Magnetophoresis is a method of enhancement of drug permeation across the biological barriers by application of magnetic field. The present study investigated the mechanistic aspects of magnetophoretic transdermal drug delivery and also assessed the feasibility of designing a magnetophoretic transdermal patch system for the delivery of lidocaine. In vitro drug permeation studies were carried out across the porcine epidermis at different magnetic field strengths. The magnetophoretic drug permeation “flux enhancement factor” was found to increase with the applied magnetic field strength. The mechanistic studies revealed that the magnetic field applied in this study did not modulate permeability of the stratum corneum barrier. The predominant mechanism responsible for magnetically mediated drug permeation enhancement was found to be “magnetokinesis”. The octanol/water partition coefficient of drugs was also found to increase when exposed to the magnetic field. A reservoir type transdermal patch system with a magnetic backing was designed for in vivo studies. The dermal bioavailability (AUC0–6 h) from the magnetophoretic patch system in vivo, in rats was significantly higher than the similarly designed nonmagnetic control patch.
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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