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The main objective of the study was to investigate the efficacy of chitosan to facilitate brain bioavailability of intranasally administered nerve growth factor (NGF). In vitro permeability studies and electrical resistance studies were carried out across the bovine olfactory epithelium using Franz diffusion cells. The bioavailability of intranasally administered NGF in rat hippocampus was determined by carrying out brain microdialysis in Sprague Dawley rats. The in vitro permeation flux across the olfactory epithelium of NGF solution without chitosan (control) was found to be 0.37 ± 0.06 ng/cm 2 /h. In presence of increasing concentration of chitosan (0.1%, 0.25% and 0.5% w/v) the permeation flux of NGF was found to be 2.01 ± 0.12, 3.88 ± 0.19 and 4.12 ± 0.21 ng/cm 2 /h respectively. Trans-olfactory epithelial electrical resistance decreased ~34.50 ± 4.06 % in presence of 0.25 % w/v chitosan. The C max in rats administered with 0.25 % w/v chitosan and NGF was 1008.62 ± 130.02 pg/ml which was significantly higher than that for rats administered with NGF only 97.38 ± 10.66 pg/ml. There was ~14 fold increase in the bioavailability of intranasally administered NGF with chitosan than without chitosan. Chitosan can enhance the brain bioavailability of intranasally administered NGF.

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The efficiency of low voltage electropulsation (LVE) technique for delivery of drugs and macromolecules across the skin was investigated. The in vitro studies were carried out across the porcine epidermis in Franz diffusion cells using salicylic acid and fluorescein labeled Dextran of molecular weight 10,000 Da (FD10K). LVE enhanced the transport of salicylic acid and FD10K by approximately 4-fold and approximately 2-fold, respectively over the control. The potential application of LVE in transdermal drug delivery was studied in the case of lidocaine hydrochloride. The transport of lidocaine hydrochloride was enhanced by approximately 8-fold over the control. The transport enhancement by LVE was compared with that of 1 min and 20 min constant DC iontophoresis at 0.5 mA/cm(2). Iontophoresis applied for 1 min delivers equivalent electrical dose as that of LVE (50 ms pulses for 20 min at 1 Hz) in the current set up. The transport by application of iontophoresis for 1 min was significantly less than the control (passive diffusion for 20 min). However, the application of iontophoresis for 20 min (electrical dose approximately 20-fold more than that of LVE) resulted in comparable drug transport as that of LVE. It is evident from the results of this experiment that the transdermal delivery of drugs could be enhanced by LVE which is a rather mild technique than electroporation or iontophoresis.

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