The present study was designed to improve the oral bioavailability of two clinically important antifungal drugs-clotrimazole and econazole. Each drug was encapsulated in nanoparticles of a synthetic polymer (polylactide-co-glycolide, PLG) or a natural polymer (alginate stabilized with chitosan). The nanoparticles were prepared by the emulsion-solvent-evaporation technique in case of PLG and by the cation-induced controlled gelification in case of alginate. Drug encapsulation efficiency was better (>90%) for the alginate formulation compared with the PLG formulation (nearly 50%). The formulations were orally administered to mice and the drugs were analyzed in plasma by a validated HPLC technique. The biodistribution/pharmacokinetic data suggested that there was a controlled drug release for 5-6 days with each of the formulations, compared with unencapsulated drugs, which were cleared within 3-4 h of oral/intravenous administration. There was a striking improvement in the relative and absolute bioavailability of each drug. Further, the drugs were detected in the tissues (lungs, liver and spleen) till 6-8 days in case of nanoparticles whereas free drugs were cleared by 12 h. Overall, the alginate formulation appeared to be better than the PLG formulation. The results emphasize the power of nanotechnology to make the concept of enhancement in oral bioavailability of azole antifungal drugs come to reality.