Mixed Micelles Formed By PDEAEMA-PPEGMA And PCL-PPEGMA For Application In Controlled Drug Release

Based on the difference between the pH value of tumor cells and normal human tissue cells,the pH-responsive copolymer for anticancer drugs delivery is one of the research hotspots in the field of drug controlled release.Although some progress has been made in the research of drug-loading systems,there are still some shortcomings in drug loading content and so on.In recent few years,mixed micelles self-assembled from two or more dissimilar block copolymers provide a direct and convenient approach to improve physical stability and enhance drug loading capacities of conventional polymeric micelles for drug delivery.Through the careful selection and blending of structurally and/or functionally diverse block copolymers,a population of novel and multi-functional micelles bearing desirable attributes of each constituent copolymer can be easily fabricated without the need for elaborate synthetic schemes and analogizedIn this paper,the well-designed PDEAEMA₃₀-PPEGMA₁₅,PCL₆₀-PPEGMA₂₀PCL₆₀-PPEGMA₁₅ and PCL₆₀-PPEGMA₁₀ copolymers were successfully synthesized,and their self-assembled mixed micelles are applied for anti-cancer drug controlled delivery.The structures of the synthesized copolymers were characterized and confirmed by nuclear magnetic resonance spectroscopy?¹H NMR?,FT-IR,gel permeation chromatography?GPC?.The CMC values of the amphiphilic polymers PCL₆₀-PPEGMA₂₀,PCL₆₀-PPEGMA₁₅,and PCL₆₀-PPEGMA₁₀ were 1.00 mg/L,0.91 mg/L,and 0.87 mg/L,respectively,and the CMC value of the pH-responsive block polymer PDEAEMA₃₀-PPEGMA₁₅ is 2.20 mg/L.The CMC values of mixed polymers MIX1,MIX2,MIX3 were 1.58 mg/L,1.45 mg/L and 1.38mg/L,suggesting their superior stability in neutral conditions.The partical sizes and Zeta potentials of blank mixed micelles on different pH values measured by Dynamic Light Scattering?DLS?testified that the micelles have pH-responsive behavior.And the drug loading content?LC?and entrapment efficiency?EE?achieved were 31.23%and 59.37%?MIX1?,26.53%and 54.46%?MIX2?,23.36%and 50.65%?MIX3?,respectively,indicated high drug loading capacity of these mixed micelles.The in vitro DOX release profiles of these mixed micelles demonstrated their good pH-responsive behavior,which provided good stability and less leakage at pH 7.4 and accelerated drug release behavior with little initial burst at pH 5.0.And cell cytotoxicity tests showed that the polymer PDEAEMA-PPEGMA and the blank mixed micelles have good biocompatibility,and the cytoxicity of drug-loaded micelles exhibited good antitumor efficacy to HepG2 cells.In summary,the mixed micelles obtained in this study exhibiting good stability and less leakage in neutral conditions and accelerated drug release behavior with little initial burst in slight acidic conditions,it shows that the drug-loaded mixed micelles self-assembled from the two polymers PDEAEMA-PPEGMA and PCL-PPEGMA might be a prospective candidate as anticancer drug delivery carrier with well-controlled release.