title: Enhanced systemic exposure of fexofenadine via the intranasal administration of chitosan-coated liposome.
abstract: The present study aimed to develop the intranasal delivery system of fexofenadine for the prolonged drug release via the preparation of mucoadhesive liposome. By using thin layer film hydration method, liposome of fexofenadine was prepared with DPPC/DPPG, resulting in the small lipid vesicles (359 ± 5.5 nm) with narrow size distribution (PI<0.1). Subsequently, the surface of anionic liposome was coated by chitosan and in vitro characteristics of liposomes were evaluated along with the pharmacokinetic studies in rats. Chitosan coated liposomes were stable for 6-month storage at 4 °C without any significant size change and drug leakage. Furthermore, it exhibited strong mucoadhesive properties in mucin adsorption test, which was 3-fold higher than uncoated liposomes. Compared to the oral delivery of powder formulation, the intranasal delivery of fexofenadine significantly (p<0.05) increased systemic exposure of fexofenadine in rats. Particularly, the intranasal administration of chitosan coated liposome exhibited approximately 5 fold enhancement of AUC with more sustained drug release in rats compared to the oral delivery. In conclusion, intranasal administration of chitosan coated liposome appeared to be effective to enhance the bioavailability as well as prolonged exposure of fexofenadine in rats.
authors.affiliation: College of Pharmacy, Dongguk University, Pil-dong-3-ga, Jung-gu, Seoul 100-715, Republic of Korea.
authors.forename: Fu
authors.initials: F
authors.lastname: Qiang
authors.forename: Hyun-Jae
authors.initials: HJ
authors.lastname: Shin
authors.forename: Beom-Jin
authors.initials: BJ
authors.lastname: Lee
authors.forename: Hyo-Kyung
authors.initials: HK
authors.lastname: Han
mesh_terms: D000268:Adhesiveness; D000281:Administration, Intranasal; D000284:Administration, Oral; D000327:Adsorption; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000737:chemistry; D003692:Delayed-Action Preparations; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry; D004339:Drug Compounding; D039563:Histamine H1 Antagonists, Non-Sedating / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes; D008297:Male; D009077:Mucins / Q000378:metabolism; D053758:Nanoparticles; D010316:Particle Size; D010715:Phosphatidylglycerols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods; D016593:Terfenadine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D003692:Delayed-Action Preparations; D039563:Histamine H1 Antagonists, Non-Sedating; D008055:Lipids; D008081:Liposomes; D009077:Mucins; D010715:Phosphatidylglycerols; D016593:Terfenadine; D048271:Chitosan; D002784:Cholesterol; C093230:fexofenadine; D004134:Dimyristoylphosphatidylcholine; C030345:1,2-dipalmitoylphosphatidylglycerol