title: Liposomes coated with N-trimethyl chitosan to improve the absorption of harmine in vivo and in vitro.
abstract: In this study, harmine liposomes (HM-lip) were prepared through the thin-film hydration-pH-gradient method and then coated with N-trimethyl chitosan (TMC). Particle size, zeta potential, entrapment efficiency, and in vitro release of HM-lip and TMC-coated harmine liposomes (TMC-HM-lip) were also determined. Sprague Dawley rats were further used to investigate the pharmacokinetics in vivo. Retention behavior in mouse gastrointestinal tract (GIT) was studied through high-performance liquid chromatography and near-infrared imaging. Degradation was further evaluated through incubation with Caco-2 cell homogenates, and a Caco-2 monolayer cell model was used to investigate the uptake and transport of drugs. HM-lip and TMC-HM-lip with particle size of 150-170 nm, an entrapment efficiency of about 81%, and a zeta potential of negative and positive, respectively, were prepared. The release of HM from HM-lip and TMC-HM-lip was slower than that from HM solution and was sensitive to pH. TMC-HM-lip exhibited higher oral bioavailability and had prolonged retention time in GIT. HM-lip and TMC-HM-lip could also protect HM against degradation in Caco-2 cell homogenates. The uptake amount of TMC-HM-lip was higher than that of HM and HM-lip. TMC-HM-lip further demonstrated higher apparent permeability coefficient (P(app)) from the apical to the basolateral side than HM and HM-lip because of its higher uptake and capability to open tight junctions in the cell monolayers. TMC-HM-lip can prolong the retention time in the GIT, protect HM against enzyme degradation, and improve transport across Caco-2 cell monolayers, thus enhancing the oral bioavailability of HM.
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Wei-Liang
authors: WL
authors: Chen
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Zhi-Qiang
authors: ZQ
authors: Yuan
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Yang
authors: Y
authors: Liu
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Shu-di
authors: SD
authors: Yang
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Chun-ge
authors: CG
authors: Zhang
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Ji-Zhao
authors: JZ
authors: Li
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Wen-jing
authors: WJ
authors: Zhu
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Fang
authors: F
authors: Li
authors: Department of Radiobiology, College of Radiological Medicine and Protection, Soochow University, Suzhou, People's Republic of China; Changshu Hospital of Traditional Chinese Medicine, Changshu, People's Republic of China.
authors: Xiao-feng
authors: XF
authors: Zhou
authors: The Second Affiliated Hospital of Xinjiang Medical University, Urumqi, People's Republic of China.
authors: Yi-mei
authors: YM
authors: Lin
authors: Department of Pharmaceutics, College of Pharmaceutical Sciences, Soochow University, Suzhou, People's Republic of China.
authors: Xue-nong
authors: XN
authors: Zhang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D041981:Gastrointestinal Tract / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006247:Harmine / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D010316:Particle Size; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D004337:Drug Carriers; D008081:Liposomes; C118071:N-trimethyl chitosan chloride; D006247:Harmine; D048271:Chitosan
keywords: Caco-2 cell; TMC; bioavailability; harmine; liposomes