Preparation and characterization of nanoparticles shelled with chitosan for oral insulin delivery.
Nanoparticles (NPs) composed of chitosan (CS) and poly(gamma-glutamic acid) (gamma-PGA) were prepared by a simple ionic-gelation method for oral insulin delivery. Fourier transform infrared (FT-IR) spectra indicated that CS and gamma-PGA were ionized at pH 2.5-6.6, while X-ray diffractograms demonstrated that the crystal structure of CS was disrupted after it was combined with gamma-PGA. The diameters of the prepared NPs were in the range of 110-150 nm with a negative or positive surface charge, depending on the relative concentrations of CS to gamma-PGA used. The NPs with a positive surface charge (or shelled with CS) could transiently open the tight junctions between Caco-2 cells and thus increased the paracellular permeability. After loading of insulin, the NPs remained spherical and the insulin release profiles were significantly affected by their stability in distinct pH environments. The in vivo results clearly indicated that the insulin-loaded NPs could effectively reduce the blood glucose level in a diabetic rat model.
Lin
Yu-Hsin
YH
Department of Chemical Engineering, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
Mi
Fwu-Long
FL
Chen
Chiung-Tong
CT
Chang
Wei-Chun
WC
Peng
Shu-Fen
SF
Liang
Hsiang-Fa
HF
Sung
Hsing-Wen
HW
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D018938:Caco-2 Cells; D002463:Cell Membrane Permeability; D048271:Chitosan / Q000737:chemistry* / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000008:administration & dosage*; D053758:Nanoparticles / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D051381:Rats; D014961:X-Ray Diffraction
D001786:Blood Glucose; D007328:Insulin; C511775:poly(gamma-glutamic acid); D011099:Polyglutamic Acid; D048271:Chitosan