycin To Subcutaneous Inflammation

For smart nanocarrers only few or no drugs are very slowly released under normal physiological environment. But when nanocarriers reach targeting sites, drugs are rapidly and persistently released, which as a result, contrubutes to achieving targeted drug delivery and controlled release. Slightly acidic environment of tumor periphery is one of the hotspots of targeted drug delivery. There were several domestic and international research applying charge reversal characteristic of nanocarriers to enhance drug delivery to tumor and achieving good research effect.Inflammation tissues have acidic environment like the tumor. So pH sensitive nanocarriers can be applied to enhance drug in vivo delivery. In the present study, considering the charge conversion characteristic of poly(β-amino ester), we designed and synthesized pH-responsive triblock copolymer polyethylene glycol-b-polycaprolactone-b-poly(β-amino ester) (PEG-PCL-PAE) and general two block copolymer polyethylene glycol-b-polycaprolactone (PEG-PCL) acting as carriers of vancomycin labelled with 6-carboxy rhodamine (TAMRA) for in vitro and in vivo study. The results showed:PEG-PCL and PEG-PCL-PAE were successfully synthesized through ring openning polymerization and Michael addition reaction, and by the use of self-assembly technique PEG-PCL and PEG-PCL-PAE micelles were obtained, furthermore, MTT experiment confirmed micelles had no effect on the growth and proliferation of NIH 3T3 and 293T; under pH 7.4, surfaces of micelles were negatively charged, but when the pH decreased to lower than 6.5, the surface of PEG-PCL-PAE became positively charged and the number of positive charges increased as pH decreasing; by the double solvent emulsion evaporation method, copolymers and vancoymcin respectively formed nanoparticles PEG-PCL/Van and PEG-PCL-PAE/Van, particle size of which were 53nm and 61nm; in vitro target study demonstated the combination of PEG-PCL-PAE/Van and MRS A was enhanced under pH 6.5, by the reason of protonation of PAE; in vivo fluorescence imaging results showd PEG-PCL-PAE as carrier of vancoymcin could extend the circulation time of drug and improve drug accumulation in site of skin inflammation.In this study, we used pH-responsive PAE with good stablity and biocompatiblity as drug carrier to delivery vancomycin in vitro and in vivo. The results showed that the polymer can effectively extend circulation time of vancomycin and enhance drug accumulation at the infection site. The characteristic of charge conversion makes PAE widely used in enhancing drug delivery to differenet types of inflammation caused by bacteria, which provides new ideas and methods for early diagnosis and treatment of inflammation.