A Precise Nano-drug Delivery System Adapted To "clinical Needs": Intelligent Design And Effect Evaluation

Nanoparticle-based drug delivery systems represent a type of drug-encapsulated carriers consisting of polymer micelles,liposomes,microemulsions,organic or inorganic nanoparticles,with the size less than 1000 nm.Compared with traditional drug delivery formulation,nanoparticle-based delivery systems render adjustable release kinetics,improved drug absorption and bioavailability,simultaneous transportation of multiple drug molecules and imaging reagents,targeted delivery to disease sites,and et al.Towards the goal of developing precision medicine,next generation of nano-drug delivery systems would be able to precisely locate at the disease site,sustainedly release drugs,and achieve tunable pharmacokinestics.In this thesis,we designed three precise nano-drug delivery systems,aiming to resolve three clinical challenges.Firstly,during the treatment of ulcerative colitis,drugs fail to reach the colon site effectively.To resolve this problem,we designed an orally “intelligent”capsule to precisely delive drugs at the colon site.The capsule include three layers,capable of programmable drgradation and long-term release of drugs at the colon site.Such a formulation dramatically enhanced the resident periods and drug concentrations at the colon site,thus reducing the systemic side effects and improving the treatment efficacy of ulcerative colitis.Secondly,for the treatment of heart failure after myocardial infarction,repeated injections of high concentration of drugs are needed in the clinic.We proposed to in situ injection of nanoparticles for sustained release of liraglutide in the myocardial infarction surgery.As liraglutide-encapsulated nanoparticles can sustainedly release for 28 days in the lesion,alleviate the heart failure effectively after myocardial infarction at the same time,reducing the system side effects caused by systemic administration,such as hypoglycemia.Finally,eriocalyxin B is a promising drug candidate for prostate cancer treatment,while its high hydrophobicity hinders the clinical translation.We constructed an eriocalyxin B-encapsulated nanoformulation,which improves the pharmacokinetics of eriocalyxin,thus dramatically enhancing its treatment efficacy for prostate cancer.