FOLATE ANCHORED CONJUGATES OF POLY (AMIDOAMINE) (PAMAM) DENDRIMER FOR CONTROLLED SITE SPECIFIC DELIVERY OF PIROXICAM IN ARTHRITIC RATS

The purpose of the present study was to synthesize and evaluate the potential of folate-G.4.0-PAMAM dendrimer conjugates as acceptable vehicle for site specific delivery of piroxicam (PXM) to inflammatory regions and to determine its targeting efficiency in carreganan induced arthritic rats. PXM was selected as a model acidic anti inflammatory drug.  Folic acid was linked to the surface amino groups of G4.0-PAMAM dendrimer through a carbodiimide reaction and loaded with PXM. The coupled conjugates were characterized by ¹H-NMR, IR spectroscopy and polyacrylamide gel electrophoresis (PAGE).  The drug content and % encapsulation efficiency increased with increasing folate content for the dendrimer conjugates. The in- vitro release rate was decreased for the PXM-F1, PXM-F2 and PXM-F3 conjugates when compared with PXM-D1. Drug dendrimer and conjugates were further evaluated for haemolytic toxicity and stability study. There was no change in turbidity, colour, consistency in stability study. Efficacy of plain PXM and dendrimer conjugates was tested by carrageenan induced paw edema model. Pharmacodynamic study revealed 74%, 78%, 85%, 90% inhibition at 4th hour by PXM-F1, PXM-F2 and PXM-F3 conjugates that was maintained above 50% till 12^th hour. This study revealed the supremacy of active targeting over dendrimer mediated passive targeting of an anti-arthritic drug to the inflammatory tissues. The folate-PAMAM dendrimer conjugates are the ideal choice for targeted delivery of antiarthritic drugs to inflammatory regions with reduced side-effects. However, comparison of overall data suggested folate-G-4.0- dendrimer conjugate based formulations to be superior to PXM-D1 as well as pure PXM.