Drug targeting to macrophages using paromomycin-loaded albumin microspheres for treatment of visceral leishmaniasis: an in vitro evaluation

Abstract

Background: Leishmania parasite is an obligate intracellular parasite of the mammalian host and lives inside resident macrophages of liver and spleen. A high dose of paromomycin (PM) is required for the treatment.

Purpose: Preparation and in vitro evaluation of PM loaded albumin microspheres (MS) (of size ≤ 5 µm) to target macrophages for treatment of visceral leishmaniasis.

Methods: PM loaded MS were prepared by spray-drying method using albumin as a polymer matrix and stabilized using heat treatment. These MS were evaluated for product yield, encapsulation efficiency, particle size, size distribution, contact angle, drug–polymer interactions, and for in vitro drug release. Fluorescent labeling and in vitro uptake of these MS was assessed in RAW 264.7 cell line.

Results: PM loaded albumin MS were prepared with a mean particle size ≈3 µm. Free albumin content and contact angle study confirmed the stabilization of these MS. Release studies showed biphasic release pattern. Interaction studies ruled out any possibility of drug–polymer interaction. Uptake study in macrophage confirmed the suitability of prepared MS for macrophage targeting.

Conclusion: The proposed drug-delivery system was found suitable for targeting macrophages in vitro and may serve as an optimum carrier to target macrophages where Leishmania parasite resides.

Keywords::

• Paromomycin
• spray-drying
• albumin microspheres
• thermal stabilization
• parenteral delivery

Acknowledgements

W.K. is thankful to Director, NIPER for the award of SRF. Authors are also thankful to NIPER for funding support to carry out the research work.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.