Therapeutic efficacy of artemisinin-loaded nanoparticles in experimental visceral leishmaniasis.
Visceral leishmaniasis (VL) is a fatal vector-borne parasitic syndrome attributable to the protozoa of the Leishmania donovani complex. The available chemotherapeutic options are not ideal due to their potential toxicity, high cost and prolonged treatment schedule. In the present study, we conjectured the use of nano drug delivery systems for plant-derived secondary metabolite; artemisinin as an alternative strategy for the treatment of experimental VL. Artemisinin-loaded poly lactic co-glycolic acid (ALPLGA) nanoparticles prepared were spherical in shape with a particle size of 220.0±15.0 nm, 29.2±2.0% drug loading and 69.0±3.3% encapsulation efficiency. ALPLGA nanoparticles administered at doses of 10 and 20mg/kg body weight showed superior antileishmanial efficacy compared with free artemisinin in BALB/c model of VL. There was a significant reduction in hepatosplenomegaly as well as in parasite load in the liver (85.0±5.4%) and spleen (82.0±2.4%) with ALPLGA nanoparticles treatment at 20mg/kg body weight compared to free artemisinin (70.3±0.6% in liver and 62.7±3.7% in spleen). In addition, ALPLGA nanoparticle treatment restored the defective host immune response in mice with established VL infection. The protection was associated with a Th1-biased immune response as evident from a positive delayed-type hypersensitivity reaction, escalated IgG2a levels, augmented lymphoproliferation and enhancement in proinflammatory cytokines (IFN-γ and IL-2) with significant suppression of Th2 cytokines (IL-10 and IL-4) after in vitro recall, compared to infected control and free artemisinin treatment. In conclusion, our results advocate superior efficacy of ALPLGA nanoparticles over free artemisinin, which was coupled with restoration of suppressed cell-mediated immunity in animal models of VL.
Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Muzamil Yaqub
MY
Want
Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Mohammad
M
Islamuddin
Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Garima
G
Chouhan
Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, P.O. Box 344, Universities Road, Medina 30001, Saudi Arabia.
Hani A
HA
Ozbak
Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, P.O. Box 344, Universities Road, Medina 30001, Saudi Arabia.
Hassan A
HA
Hemeg
Department of Biophysics and Biochemistry, Ballygunge Science College, University of Calcutta, Kolkata 700019, India.
Anjan Kumar
AK
Dasgupta
Department of Chemistry, University of Kalyani, West Bengal 741235, India.
Asoke Prasun
AP
Chattopadhyay
Parasite Immunology Laboratory, Department of Biotechnology, Jamia Hamdard (Hamdard University), New Delhi 110062, India; Department of Medical Laboratories Technology, Faculty of Applied Medical Sciences, Taibah University, P.O. Box 344, Universities Road, Medina 30001, Saudi Arabia. Electronic address: afrin_farhat@yahoo.co.in.
Farhat
F
Afrin
D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000913:Antibodies, Protozoan / Q000097:blood; D019306:Artemisia / Q000737:chemistry; D037621:Artemisinins / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D018122:B7-1 Antigen / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D007893:Leishmania donovani / Q000187:drug effects* / Q000502:physiology; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008099:Liver / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D013154:Spleen / Q000187:drug effects / Q000469:parasitology / Q000473:pathology; D016896:Treatment Outcome
D000890:Anti-Infective Agents; D000913:Antibodies, Protozoan; D037621:Artemisinins; D018122:B7-1 Antigen; D016207:Cytokines; C031327:artemisinin
Antileishmanial; Drug delivery; Leishmania donovani; Nanoparticles; Visceral leishmaniasis