| In recent years, the bacterial drug resistance gradually receives widespread attention due to the irrational use of antibiotics. Antimicrobial peptides(AMPs) are excellent candidates as antimicrobial agents because of their significant inhibitory action on a broad spectrum of pathogenic microorganisms. However, the short half-life and bad enzymatic stability may prevent their applications in clinic. On the other hand, the rapid development and application of nuclear technology could bring about the increasing rise of environmental radioactivity level, which cause serious influence on people’s health. However, there are short biological efficacy and severe side effects for most of the radioprotection agents, which is difficult to meet the clinical requirements. Therefore, it is important to find effective drug systems for antibacterial activity and radiation protection in the biomedical fields.Previous work indicates that amphiphilic copolymers are able to form cell-like membranes and vesicles, and have attracted a great deal of interest. Polymeric systems with good stability and durability are designed to meet biomedical applications, which can reduce cell toxicity and improve drug bioavailability for targeted therapy, and so on. Therefore, functional polymeric carrier is expected to circumvent the restriction of antimicrobial peptides and radioprotection drugs. In this thesis, we have synthesized two kinds of biocompatible polymer carrier by random copolymerization and irradiation polymerization, respectively, and we explored the potential application in antibacterial treatment and radiation protection.Specific studies of the paper are as follows:(1) Alamethicin entrapped by a thermo-sensitive polymeric carrier Poly(AEM-co-SBMA) for enhanced antibacterial activity against microbial strainsThis chapter shows an effective approach for enhanced antibacterial activity of alamethicin against microbial strains by a thermo-sensitive polymeric carrier. Specifically, the amphiphilic copolymer, poly(2-(adenine-9-yl) ethanol methacrylate-co-sulfobetaine methacrylate)(poly(AEM-co-SBMA)) with UCST was successfully synthesized via radical copolymerization, and could self-assemble into micelles in distilled water at room temperature. Due to amphiphilic structure, alamethicin assembled with poly(AEM-co-SBMA) micelles well, and remained functional α-helical structure in the complex system. The copolymer can provide a low toxic carrier for alamethicin, and assembly complex has better enzymatic stability. The antibacterial activity of assembly complex was significantly more higher than free alamethicin, which may be ascribed to the rapid release of alamethicin from polymeric carrier above UCST. The released alamethicin was evenly distributed with high concentration in the media, thereby killing bacteria effectively. This work may provide a promising method for effective treatment of bacterial infections in clinic.(2) Probucol-loaded poly(2-methacryloyloxyethyl phosphorylcholine)-grafted chitosan nanoparticles for effective radioprotectionThis chapter shows a method for effective radioprotection of Probucol entrapped by chitosan-based nanocarrier. Specifically, chitosan graft copolymer(CS-g-PMPC) is first synthesized under γ-ray irradiation, and could self-assemble into the micelles in distilled water. Antioxidant Probucol is loaded into the core of the micelles with hydrophobic interaction. The drug nanoparticles are stable in PBS and well dispersed. Probucol is seriously toxic to HDF cells when the concentration is higher than 500 μM, while the drug nanoparticles show low toxicity due to the biocompatible polymeric carrier. Probucol reserves its inherent strong antioxidant in CS-g-PMPC nanoparticles, and shows an enhanced protection over cells against radiation-induced reduction of the cell viability in a dose-dependent manner. These results indicate that probucol-loaded CS-g-PMPC may portray a promising application for radiation protection in clinic. |
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