Chondroitin nanocapsules enhanced doxorubicin induced apoptosis against leishmaniasis via Th1 immune response.
Current leishmaniasis treatment is strangled due to concealed residence of parasite and reduced host cell mediated immune response. To circumvent above challenges, novel macrophage targeted oily core polymeric shell based doxorubicin (DOX) loaded nanocapsules (NCAPs) were fabricated employing chondroitin sulphate (CHD) for complimentary immunotherapy coupled chemotherapy against leishmaniasis. Excellent encapsulation efficiency along with pH dependent drug release was demonstrated by NCAPs. Improved cell cycle arrest at G1-S phase (1.56 folds) and apoptosis against promastigotes (6.26 folds), support the remarkable in-vitro antileishmanial activity of NCAPs (IC50: 0.254±0.038 μg/ml) compared to free DOX (IC50: 0.543±0.012 μg/ml). In-vivo antileishmanial activity in hamsters represented a significantly enhanced parasitic inhibition by NCAPs (1.42 folds). Improved activity was mediated via immunotherapeutic activity of NCAPs which up-regulated Th1 immune response (IL-12, INF-γ, and TNF-α) and down-regulated Th2 immune response (IL-4, IL-10, and TGF-β). In conclusion, current novel nano-formulation could be a viable option against leishmaniasis.
Amity Institute of Pharmacy, Amity University, Lucknow, UP 226 028, India. Electronic address: mohinichaurasia@gmail.com.
Mohini
M
Chaurasia
Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, UP 226 031, India.
Vivek K
VK
Pawar
Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, UP 226 031, India.
Anil K
AK
Jaiswal
Parasitology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, UP 226 031, India.
Anuradha
A
Dube
Department of Pharmaceutical Sciences, Banasthali VidyaPeeth, Banasthali, Rajasthan 304 022, India.
Sarvesh K
SK
Paliwal
Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, UP 226 031, India.
Manish K
MK
Chourasia
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002807:Chondroitin / Q000737:chemistry*; D003412:Cricetulus; D004317:Doxorubicin / Q000494:pharmacology*; D004339:Drug Compounding; D065546:Drug Liberation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D007111:Immunity, Cellular / Q000187:drug effects*; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D018664:Interleukin-12 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000276:immunology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D053769:Nanocapsules; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D058408:Th1-Th2 Balance / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000469:parasitology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
D000981:Antiprotozoal Agents; D053769:Nanocapsules; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D004317:Doxorubicin; D007371:Interferon-gamma; D002807:Chondroitin
Apoptosis; Cell cycle arrest; Chondroitin sulphate; Cytokine; Doxorubicin