title: Surface-Modified Liposomal Formulation of Amphotericin B: In vitro Evaluation of Potential Against Visceral Leishmaniasis.
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 t1/2, 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.
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
authors.forename: Shilpa N
authors.initials: SN
authors.lastname: Patere
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India.
authors.forename: Pankaj O
authors.initials: PO
authors.lastname: Pathak
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, 781039, India.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar Shukla
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, 781039, India.
authors.forename: Rajesh Kumar
authors.initials: RK
authors.lastname: Singh
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, 781039, India.
authors.forename: Vikash
authors.initials: V
authors.lastname: Kumar Dubey
authors.affiliation: Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India.
authors.forename: Miten J
authors.initials: MJ
authors.lastname: Mehta
authors.affiliation: Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India.
authors.forename: Anand G
authors.initials: AG
authors.lastname: Patil
authors.affiliation: Advanced Centre for Treatment, Research & Education in Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai, 410210, India.
authors.forename: Vikram
authors.initials: V
authors.lastname: Gota
authors.affiliation: Department of Pharmaceutics, Bombay College of Pharmacy, Kalina, Santacruz (E), Mumbai, 400098, India. mangal.nagarsenker@gmail.com.
authors.forename: Mangal S
authors.initials: MS
authors.lastname: Nagarsenker
mesh_terms: D000666:Amphotericin B / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008081:Liposomes / Q000737:chemistry*; D008099:Liver / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D051379:Mice; D010316:Particle Size; D013154:Spleen / Q000469:parasitology; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; C068538:liposomal amphotericin B; D000666:Amphotericin B
keywords: amphotericin B; biodistribution; leishmaniasis; liposomes; pharmacokinetics