title: Characterization and evaluation of amphotericin B loaded MDP conjugated poly(propylene imine) dendrimers.
abstract: This paper describes a novel strategy for targeted delivery of amphotericin B (AmB) to macrophages with muramyl dipeptide (MDP) conjugated multimeric poly(propyleneimine) (PPI) dendrimers. Synergistic antiparasitic activity due to immunostimulation by multimeric presentation of MDP on dendrimers was anticipated. MDP conjugated 5.0G PPI (MdPPI) dendrimers were synthesized and characterized. Therapeutic activity and toxicity of dendrimeric formulation of AmB (MdPPIA) were compared with marketed formulations of AmB. Highly significant (P<0.01) reduction in toxicity was observed in hemolytic toxicity and cytotoxicity studies in erythrocytes and J774A.1 macrophage cells, respectively. Formulation MdPPIA showed appreciable macrophage targeting potential and higher or equivalent antiparasitic activity against parasite infected macrophage cell lines and in vivo infection in Balb/c mice. These results suggest the developed MDP conjugated dendrimeric formulation of AmB as a promising immunostimulant targeted drug delivery system and a safer alternative to marketed formulations. From the clinical editor: Parasitic infections remain a significant issue in the clinical setting. The authors in this article studied the use of ligand anchored dendrimeric formulation of Amphotericin B to target infected macrophages and showed reduced toxicity, high anti-leishmanial activity. This may add another treatment option to available formulations in the future.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, India; Pharmaceutical Nanotechnology Research Laboratory, ISF College of Pharmacy, Moga, India.
authors.forename: Keerti
authors.initials: K
authors.lastname: Jain
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India.
authors.forename: Ashwni Kumar
authors.initials: AK
authors.lastname: Verma
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India.
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, India; Pharmaceutical Nanotechnology Research Laboratory, ISF College of Pharmacy, Moga, India. Electronic address: keertijain02@gmail.com.
authors.forename: Narendra Kumar
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000666:Amphotericin B / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D050091:Dendrimers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011126:Polypropylenes / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D050091:Dendrimers; D004337:Drug Carriers; D011126:Polypropylenes; C443641:poly(propyleneimine); D000119:Acetylmuramyl-Alanyl-Isoglutamine; D000666:Amphotericin B
keywords: Amphotericin B; Dendrimers; Immunostimulation; MDP; Macrophage