Gold nanoparticles as a potential carrier for transmucosal vaccine delivery.

The transmucosal administration of vaccines leads to development of systemic as well as local immune response. However, development of delivery systems targeted at these immunologically active sites remains a practical challenge. The objective of the present study was to explore the potential of chitosan reduced gold nanoparticles (AuNps) for the transmucosal delivery of tetanus toxoid vaccine. Two different nanoparticulate systems were developed utilizing chitosan. Tetanus toxoid was loaded on chitosan nanoparticles and chitosan reduced AuNps. The current study clearly demonstrated that subcutaneous TT administration lead to generation of systemic response, but did not elicit any mucosal response. However TT loaded AuNps were able to generate a significantly higher mucosal response following oral administration. In conclusion, a novel approach utilizing chitosan reduced gold nanoparticles for the development of transmucosal vaccine formulation was successfully demonstrated.

Acute and subacute toxicity studies of chitosan reduced gold nanoparticles: a novel carrier for therapeutic agents.

The objective of the present study was to evaluate the oral toxicity of chitosan reduced gold nanoparticles so as to demonstrate its applicability for drug delivery application. Acute oral toxicity studies in female rats documented no deaths or treatment related complications. The LD50 value of gold nanoparticles was found to be greater than 2000 mg/kg. In case of sub-acute oral toxicity studies, gold nanoparticles were administered orally to male and female rats for a period of 28-days. At the end of study blood samples were collected for haematology and biochemical analysis. For histopathological analysis, organs of animals were weighed and processed for examination. All animals survived the duration of the study, with no significant changes in clinical signs, body weight, food consumption, hematological parameters, organ weights and histopathological findings. These studies establish that chitosan reduced gold nanoparticles produced no treatment related toxicity in rats following oral administration, thus can be exploited for potential therapeutic applications.

Chitosan reduced gold nanoparticles as novel carriers for transmucosal delivery of insulin.

PURPOSE: 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. MATERIALS AND 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.

Gold nanoparticles as carriers for efficient transmucosal insulin delivery.

Nanomaterials have gained tremendous importance in biology and medicine because they can be used as carriers for delivering small molecules such as drugs, proteins, and genes. We report herein the binding of the hormone insulin to gold nanoparticles and its application in transmucosal delivery for the therapeutic treatment of diabetes mellitus. Insulin was loaded onto bare gold nanoparticles and aspartic acid-capped gold nanoparticles and delivered in diabetic Wistar rats by both oral and intranasal (transmucosal) routes. Our principle observations are that there is a significant reduction of blood glucose levels (postprandial hyperglycemia) when insulin is delivered using gold nanoparticles as carriers by the transmucosal route in diabetic rats. Furthermore, control of postprandial hyperglycemia by the intranasal delivery protocol is comparable to that achieved using the standard subcutaneous administration used for type I diabetes mellitus, thus showing considerable promise for further development.