title: Exploration of hydrophobic modification degree of chitosan-based nanocomplexes on the oral delivery of enoxaparin.
abstract: The objective of this paper is to elucidate the influence of lipophilic modification degree of chitosan on the peroral absorption of enoxaparin. A series of novel chitosan grafted glyceryl monostearate (GM) copolymers with different GM substitution degree were synthesized and the successful synthesis was confirmed by (1)H NMR, FTIR and X-ray diffraction. Enoxaparin loaded nanocomplexes with different carriers were prepared by self-assembly process. Influence of GM substitution degree and chitosan molecular weight in the copolymer on the properties of the nanocomplexes was investigated. Morphology of the nanocomplexes was observed by atomic force microscopy. Mucoadhesive properties of the nanocomplexes were characterized using mucin particle method. Initially, mucoadhesion of the nanocomplexes increased with the increase of GM substitution degree and it started to decrease when the substitution degree was up to 18.6%. A good linear relationship between GM substitution degree and in vivo absorption of enoxaparin in fasted rats was established in the substitution degree range of 0-11.1%. In agreement with mucoadhesion data, further increasing GM substitution degree to 18.6% caused a decrease in oral absorption. In conclusion, oral bioavailability of enoxaparin can be enhanced by structure modification of the carriers and the bioavailability is hydrophobic modification degree dependent.
authors.affiliation: School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Wang
authors.forename: Liang
authors.initials: L
authors.lastname: Li
authors.forename: Yujiao
authors.initials: Y
authors.lastname: Sun
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Conghao
authors.initials: C
authors.lastname: Li
authors.forename: Varaporn B
authors.initials: VB
authors.lastname: Junyaprasert
authors.forename: Shirui
authors.initials: S
authors.lastname: Mao
mesh_terms: D000268:Adhesiveness; D000284:Administration, Oral; D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D017984:Enoxaparin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D005989:Glycerides / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D009077:Mucins / Q000737:chemistry; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D010314:Partial Thromboplastin Time; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000925:Anticoagulants; D004337:Drug Carriers; D017984:Enoxaparin; D005989:Glycerides; D009077:Mucins; C048159:glyceryl monostearate; D048271:Chitosan
keywords: Chitosan; Enoxaparin; Glyceryl monostearate; Oral; Polyelectrolyte nanocomplexes