The Preparation And Characterization Of DOX-loaded Micelle Based On Poly(γ-glutamic Acid)

Cancer has been a tremendous threat to human life and health. Chemotherapy is a main therapeutic approach for the treatment of many solid tumors. Micelle, as a widely used drug carrier, have solved the low bioavailability of most hydrophobic chemotherapeutic drugs and reduced the side effect due to their non-targeting property.As a natural polymer, poly(γ-glutamic acid)(γ-PGA) could not only meet the requirement for excellent drug carrier matrix, but also be specifically recognized by γ-glutamyl transferase(GGT), which is a receptor over-expression on the membrane of most tumor cells. This property helps the γ-PGA-based drug carrier uptake by tumor cells, leading to an improved therapeutic efficacy. It has been reported that γ-PGA-based gene carrier could be recognized by GGT, which exhibited enhanced cellular uptake and highly gene transfection efficiency. In this paper, we firstly studied the γ-PGA-based chemotherapeutic drug carrier, γ-PGA-g-PLLA, which encapsulated DOX. mPEG-PLGA is a commonly used carrier, compared with it, γ-PGA-based drug carrier showed higher uptake by hepatic carcinoma cells, that was in favour of its accumulation at tumor site. We also studied the cellular uptake pathway of γ-PGA-based drug carrier through a qualitative and semi-quantitatively analysis. The results confirmed that γ-PGA-based drug carrier was taken through a GGT-mediated process. Furthermore, this kind of drug carrier showed a pH sensitive in vitro DOX release, which could has a faster drug release in the acid condition of tumor site than in normal tissue.The formation of micelle is a dynamic process, which leads to an unstable structure of the micelle. A stereocomplexation could form by the equal molar mixture of PLLA and PDLA. The introduction of this stereocomplexation to the preparation of micelle helps to enhance its stability. In this paper, we prepared a stereocomplexed micelle using γ-PGA-g-PLLA and γ-PGA-g-PDLA. This stereocomplexed micelle exhibited a lower CMC than single γ-PGA-g-PLLA and γ-PGA-g-PDLA micelle. Furthermore, it also showed a higher drug loading content, higher drug loading efficiency, and slower in vitro drug release.The treatment of cancer is of crucial importance, and the diagnosis of cancer should also be overlooked. In the traditional cancer therapy, treatment and diagnosis are two independence processes, which undoubtedly enhance the pain and pay for patients. Theranostic nanomedicine is a collective system of diagnosis, delivery targeted therapy and monitoring the response to therapy, which brings dawn to cancer patients. In this paper, we designed and prepared a theranostic micelle by using the nanotechnology. The chemotherapeutic drug(DOX) and MRI contrast agent(SPIO) were encapsulated in the inner core of the micelle. We studied the magnetic property, MR image property, in vitro DOX release, cell cytotoxicity, and the cellular uptake of this theranostic nanomedicine. The results showed that this nanomedicine could not only meet its application in clinic, but also exhibited a faster DOX release in the tumor site. This micelle could have a potential application in the treatment and diagnosis of cancer.