title: Improved oral bioavailability of alendronate via the mucoadhesive liposomal delivery system.
abstract: This study aimed to design the chitosan coated liposomes of alendronate and optimize their in vitro/in vivo characteristics to improve the bioavailability as well as potentially to reduce the mucosal irritation of alendronate. Liposomes of alendronate were prepared with DSPC/DSPG by using thin layer film hydration method and then the surface of anionic liposomes was coated by chitosan. In vitro characteristics of liposomes (e.g., stability in various biological media, mucoadhesiveness and cellular uptake profiles) were evaluated along with the pharmacokinetic studies in rats. Lipid vesicles of 200 nm size were obtained with narrow size distribution (PI<0.1) and subsequently coated with chitosan. Chitosan coated liposomes were stable for 24 h without either size change or drug leakage in various biological fluids including simulated gastric fluids and intestinal fluids. Furthermore, it exhibited strong mucoadhesive properties. Compared to the untreated drug (non-liposome), the chitosan coated liposomes indicated significantly (p<0.05) increased cellular uptake of alendronate in Caco-2 cells and also 2.6-fold enhancement in oral bioavailability of alendronate in rats. Taken all together, the mucoadhesive liposomes for the oral delivery of alendronate was prepared by using DSPC and DSPG with narrow size distribution and appeared to be effective to enhance the bioavailability of alendronate in rats.
authors.affiliation: College of Pharmacy, Dongguk University, Pil-dong-3-ga, Jung-gu, Seoul 100-715, Republic of Korea. hkhan@dongguk.edu
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Shin
authors.forename: Dong Hoon
authors.initials: DH
authors.lastname: Ha
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D019386:Alendronate / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D000818:Animals; D001682:Biological Availability; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D004355:Drug Stability; D006801:Humans; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D009077:Mucins / Q000378:metabolism*; D053758:Nanoparticles; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D050071:Bone Density Conservation Agents; D008055:Lipids; D008081:Liposomes; D009077:Mucins; D010713:Phosphatidylcholines; D048271:Chitosan; C010942:1,2-distearoyllecithin; D019386:Alendronate