Cell-Mimicking Chitosan-Based Polymeric Assembly For Drug Nanocarriers

In recent years, protecting the human being from damage by ionizing radiation gets more and more attention with the rapid development and application of nuclear technology. However, the real practical clinical drug is still very small though there have been many studies on radiation protection drugs. The main reason is the side effects, short half-life and low solubility of drugs. On the other hand, the research and development of peptide drugs has been widely involved in anticancer drugs, antiviral peptides, antimicrobial peptides, vaccines and cardiovascular drugs. However, the peptide drugs often have short half-life, and require multiple doses. Diffusion of the peptide drugs in vivo is poor and not easy to pass biological barriers. These drawbacks of peptide drugs bring inconvenience in use and limit their clinical applications.Many studies have found that the biodegradable polymer nanoparticles have good biocompatibility and long circulation time, and have been widely used in controlled drug delivery. Therefore, the polymer nanoparticles are expected to be used in the transportation aspects of radioprotection drugs and peptide drugs. In this work, we synthesized poly(sulfobetaine methacrylate)(PSBMA) grafted chitosan(CS) under γ-ray irradiation as nanocarriers to explore the possibility of its application in these two areas.Specific studies of this paper are as follows:(1) Ferulic acid loaded poly(sulfobetaine methacrylate)-grafted chitosan nanoparticles for effective protection from ionizing radiation.This chapter examines the effective protection of ferulic acid(FA) loaded chitosan-based nanocarriers for ionizing radiation. Specifically, PSBMA is grafted onto chitosan under γ-ray irradiation. Then FA is loaded into the copolymer assembly to get radiation protection drug nanoparticles. In vitro release tests show~88% of FA can be stably packaged for more than 8 h at 37 °C in PBS. Excitedly, radiation protection drug nanoparticles show radical scavenging activity of up to 93 %. FA retains its inherent antioxidant in CS-g-PSBMA nanocarrier. Pharmacokinetic experiments prove that the extension of the retention time in the circulation half-life is up to 10 h after FA is packaged in CS-g-PSBMA carrier. More importantly, the results of in vivo anti-radiation test show that CS(FA)-g-PSBMA nanoparticles have very more beneficial effects than pure FA in therapeutic efficacy for ionizing radiation mice compared to the pure drug. Thus, this work may open up a new way for drug carrier in the application field of radiation protection.(2) Synthesis of poly(sulfobetaine methacrylate)-grafted chitosan copolymer under γ-ray irradiation for alamethicin assembly.This chapter examines a biocompatible polymer assembly for supporting the antimicrobial membrane peptides-alamethicin. Specifically, monomer SBMA is grafted onto CS under γ-ray irradiation to synthesize graft polymer CS-g-PSBMA. The graft copolymer could self-assemble into the micelles in distilled water. MTT experiments show that the carrier is low cytotoxicity, and has good biocompatibility. The confocal microscopy figures prove that alamethicin can self-assemble with CS-g-PSBMA micelles in the water. It can be seen that the more alamethicin, the smaller sizes of the hybrid complex in the particle size distribution. Alamethicin remains secondary helical structures in the complex, exhibiting its biological activity. Electron spin resonance spectra show that alamethicin can penetrate into the hydrophobic core and hydrophilic shell of CS-g-PSBMA micelles. The results indicate that CS-g-PSBMA assemblies can be used as polypeptide drug carriers and to mimic lipid-membrane environments for peptide-membrane interactions.