Preparation Of Polyaspartic Acid-poly(L-lactide-co-glycolide) Graft Copolymer And Its Targeting In Pulmonary Administration

Pulmonary administration is a form of administration that directly reaches the lung lesions.It can be applied not only to the lungs,but also following blood flow to achieve systemic administration.There are two problems with this "regionally targeted" administration of direct lung:the inhaled formulation meets the lung aerodynamic diameter requirements for lungs and is capable of depositing in the lungs,and is able to"accurately" target cancer cells.The targeting mechanism.The concentration of glutathione in cancer cells is much higher than that in normal cells.In this paper,a polylactic acid-glycolic acid(PASP)modified by biodegradable material polyaspartic acid(PASP)modified by linking disulfide bonds to the lungs is designed.PLGA)has a redox-sensitive amphiphilic polymer(PLGA-SS-PASP).The chemical structure was characterized by HNMR1,FTIR and other spectroscopic methods.The W/O/W double emulsification method and self-assembly method were investigated.The drug loading ability of doxorubicin and the optimal preparation process were confirmed.The in vitro release evaluation was performed by in vitro drug release experiments and cell experiments.In vitro drug release experiments showed that the release of the hydrophobic anticancer drug doxorubicin can be controlled by the carrier as the reducibility in the environment increases.Cytotoxicity experiments showed that PLGA-SS-PASP has no toxic side effects on human lung cancer cell A549 and normal hepatocyte QSC7701,while PLGA-SS-PASP/DOX loaded with doxorubicin has obvious toxic effects on A549 and no obvious toxic effects on QSC7701..At the same time,the results of apoptosis detection of A549 cells by flow cytometry can prove that drug-loaded nanoparticles can promote the apoptosis effect of doxorubicin on cancer cells,and the carrier itself has no biological toxicity.Finally,the lung inhalability of the carriers prepared by the two drugs was evaluated.It was confirmed that the carrier prepared by PLGA-SS-PASP was suitable for lungs by examining its aerodynamic size and distribution of lung deposition.Partial administration.At the same time,the physical properties and controlled release effects of the PLGA-SS-PASP/DOX after atomization were evaluated.The experiments showed that the atomization process had no significant effect on the stability and drug release effect of the carrier.