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Surface-Modified Liposomal Formulation of Amphotericin B: In vitro Evaluation of Potential Against Visceral Leishmaniasis

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Abstract

Surface modification of liposomes with targeting ligands is known to improve the efficacy with reduced untoward effects in treating infective diseases like visceral leishmaniasis (VL). In the present study, modified ligand (ML), designed by modifying polysaccharide with a long chain lipid was incorporated in liposomes with the objective to target amphotericin B (Amp B) to reticuloendothelial system and macrophages. Conventional liposomes (CL) and surface modified liposomes (SML) were characterized for size, shape, and entrapment efficiency (E.E.). Amp B SML with 3% w/w of ML retained the vesicular nature with particle size of ∼205 nm, E.E. of ∼95% and good stability. SML showed increased cellular uptake in RAW 264.7 cells which could be attributed to receptor-mediated endocytosis. Compared to Amp B solution, Amp B liposomes exhibited tenfold increased safety in vitro in RAW 264.7 and J774A.1 cell lines. Pharmacokinetics and biodistribution studies revealed high t 1/2, area under the curve (AUC)0–24, reduced clearance and prolonged retention in liver and spleen with Amp B SML compared to other formulations. In promastigote and amastigote models, Amp B SML showed enhanced performance with low 50% inhibitory concentration (IC50) compared to Amp B solution and Amp B CL. Thus, due to the targeting ability of ML, SML has the potential to achieve enhanced efficacy in treating VL.

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Acknowledgments

The work was supported by the fellowship grant from University Grant Commission, Delhi, India. The authors would also like to thank Jaslok Hospital, Mumbai, India, for TEM analysis of samples.

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Authors and Affiliations

  1. Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India

    Shilpa N. Patere, Pankaj O. Pathak & Mangal S. Nagarsenker

  2. Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, 781039, India

    Anil Kumar Shukla, Rajesh Kumar Singh & Vikash Kumar Dubey

  3. Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India

    Miten J. Mehta, Anand G. Patil & Vikram Gota

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  1. Shilpa N. Patere
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  2. Pankaj O. Pathak
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Correspondence to Mangal S. Nagarsenker.

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Patere, S.N., Pathak, P.O., Kumar Shukla, A. et al. Surface-Modified Liposomal Formulation of Amphotericin B: In vitro Evaluation of Potential Against Visceral Leishmaniasis. AAPS PharmSciTech 18, 710–720 (2017). https://doi.org/10.1208/s12249-016-0553-8

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  • DOI: https://doi.org/10.1208/s12249-016-0553-8

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