Urate crystal degradation for treatment of gout: a nanoparticulate combination therapy approach.

Abstract

The objective of the present work was to develop polymeric nanoparticles of uricase and aceclofenac (NSAID) and to incorporate them into gel, for delivering drugs to synovial joints, for effective treatment of Gout. Nanoparticles containing uricase and aceclofenac were prepared by double emulsion solvent evaporation method and emulsion solvent evaporation, using PLGA (50:50) as carrier, respectively. Process parameters were optimized using Taguchi L4 orthogonal array and L9 array, respectively. The formulations were characterized for particle size, entrapment efficiency, surface charge, in vitro drug release, ex vivo drug permeation, and urate crystal degradation activity. The particle size and entrapment efficiency for optimized batch was found to be 228.8 nm and 81.26% for uricase nanoparticles and 288.5 nm and 85.36% for aceclofenac nanoparticles, respectively. The developed nanoparticles formulations displayed zero order and Higuchi release kinetics with non-Fickian diffusion, respectively. The in vivo studies were performed in rabbit model. Topical application of gel containing polymeric uricase nanoparticles alone and a combination of both, uricase nanoparticles and aceclofenac nanoparticles in rabbit model test groups, provided complete removal of urate crystals and inflammation within 40 and 25 days of treatment, respectively. The combination treatment therapy resulted in effective treatment of gout due to degradation of crystals and anti-inflammatory response.

• Authors: Sanjay Tiwari, Harinath Dwivedi, Koshy M Kymonil, Shubhini A Saraf
• Journal: Drug delivery and translational research (Drug Deliv Transl Res) Vol. 5 Issue 3 Pg. 219-30 (Jun 2015) ISSN: 2190-3948 [Electronic] United States
• PMID: 25787730 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Drug Carriers
• Gout Suppressants
• Diclofenac
• Uric Acid
• Urate Oxidase
• aceclofenac

Topics

• Absorption, Physiological
• Administration, Cutaneous
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Chickens
• Diclofenac (administration & dosage, analogs & derivatives, chemistry, pharmacokinetics, therapeutic use)
• Drug Carriers (administration & dosage, chemistry, therapeutic use)
• Drug Compounding
• Drug Stability
• Drug Therapy, Combination
• Eggs
• Goats
• Gout (drug therapy, immunology, metabolism)
• Gout Suppressants (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• In Vitro Techniques
• Nanoparticles (chemistry)
• Rabbits
• Solubility
• Synovial Fluid (chemistry, enzymology)
• Tissue Distribution
• Urate Oxidase (administration & dosage, chemistry, pharmacokinetics, therapeutic use)
• Uric Acid (antagonists & inhibitors, metabolism)