Nano-elastic liposomes as multidrug carrier of sodium stibogluconate and ketoconazole: A potential new approach for the topical treatment of cutaneous Leishmaniasis

Eur J Pharm Sci. 2020 Mar 30:145:105256. doi: 10.1016/j.ejps.2020.105256. Epub 2020 Feb 4.

Abstract

The present study evaluates the efficacy of sodium stibogluconate (SSG) co-loaded with ketoconazole (KTZ) in nano-elastic liposomes (NELs) for the topical treatment of cutaneous leishmaniasis (CL). SSG-KTZ co-loaded NELs were developed and assessed for various physicochemical properties and anti-leishmanial potential. The optimized nano-vesicles have an average size of 212.8 ± 3.1 nm and entrapment efficiency of 61.2 ± 2.9%. SSG-KTZ co-loaded NELs displayed 5.37-fold higher skin permeation of SSG as compared to drug solution. SSG and KTZ displayed a synergistic interaction and flow cytometry revealed enhanced killing of DsRed Leishmania mexicana in infected macrophages. In-vitro and in-vivo anti-leishmanial studies indicated a 10.67-fold lower IC50 value and a 35.33-fold reduced parasitic burden as compared with plain SSG solution, respectively. SSG-KTZ co-loaded NELs were found to be a promising approach for the topical treatment of CL.

MeSH terms

  • Administration, Topical
  • Animals
  • Antimony Sodium Gluconate / administration & dosage*
  • Antimony Sodium Gluconate / metabolism
  • Antiprotozoal Agents / administration & dosage*
  • Antiprotozoal Agents / metabolism
  • Drug Carriers / administration & dosage
  • Drug Carriers / metabolism
  • Elasticity*
  • Female
  • Ketoconazole / administration & dosage*
  • Ketoconazole / metabolism
  • Leishmaniasis, Cutaneous / drug therapy*
  • Leishmaniasis, Cutaneous / metabolism
  • Liposomes
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles / administration & dosage*
  • Nanoparticles / metabolism
  • Organ Culture Techniques
  • Random Allocation
  • Skin / drug effects
  • Skin / metabolism

Substances

  • Antiprotozoal Agents
  • Drug Carriers
  • Liposomes
  • Ketoconazole
  • Antimony Sodium Gluconate