title: In vitro and in vivo evaluation of chitosan graft glyceryl monooleate as peroral delivery carrier of enoxaparin.
abstract: In this paper a novel copolymer, chitosan graft glyceryl monooleate (CS-GO) was synthesized and its potential as the nanocarrier for enhancing the peroral delivery of enoxaparin was studied systemically. The successful synthesis was characterized by (1)H NMR. Enoxaparin nanocomplexes were prepared by self-assembly. Mucoadhesive properties of the nanocomplexes were evaluated using mucin particle method. Uptake and transport of the nanocomplexes were investigated in Caco-2 cells. In vivo absorption was studied in rats. The therapeutic effects of the nanocomplexes were evaluated using pulmonary thromboembolism model in mice. This study demonstrated that compared to chitosan based system, hydrophobic modification of CS with GO enhanced the oral absorption of enoxaparin significantly, which is in good agreement with the enhanced mucoadhesion, cellular internalization and transport in cell culture. Cellular uptake of CS-GO based enoxaparin nanocomplexes was incubation time, enoxaparin concentration and incubation temperature dependent. The uptake mechanism was assumed to be adsorptive endocytosis via clathrin- and caveolae-mediated process. Its therapeutic efficacy was further demonstrated by pharmacodynamic study with pulmonary thromboembolism inhibition percentage 47.1%. In conclusion, CS-GO copolymer is a promising nanocarrier for enhancing the oral absorption of enoxaparin.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Ding
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Xiaopin
authors.initials: X
authors.lastname: Duan
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Mahidol University, 447 Sri-Autthaya, Rajathavee, Bangkok 10400, Thailand.
authors.forename: Varaporn B
authors.initials: VB
authors.lastname: Junyaprasert
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China. Electronic address: maoshirui@syphu.edu.cn.
authors.forename: Shirui
authors.initials: S
authors.lastname: Mao
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018938:Caco-2 Cells; D048271:Chitosan / Q000737:chemistry*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D017984:Enoxaparin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005989:Glycerides / Q000737:chemistry*; D006801:Humans; D008297:Male; D008815:Mice, Inbred Strains; D015394:Molecular Structure; D010316:Particle Size; D011655:Pulmonary Embolism / Q000517:prevention & control; D017207:Rats, Sprague-Dawley; D013499:Surface Properties
chemical_list: D000925:Anticoagulants; D004337:Drug Carriers; D017984:Enoxaparin; D005989:Glycerides; D048271:Chitosan; C005953:monoolein
keywords: Chitosan; Enoxaparin; Glyceryl monooleate; Oral; Polyelectrolyte nanocomplexes