Amphotericin B-loaded nanoparticles for local treatment of cutaneous leishmaniasis

Drug Deliv Transl Res. 2019 Feb;9(1):76-84. doi: 10.1007/s13346-018-00603-0.

Abstract

Cutaneous leishmaniasis (CL) is an infectious, parasitic disease caused by the protozoan Leishmania. Amphotericin B (AMB) is a macrolide polyene antibiotic presenting potent antifungal and antileishmanial activity, but due to poor water solubility at physiological pH, side effects, and toxicity, its therapeutic efficiency is limited. In the present study, poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with AMB were generated to reduce drug toxicity and facilitate localized delivery over a prolonged time. AMB NPs were characterized for particle size, zeta potential, polydispersity index, and degree of aggregation. In vitro assessments demonstrated its sustained activity against Leishmania major promastigotes and parasite-infected macrophages. A single intralesional administration to infected BALB/c mice revealed that AMB NPs were more effective than AMB deoxycholate in terms of reducing lesion area. Taken together, these findings suggest that AMB NPs improve AMB delivery and can be used for local treatment of CL.

Keywords: Amphotericin B; Cutaneous leishmaniasis; Nanoparticles; Sustained release; Topical therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Amphotericin B / administration & dosage*
  • Amphotericin B / chemistry
  • Amphotericin B / pharmacology
  • Animals
  • Antiprotozoal Agents / administration & dosage*
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology
  • Disease Models, Animal
  • Drug Carriers / chemistry
  • Humans
  • Leishmania major / drug effects*
  • Leishmaniasis, Cutaneous / drug therapy*
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles
  • Particle Size
  • Polyesters / chemistry*
  • Polyglycolic Acid / chemistry*
  • THP-1 Cells

Substances

  • Antiprotozoal Agents
  • Drug Carriers
  • Polyesters
  • Polyglycolic Acid
  • poly(lactide)
  • Amphotericin B