Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of insulin.
OBJECTIVE
Colloidal metallic systems have been recently investigated in the area of nanomedicine. Gold nanoparticles have found themselves useful for diagnostic and drug delivery applications. Herein we have reported a novel method for synthesis of gold nanoparticles using a natural, biocompatible and biodegradable polymer; chitosan. Use of chitosan serves dual purpose by acting as a reducing agent in the synthesis of gold nanoparticles and also promotes the penetration and uptake of peptide hormone insulin across the mucosa. To demonstrate the use of chitosan reduced gold nanoparticles as carriers for drug delivery, we report herein the transmucosal delivery of insulin loaded gold nanoparticles.


METHODS
Gold nanoparticles were prepared using different concentrations of chitosan (from 0.01% w/v up to 1% w/v). The gold nanoparticles were characterized for surface plasmon band, zeta potential, surface morphology, in vitro diffusion studies and fluorescence spectroscopy. The in vivo studies in diabetic male Wistar rats were carried out using insulin loaded chitosan reduced gold nanoparticles.


RESULTS
Varying concentrations of chitosan used for the synthesis of gold nanoparticles demonstrated that the nanoparticles obtained at higher chitosan concentrations (>0.1% w/v) were stable showing no signs of aggregation. The nanoparticles also showed long term stability in terms of aggregation for about 6 months. Insulin loading of 53% was obtained and found to be stable after loading. Blood glucose lowering at the end of 2 h following administration of insulin loaded gold nanoparticles to diabetic rats was found to be 30.41 and 20.27% for oral (50 IU/kg) and nasal (10 IU/kg), respectively. Serum gold level studies have demonstrated significant improvement in the uptake of chitosan reduced gold nanoparticles.


CONCLUSIONS
The synthesis of gold nanoparticles using a biocompatible polymer, chitosan would improve its surface properties for binding of biomolecules. Our studies indicate that oral and nasal administration of insulin loaded chitosan reduced gold nanoparticles has led to improved pharmacodynamic activity. Thus, chitosan reduced gold nanoparticles loaded with insulin prove to be promising in controlling the postprandial hyperglycemia.
Bhumkar
Devika R
DR
Department of Pharmaceutics, Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, 411 038, India.
Joshi
Hrushikesh M
HM
Sastry
Murali
M
Pokharkar
Varsha B
VB
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D048271:Chitosan / Q000737:chemistry*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy; D004058:Diffusion; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D006046:Gold / Q000097:blood / Q000737:chemistry*; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000627:therapeutic use; D008297:Male; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009297:Nasal Mucosa / Q000378:metabolism; D010084:Oxidation-Reduction; D010316:Particle Size; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D055672:Static Electricity; D014783:Viscosity
D001786:Blood Glucose; D004337:Drug Carriers; D007328:Insulin; D006046:Gold; D048271:Chitosan