title: Effects of degree of quaternization on the preparation and characterization of insulin-loaded trimethyl chitosan polyelectrolyte complexes optimized by central composite design.
abstract: The aim of the present study was to investigate the effects of varying degrees of quaternization (DQ: 22, 35 and 41%) on the preparation and characterization of insulin (INS)-loaded polyelectrolyte complexes (PECs) prepared by N-trimethyl chitosan chloride (TMC). A two factor-five level central composite design was used for the optimization. The concentrations of INS and TMC were defined as independent variables, while the entrapment efficiency (EE%) and loading efficiency (LE%) as dependent variables. The three optimized INS-TMC PECs were characterized for their size, zeta potential, EE% and LE%. The morphology and electrostatic interaction of PECs were evaluated. Then, the stability in the enzyme solution and in vitro release as well as mucoadhesive properties of the three PECs were all investigated. The results showed that the size and EE% of the optimum formulations were significantly decreased using TMC of higher DQ, while the zeta potential and LE% were slightly influenced by DQ. The stability assay exhibited partial protection of TMC PECs, and the better protective effect was observed for PECs of higher DQ. The in vitro release study presented different initial and sustained release behaviors of INS-TMC PECs and the mucin adsorption study confirmed a positive correlation between the DQ and the mucoadhesive property of PECs.
authors.affiliation: Key Laboratory of Drug Targeting and Drug Delivery, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Jin
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Zhu
authors.forename: Xiao-Ran
authors.initials: XR
authors.lastname: Wang
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000269:Adhesives / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D015195:Drug Design; D004355:Drug Stability; D004573:Electrolytes / Q000737:chemistry; D007328:Insulin / Q000008:administration & dosage / Q000737:chemistry*; D009077:Mucins / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D012995:Solubility; D055672:Static Electricity
chemical_list: D000269:Adhesives; D004337:Drug Carriers; D004573:Electrolytes; D007328:Insulin; D009077:Mucins; C118071:N-trimethyl chitosan chloride; D048271:Chitosan