title: Chitosan-NAC nanoparticles as a vehicle for nasal absorption enhancement of insulin.
abstract: The purpose of this work was to investigate chitosan-N-acetyl-L-cysteine (chitosan-NAC) nanoparticles as a potential carrier system for the nasal delivery of insulin. For the study, we used insulin-loaded chitosan-NAC nanoparticles (140-210 nm in diameter) prepared by in situ gelation with tripolyphosphate (TPP), with positive zeta potential values of +19.5-31.7 mV and insulin loading capacities of 13-42%. The physicochemical properties of the nanoparticles were affected by the number of thiol groups present. Mucoadhesive properties, which were evaluated by measuring the in vitro absorbed mass of mucin, of chitosan-NAC nanoparticles were >1.8-fold that of unmodified chitosan nanoparticles. In aqueous solution, chitosan-NAC nanoparticles exhibited fast swelling behavior. Insulin was released from chitosan-NAC nanoparticles in vitro in an initial burst followed by slow release. Intranasal administration of chitosan-NAC nanoparticles in rats enhanced the absorption of insulin by the nasal mucosa compared with unmodified chitosan nanoparticles and control insulin solution. In light of these observations, the novel thiolated chitosan nanoparticles represent a promising vehicle for nasal insulin administration.
authors.affiliation: The Key Laboratory of Functional Polymer Materials of Ministry Education, Institute of Polymer Chemistry, Nankai University, Tianjin 300071, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Zheng
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Wu
authors.forename: Dayong
authors.initials: D
authors.lastname: Teng
authors.forename: Xinge
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.forename: Chaoxing
authors.initials: C
authors.lastname: Li
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D002448:Cell Adhesion; D048271:Chitosan / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009077:Mucins / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D011122:Polyphosphates / Q000737:chemistry; D051381:Rats; D013055:Spectrophotometry, Infrared; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013499:Surface Properties
chemical_list: D007328:Insulin; D009077:Mucins; D011122:Polyphosphates; D013438:Sulfhydryl Compounds; D048271:Chitosan; C005692:triphosphoric acid; D000111:Acetylcysteine