Preparation and characterization of a thioctic acid nanostructured lipid carrier to enhance the absorption profile and limit the nephrotoxicity associated with allopurinol in the treatment of gout

Abstract

Allopurinol (ALP) is the most extensively used drug for lowering blood urate concentrations and thereby decreasing the number of repeated attacks of gout. Despite being a potent drug, ALP suffers from poor oral bioavailability and dose-related nephrotoxicity. Therefore, the current study was designed with the objectives to improve the drug's pharmacokinetics and enhance its renal clearance. For this purpose, a renal protective agent, i.e., thioctic acid (THA), was coadministered with ALP through the optimized ALP-THA-loaded nanostructured lipid carrier (ALP-THA NLC). A face-centered central composite experimental design was implemented for the development of an optimized NLC. Fabricated ALP-THA NLCs were characterized according to particle size and entrapment efficiency. The optimized NLC had a particle size of 70 nm and a percentage of entrapment of 94%. After 12 h of in vitro release study, 74% of the drug was released from NLC, whereas 66% and 60% of the drug was released from the aqueous suspension and tablet, respectively. In addition, the cumulative amount of ALP permeated the intestinal barrier from the optimized NLC, aqueous suspension, and tablet was 1850 ± 211 μg/cm2, 910 ± 350 μg/cm2, and 760 ± 406 μg/cm2, respectively. Hence, the in vitro release and ex vivo permeation study demonstrated more favorable outcomes for the optimized ALP-THA NLC than aqueous suspension or commercially available tablets containing ALP. The in vivo nephrotoxicity study showed that the THA present in ALP-THA NLC restored normal renal function and eliminated the nephrotoxicity associated with ALP. Thus, it can be concluded that a novel optimized ALP-THA NLC could be a vernal scaffold for treating gout.