title: An Injectable Gel Platform for the Prolonged Therapeutic Effect of Pitavastatin in the Management of Hyperlipidemia.
abstract: In this study, an injectable in situ-forming gel has been designed and fabricated for the controlled and prolonged release of pitavastatin calcium (Pit) for treating hyperlipidemia. By mixing phospholipids and soybean oil with ethanol, the phospholipid-based platform material (PSE) displayed in a sol state with low viscosity in vitro. After subcutaneous injection, pregel solution underwent rapid-phase separation and gelation in situ thus forming a drug release depot. Pit was loaded within PSE (PSE-P), which achieved prolonged release profiles for 15 consecutive days in vitro. Correspondingly, the pharmacokinetic study in rats demonstrated that PSE-P achieved sustained in vivo release for 15 days after 1 subcutaneous injection. The pharmacodynamic study in hyperlipidemia rats further revealed that the levels of total cholesterol, total triglyceride, and low-density lipoprotein decreased remarkably, and the in vivo therapeutic effect was well maintained for over 20 days. Additionally, PSE-P showed mild tissue inflammatory responses and excellent degradability in vivo. Thus, in situ-forming PSE-P gel represents a viable and promising drug delivery platform to achieve long-term therapeutic effects in the management of hyperlipidemia.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Nanxi
authors.initials: N
authors.lastname: Xiang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: He
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Jinjie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Sun
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: gongtaoy@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Gong
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery Systems, Ministry of Education, Department of Pharmaceutical Sciences, West China School of Pharmacy, Sichuan University, Chengdu 610041, China. Electronic address: yfu4@scu.edu.cn.
authors.forename: Yao
authors.initials: Y
authors.lastname: Fu
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000378:metabolism; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems / Q000379:methods*; D005782:Gels / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006949:Hyperlipidemias / Q000188:drug therapy* / Q000378:metabolism; D007279:Injections, Subcutaneous / Q000379:methods; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D011804:Quinolines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000378:metabolism; D014783:Viscosity
chemical_list: D003692:Delayed-Action Preparations; D005782:Gels; D008077:Lipoproteins, LDL; D011804:Quinolines; D014280:Triglycerides; D002784:Cholesterol; C108475:pitavastatin
keywords: hyperlipidemia; in situ–forming gel; phospholipids; pitavastatin; sustained release