Preparation And Evaluation Of Reduced Sensitive Rice - Platinum Nano - Micelles

Based on the application and research of polymers as drug carriers. The design of polymeric carriers can be combined with the characters of cellular environment, for instance, stimuli-responsive carriers. The development of smart drug delivery system is a hot topic in the field of biomaterials.In this study, the pyrene terminated polymer- polyacrylic acid 2-(dimethylamino)ethyl(PDMAEA) with the disulfide linked and reduction-sensitive was synthesized by free radical addition fragmentation chain transfer polymerization(RAFT polymerization).Its structure was characterized by 1H NMR. PDMAEA micelles were obtained by direct water dissolution method. PDMAEA/ miriplatin micelles were preparaed by dialysis method with miriplatin as experimental drug. Pyrene, as a fluorescence probe, was used to determine critical micelle concentration(CMC). With the particle size, fluorescence intensity ratio(I338/I333) and morphology as the index, the level of DTT(10m M) in the tumor cells was simulated, and the sensitivity of the disulfide bonds was investigated. The particle size and potential of the micelles were determined by Malvern laser particle size analyzer, and the morphology of the micelles was observed by transmission electron microscope. Microporous membrane filter method was used to determine the entrapment efficiency(EE) and optimized the prescription craft. Dialysis method was used to study the release characteristics in vitro. The determination of toxicity of PDMAEA and PDMAEA/ miriplatin on Hep G2 cells by MTT. The location of endocytosis was obtained by rhodamine-b fluroscence probe labeling. The results showed that the successful synthesis of PDMAEA, and the CMC of PDMAEA was 6.90 μg/m L. The diameter were39±0.86 nm and 51.5±0.82 nm. Zeta potential were(1.24±0.08) m V and(0.891±0.11) m V.The micelles were showed regularly spherical, uniform size and the EE was(30.5 +0.35)%. For the redox-responsive behaviors of these micelles triggered by DTT evaluated from the changes of micellar size, I338/I333 and morphology. In vitro drug release profiles exhibited that the cumulative release amount reached about 81.8% with DTT at 5h, but the cumulative drug release amount was only about 10.5% without DTT even after 24 h,which was further illustrated that PDMAEA can respond to the high redox level intracelluar tumor cells and show instant release properties. MTT showed that the survival rate all above 50% within 0.1-3mg/m L, and IC50 was 90.625μg/m L. Compared with the miriplatin solution, the content of Pt in liver and tumor tissue of mice increased significantly(P < 0.05), the content of Pt in the kidneys decreased significantly(P < 0.05),which can effectively reduce the burden on the kidneys, and also has good passive targeting to liver and tumor. Therefore, the prepared PDMAEA/ rice platinum micelle can be used as a reduction sensitive intelligent drug carrier for the delivery of hydrophobic drugs.