The Study Of Several Kinds Of Nano Materials As Drug And Gene Carriers

Nano materials are widely used as drug and gene carriers in the field of drug and gene delivery.There are three parts in this dissertation,including autophagy induced by cationic lipid and the effect of autophay on gene delivery efficiency mediated by cationic lipid;a synthetic peptide efficiently deliver gene into rat primary osteoblastic cells and PAMAM as drug carriers of NSAIDs.In partâ… ,we reported that autophagy did happen when cells were transfected using cationic lipid based reagents.Also,autophagy could be induced by cationic lipid only.Steady state study and flux measurements all proved that the autophagy induced by cationic lipid was completed and mTOR independent.Moreover,autophagy positively regulated gene delivery efficiency during cationic lipid mediated transfection.In partâ…¡,we synthesized a 15-amino acid bi-functional synthetic peptide,RPC2, with the sequence Ac-CGKRKWSQPKKKRKV-Cysteamide,which consists of a 7-amino acid nuclear localization signal(NLS) domain at the carboxyl terminus that electrostatically binds DNA and a 5-amino-acid tumor-homing domain at the amino terminus.This peptide efficiently delivered GFP and Renilla luciferase reporter genes into rat primary osteoblastic cells while exhibiting low cytotoxicity.The optimal delivery was achieved when the ratio of DNA:RPC2 reached 1:10(w/w). Transfection efficiency could be further enhanced by the addition of Lipofectamine 2000 and modification of RPC2.These results indicated that RPC2 could deliver exogenous DNA into primary osteoblastic cells with low cytotoxicity and be potentially utilized in experimental and clinical applications in the field of bone tissue engineering.In partâ…¢,we investigated the potential of polyamidoamine(PAMAM) dendrimers as drug carriers of ketoprofen by in vitro and in vivo studies.The in vitro and in vivo study all suggested that the release of ketoprofen from the drug-dendrimer complex was significantly slower compared to pure ketoprofen.Anti-nociceptive studies using the acetic acid-induced writhing model in mice showed a prolonged pharmacodynamic behavior for the ketoprofen-PAMAM dendrimer complex.Moreover,we have assessed the ability of polyamidoamine(PAMAM) dendrimers to facilitate transdermal delivery of NSAIDs,using Ketoprofen and Diflunisal as model drugs.The complexes formed by NSAIDs and PAMAM had a prolonged pharmacodynamic profile and a higher blood drug level.All these results demonstrated that PAMAM dendrimers might be considered as a potential drug carrier of NSAIDs.