Preparation, characterization, and oral delivery of insulin loaded carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles.
To improve the efficiency of insulin via oral administration, pH-sensitive carboxylated chitosan grafted poly(methyl methacrylate) nanoparticles (CCGN) were prepared. CCGN were characterized by (1)H NMR, dynamic light scattering, zeta potential, and transmission electron microscopy, and the hypoglycemic effect of insulin loaded CCGN via the oral route was evaluated in normal and diabetic rats. CCGN exhibited a homogeneous morphology and a spherical shape with core-shell structure. They were aggregated in simulated gastric fluid while separated in simulated intestinal fluid. Insulin was mainly located in the shell of the CCGN via hydrogen bonding, electrostatic interaction, and Van der Waals force. Insulin release from the CCGN exhibited a pH-sensitive property in that it had a slow release rate at pH 2.0 and a fast release rate at pH 6.8 and 7.4. The pharmacological bioavailability after oral administration of insulin loaded CCGN at a dose of 25 IU/kg was found to be 9.7%. Besides, CCGN showed desirable tissue and blood compatibility. Therefore, the CCGN would be a promising delivery carrier for protein drugs via the oral route.
Cui
Fuying
F
State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200433, China.
Qian
Feng
F
Zhao
Ziming
Z
Yin
Lichen
L
Tang
Cui
C
Yin
Chunhua
C
D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials / Q000008:administration & dosage / Q000737:chemistry; D001786:Blood Glucose / Q000187:drug effects; D048271:Chitosan / Q000008:administration & dosage* / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry*; D016503:Drug Delivery Systems; D006860:Hydrogen Bonding; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D008422:Materials Testing; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D019904:Polymethyl Methacrylate / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D013499:Surface Properties; D013997:Time Factors
D001672:Biocompatible Materials; D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; D019904:Polymethyl Methacrylate; D048271:Chitosan