ABSTRACT
The present study was aimed to assess the improvement of existing treatment regimens of Amphotericin B nanoconstrcuts which synergises with alginate for immunostimulation against visceral leishmaniasis. The particle size of Lip-nano (Plain AmB nanoconstructs) and Alg-Lip-nano (alginate capped Lip-nano) was 108.3 +/- 4.3 and 134.2 +/- 5.1 while zeta potential was (+) 28.4 +/- 3.3 and (-) 19.8 +/- 2.1 respectively. Percentage of parasite inhibition (intramacrophagic amastigotes) at 0.1 microg/ml conc. of AmB in case of Alg-Lip-nano (58%) was significantly higher (P = 0.05) compared to Lip-nano (48%). This supports that alginate coating over particles can activate macrophages to synergistically act with AmB in effective killing of parasite. This observation generates interest that immunotherapy with chemotherapeutic activity of AmB can effectively increase cure rate in visceral leishmaniasis.
Subject(s)
Alginates/chemistry , Amphotericin B/administration & dosage , Leishmania/drug effects , Leishmania/physiology , Lipids/chemistry , Nanocapsules/chemistry , Amphotericin B/chemistry , Antiprotozoal Agents/administration & dosage , Antiprotozoal Agents/chemistry , Cell Survival/drug effects , Glucuronic Acid/chemistry , Hexuronic Acids/chemistry , Nanocapsules/administration & dosage , Treatment OutcomeABSTRACT
This study was aimed to develop chitosan coupled lipid nanoparticle (Ch-Ptx-Lip), where immunomodulatory activity of chitosan and chemotherapeutic effect of paclitaxel can synergistically enhance efficacy of this novel drug delivery system. Particle size, zeta potential and % Entrapment Efficiency (%EE) of Ch-Ptx-Lip was found to be 113.3 +/- 4.5 nm (PDI: 0.38), (+)35.7 +/- 2.9 mV and 96.4 +/- 1.8% respectively. Morphological evaluation of these particles by TEM shows circular bilayer structure along with outer polymer layers. Ch-Ptx-Lip showed significantly enhanced cytotoxicity (p < 0.05) compared with marketed formulation (Ptx Solution) and Ptx-Lip when evaluated in-vitro by MTT assay on MCF-7 cell lines. Improved efficacy with lower dose of drug can be a new strategy against cancer with minimum side effects and shorter treatment duration.
Subject(s)
Breast Neoplasms/drug therapy , Chitosan/chemistry , Lipids/chemistry , Nanocapsules/chemistry , Paclitaxel/administration & dosage , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Breast Neoplasms/pathology , Cell Line, Tumor , Cell Survival/drug effects , Humans , Nanocapsules/administration & dosage , Paclitaxel/chemistry , Treatment OutcomeABSTRACT
The present study was aimed to assess the efficacy of developed transfersome (TF-3) formulation bearing amphotericin B (AmB) against sensitive and resistant clinical isolates of L donovani and compared with conventional liposomal formulation (F-2) and free AmB (F-1). The skin permeation of AmB from TF-3 was performed using Franz diffusion cell using rat skin which showed fickian diffusion across the skin. When tested against L. donovani (intramacrophagic amastigotes), it has been observed that TF was more effective than F-1 and F-2 formulation in sensitive and resistant clinical isolates. The data provides evidences that the TF formulation owing to its fluidized behaviour imparted by sodium deoxycholate, enables to penetrate well in the infected cells and thus provide enhanced activity. The permeation study also supports this data as the flux value of AmB through TF formulation was 1.5 fold higher compared to conventional liposomes suggesting improved penetration and better partitioning in skin layers. Implicit to this preliminary data it is evident that the AmB loaded TF formulation has potential as alternate chemotherapeutic approach to control of VL. Potential utilities of novel formulation as a transdermal delivery of AmB for leishmaniasis necessitates further elaborated investigations which is underway in our laboratory.
