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Jain K.,Pharmaceutical Nanotechnology Research Laboratory | Jain N.K.,Pharmaceutical Nanotechnology Research Laboratory
Journal of Immunological Methods | Year: 2015

Visceral leishmaniasis, which is also known as Kala-Azar, is one of the most severely neglected tropical diseases recognized by the World Health Organization (WHO). The threat of this debilitating disease continues due to unavailability of promising drug therapy or human vaccine. An extensive research is undergoing to develop a promising vaccine to prevent this devastating disease. In this review we compiled the findings of recent research with a view to facilitate knowledge on experimental vaccinology for visceral leishmaniasis. Various killed or attenuated parasite based first generation vaccines, second generation vaccines based on antigenic protein or recombinant protein, and third generation vaccines derived from antigen-encoding DNA plasmids including heterologous prime-boost Leishmania vaccine have been examined for control and prevention of visceral leishmaniasis. Vaccines based on recombinant protein and antigen-encoding DNA plasmids have given promising results and few vaccines including Leishmune®, Leishtec, and CaniLeish® have been licensed for canine visceral leishmaniasis. A systematic investigation of these vaccine candidates can lead to development of promising vaccine for human visceral leishmaniasis, most probably in the near future. © 2015 Elsevier B.V.

Jain K.,Dr Hari Singh Gour University | Jain K.,Pharmaceutical Nanotechnology Research Laboratory | Verma A.K.,CSIR - Central Electrochemical Research Institute | Mishra P.R.,CSIR - Central Electrochemical Research Institute | And 2 more authors.
Nanomedicine: Nanotechnology, Biology, and Medicine | Year: 2015

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. © 2015 Elsevier Inc.

Mehra N.K.,Dr Hari Singh Gour University | Mehra N.K.,Pharmaceutical Nanotechnology Research Laboratory | Jain N.K.,Dr Hari Singh Gour University | Jain N.K.,Pharmaceutical Nanotechnology Research Laboratory
Colloids and Surfaces B: Biointerfaces | Year: 2015

Our main aim in the present investigation was to investigate the cancer targeting potential of docetaxel (DTX) loaded, folic acid (FA) terminated, poly (ethylene glycol) (PEG) conjugated, surface engineered multi walled carbon nanotubes (DTX/FA-PEG-MWCNTs) in tumor bearing Balb/c mice. The percent loading efficiency of DTX/FA-PEG-MWCNTs and DTX loaded MWCNTS (DTX/MWCNTs) was calculated to be 93.40 ± 3.82% and 76.30 ± 2.62%, respectively. Flow cytometry analysis suggested that the DTX/FA-PEG-MWCNTs arrested MCF-7 cells' cycle in the G2 phase and was more cytotoxic as compared to DTX/MWCNTs as well as free drug solution. The obtained pharmacokinetic parameters clearly describe the biocompatibility of engineered nanotubes to degree of functionalization and ability for prolonged residence inside the body. DTX/FA-PEG-MWCNTs was found to be significantly more efficient in tumor suppression as compared with plain MWCNTs (non-targeted) as well as drug solution owing to the enhanced drug release from endosomes after internalization. The DTX/FA-PEG-MWCNTs showed highly significant prolonged survival span (40 days) as compared to DTX/MWCNTs (24 days), free DTX (19 days) and control group (12 days). Overall, we can conclude that the DTX/FA-PEG-MWCNTs shows higher cancer targeting propensity vis a vis minimal side effects in tumor bearing Balb/c mice. © 2015 Elsevier B.V.

Kaur A.,Pharmaceutical Nanotechnology Research Laboratory | Jain K.,Pharmaceutical Nanotechnology Research Laboratory | Jain K.,National Institute of Pharmaceutical Education and Research | Mehra N.K.,Pharmaceutical Nanotechnology Research Laboratory | And 3 more authors.
Artificial Cells, Nanomedicine and Biotechnology | Year: 2016

In this study, we reported folate-conjugated polypropylene imine dendrimers (FA–PPI) as efficient carrier for model anticancer drug, methotrexate (MTX), for pH-sensitive drug release, selective targeting to cancer cells, and anticancer activity. In the in vitro drug release studies this nanoconjugate of MTX showed initial rapid release followed by gradual slow release, and the drug release was found to be pH sensitive with greater release at acidic pH. The ex vivo investigations with human breast cancer cell lines, MCF-7, showed enhanced cytotoxicity of MTX–FA–PPI with significantly enhanced intracellular uptake. The biofate of nanoconjugate was determined in Wistar rat where MTX–FA–PPI showed 37.79-fold increase in the concentration of MTX in liver after 24 h in comparison with free MTX formulation. © 2016 Informa UK Limited, trading as Taylor & Francis Group

Kaur D.,Pharmaceutical Nanotechnology Research Laboratory | Jain K.,Pharmaceutical Nanotechnology Research Laboratory | Jain K.,National Institute of Pharmaceutical Education and Research | Mehra N.K.,Pharmaceutical Nanotechnology Research Laboratory | And 4 more authors.
Journal of Nanoparticle Research | Year: 2016

Dendrimers are hyperbranched, monodispersed macromolecules with multivalent functional end groups. Dendrimers have been explored as carrier for many drugs like anticancer, antiviral, antimalarial, antiprotozoal, anti tubercular drugs. Although a number of different types of dendrimers containing different core molecules, branching monomers and surface functional groups have been designed till date for drug delivery applications, yet the poly(propyleneimine) (PPI) and poly(amidoamine) (PAMAM) dendrimers have been the most explored dendrimers in this regard. In this review, we have summarized a comparative data on PPI and PAMAM dendrimers particularly relevant to their properties, synthesis, toxicity, biomedical applications and drug delivery attributes. © 2016, Springer Science+Business Media Dordrecht.

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