title: Effective mucoadhesive liposomal delivery system for risedronate: preparation and in vitro/in vivo characterization.
abstract: In this work, we aimed to develop chitosan-coated mucoadhesive liposomes containing risedronate to improve intestinal drug absorption. Liposomes containing risedronate were prepared with 1,2-distearoryl-sn-glycero-3-phosphocholine and distearoryl-sn-glycero-3-[phospho-rac-(1-glycerol)] using the freeze-drying method, with subsequent coating of the anionic surfaces of the liposomes with chitosan. The in vitro characteristics of the chitosan-coated liposomes were investigated, including their stability, mucoadhesiveness, and Caco-2 cell permeability. This formulation was stable in simulated gastric and intestinal fluids, with the percentage of drug remaining in the liposomes being more than 90% after 24 hours of incubation. Chitosan-coated liposomes also showed strong mucoadhesive properties, implying potential electrostatic interaction with the mucous layer in the gastrointestinal tract. Compared with the untreated drug, chitosan-coated liposomes significantly enhanced the cellular uptake of risedronate, resulting in an approximately 2.1-2.6-fold increase in Caco-2 cells. Further, the chitosan-coated liposomes increased the oral exposure of risedronate by three-fold in rats. Taken together, the results of this study suggest that chitosan-coated liposomes containing risedronate should be effective for improving the bioavailability of risedronate.
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Ilsan-Donggu, Goyang, Republic of Korea.
authors.forename: Il-Woo
authors.initials: IW
authors.lastname: Jung
authors.affiliation: College of Pharmacy, Dongguk University-Seoul, Ilsan-Donggu, Goyang, Republic of Korea.
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D065567:Absorption, Physiological; D000284:Administration, Oral; D000818:Animals; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000737:chemistry / Q000652:urine; D018938:Caco-2 Cells; D012968:Etidronic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry / Q000652:urine; D006801:Humans; D008081:Liposomes / Q000737:chemistry*; D008297:Male; D008657:Metabolic Clearance Rate; D009077:Mucins / Q000737:chemistry / Q000378:metabolism*; D065568:Oral Mucosal Absorption / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D008081:Liposomes; D009077:Mucins; D000068296:Risedronic Acid; D012968:Etidronic Acid
keywords: bioavailability; cellular uptake; chitosan; liposome; mucoadhesiveness