Immunoadjuvant chemotherapy of visceral leishmaniasis in hamsters using amphotericin B-encapsulated nanoemulsion template-based chitosan nanocapsules.
The accessible treatment options for life-threatening neglected visceral leishmaniasis (VL) disease have problems with efficacy, stability, adverse effects, and cost, making treatment a complex issue. Here we formulated nanometric amphotericin B (AmB)-encapsulated chitosan nanocapsules (CNC-AmB) using a polymer deposition technique mediated by nanoemulsion template fabrication. CNC-AmB exhibited good steric stability in vitro, where the chitosan content was found to be efficient at preventing destabilization in the presence of protein and Ca(2+). A toxicity study on the model cell line J774A and erythrocytes revealed that CNC-AmB was less toxic than commercialized AmB formulations such as Fungizone and AmBisome. The results of in vitro (macrophage-amastigote system; 50% inhibitory concentration [IC(50)], 0.19 ± 0.04 μg AmB/ml) and in vivo (Leishmania donovani-infected hamsters; 86.1% ± 2.08% parasite inhibition) experiments in conjunction with effective internalization by macrophages illustrated the efficacy of CNC-AmB at augmenting antileishmanial properties. Quantitative mRNA analysis by real-time PCR (RT-PCR) showed that the improved effect was synergized with the upregulation of tumor necrosis factor alpha (TNF-α), interleukin-12 (IL-12), and inducible nitric oxide synthase and with the downregulation of transforming growth factor β (TGF-β), IL-10, and IL-4. These research findings suggest that a cost-effective CNC-AmB immunoadjuvant chemotherapeutic delivery system could be a viable alternative to the current high-cost commercial lipid-based formulations.
Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
Shalini
S
Asthana
Anil K
AK
Jaiswal
Pramod K
PK
Gupta
Vivek K
VK
Pawar
Anuradha
A
Dube
Manish K
MK
Chourasia
D000666:Amphotericin B / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D048271:Chitosan / Q000737:chemistry*; D006224:Cricetinae; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D008297:Male; D053769:Nanocapsules / Q000737:chemistry*
D000981:Antiprotozoal Agents; D053769:Nanocapsules; D000666:Amphotericin B; D048271:Chitosan