Fabrication of 3-O-sn-Phosphatidyl-L-serine Anchored PLGA Nanoparticle Bearing Amphotericin B for Macrophage Targeting

Pharm Res. 2018 Feb 9;35(3):60. doi: 10.1007/s11095-017-2293-1.

Abstract

Purpose: To fabricate, characterize and evaluate 3-O-sn-Phosphatidyl-L-serine (PhoS) anchored PLGA nanoparticles for macrophage targeted therapeutic intervention of VL.

Materials and methods: PLGA-AmpB NPs were prepared by well-established nanoprecipitation method and decorated with Phos by thin film hydration method. Physico-chemical characterization of the formulation was done by Zetasizer nano ZS and atomic force microscopy.

Results: The optimized formulation (particle size, 157.3 ± 4.64 nm; zeta potential, - 42.51 ± 2.11 mV; encapsulation efficiency, ∼98%) showed initial rapid release up to 8 h followed by sustained release until 72 h. PhoS generated 'eat-me' signal driven augmented macrophage uptake, significant increase in in-vitro (with ∼82% parasite inhibition) and in-vivo antileishmanial activity with preferential accumulation in macrophage rich organs liver and spleen were found. Excellent hemo-compatibility justified safety profile of developed formulation in comparison to commercial formulations.

Conclusion: The developed PhoS-PLGA-AmpB NPs have improved efficacy, and necessary stability which promisingly put itself as a better alternative to available commercial formulations for optimized treatment of VL.

Keywords: 3-O-sn-Phosphatidyl-L-serine; amphotericin B; macrophage targeting; visceral leishmaniasis.

MeSH terms

  • Amphotericin B / administration & dosage*
  • Animals
  • Antiprotozoal Agents / administration & dosage*
  • Cell Line
  • Delayed-Action Preparations / administration & dosage
  • Disease Models, Animal
  • Drug Carriers / chemistry*
  • Drug Compounding / methods
  • Drug Evaluation, Preclinical
  • Drug Stability
  • Humans
  • Leishmania donovani / drug effects
  • Leishmaniasis, Visceral / drug therapy*
  • Macrophages / drug effects*
  • Macrophages / parasitology
  • Male
  • Mice
  • Nanoparticles / chemistry
  • Phosphatidylserines / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry
  • Rats
  • Rats, Wistar
  • Treatment Outcome

Substances

  • Antiprotozoal Agents
  • Delayed-Action Preparations
  • Drug Carriers
  • Phosphatidylserines
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Amphotericin B