Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis

Kansal, Shaswat; Tandon, Rajendra; Dwivedi, Pankaj; Misra, Pragya; Verma, Priya Ranjan Prasad; Dube, Anuradha; Mishra, Prabhat Ranjan

doi:10.1093/jac/dks286

Cited by 60 publications

(42 citation statements)

References 55 publications

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“…The low-energy emulsification method was utilized to prepare NE as reported previously (Kansal et al, 2012). In brief, NE was obtained from a mixture of SBO (20 wt %) containing free DOX base and Span 80/Tween 80 (weight ratio of approximately 0.43/0.57) by slowly adding aqueous phase containing PSS (0.025 wt %) at a flow rate of 1 mL·min −1 with gentle agitation using a magnetic stirrer at a temperature of 60°C.…”

Section: Preparation Of Nano-emulsions (Ne)mentioning

confidence: 99%

Coating doxorubicin‐loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1‐type immune responses

Kansal

Tandon

Verma

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThe aim of the present study was to evaluate the immunomodulatory and chemotherapeutic potential of alginate-(SA) coated nanocapsule (NCs) loaded with doxorubicin (SA-NCs-DOX) against visceral leishmaniasis in comparison with nano-emulsions containing doxorubicin (NE-DOX). EXPERIMENTAL APPROACHNE-DOX was prepared using low-energy emulsification methods. Stepwise addition of protamine sulphate and SA in a layer-by-layer manner was used to form SA-NCs-DOX. SA-NCs-DOX, NE-DOX and Free DOX were compared for their cytotoxicity against Leishmania donovani-infected macrophages in vitro and generation of T-cell responses in infected hamsters in vivo. KEY RESULTSSize and ζ potential of the NE-DOX and SA-NCs-DOX formulations were 310 ± 2.1 nm and (−)32.6 ± 2.1 mV, 342 ± 4.1 nm and (−)29.3 ± 1.2 mV respectively. SA-NCs-DOX was better (1.5 times) taken up by J774A.1 macrophages compared with NE-DOX. SA-NCs -DOX showed greater efficacy than NE-DOX against intramacrophagic amastigotes. SA-NCs-DOX treatment exhibited enhanced apoptotic efficiency than NE-DOX and free DOX as evident by cell cycle analysis, decrease in mitochondrial membrane potential, ROS and NO production. T-cell responses, when assessed through lymphoproliferative responses, NO production along with enhanced levels of iNOS, TNF-α, IFN-γ and IL-12 were found to be up-regulated after SA-NCs-DOX, compared with responses to NE-DOX in vivo. Parasitic burden was decreased in Leishmania-infected hamsters treated with SA-NCs-DOX, compared with NE-DOX. CONCLUSIONS AND IMPLICATIONSOur results provide insights into the development of an alternative approach to improved management of leishmaniasis through a combination of chemotherapy with stimulation of the innate immune system.

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Section: Preparation Of Nano-emulsions (Ne)mentioning

confidence: 99%

Coating doxorubicin‐loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1‐type immune responses

Kansal

Tandon

Verma

et al. 2014

British J Pharmacology

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“…PS has been used as targeting legend due to its ability to be recognized by the receptors including CD68, CD14, annexins, b2 glycoprotein I (11), GAS6, and scavenger receptors (12). These receptors can play a vital role in recognition of PS-coated nanoparticles and can effectively target tumor cells of the kidney.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity and Genotoxicity in Human Embryonic Kidney Cells Exposed to Surface Modify Chitosan Nanoparticles Loaded with Curcumin

et al. 2015

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Abstract. The rapid progress in the development and scientific investments of modified nanoparticles are due to their owed activity to various diseased conditions for which they are prepared. But the toxicity which they cause cannot be overlooked. The present study demonstrates the development of phosphatidylserine (PS)-coated chitosan (CS) nanoparticles (NPs) loaded with curcumin (CU), which was then investigated against human embryonic kidney cells (HEK 293) for its cytotoxic and genotoxic effect in rats. The CU-loaded CNPs (CNPs-CU) have been prepared by ionic gelation method, later which were grafted with PS. CNPs-CU and PS-CNPs-CU have been evaluated for their size, poly dispersity index, amount of drug entrapped, and in vitro CU release. CNPs-CU has an average size 167.6 ± 3.53 nm and polydispersity index (PDI) 0.115 ± 0.014, whereas PS-CNPs-CU shows average size 220 ± 3.67 nm and PDI 0.148 ± 0.019. Surface morphology of prepared NPs was confirmed by high-resolution transmission electron microscopy (HR-TEM). There was no major difference in cell viability between PS-CNPs-CU and CNPs-CU when they were exposed to HEK 293 cells at all equivalent concentrations. A series of genotoxic studies were conducted, which revealed the non-genotoxicity potential of the developed complexes. These results demonstrated that PS-CNPs-CU may be useful as potential delivery system.

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“…197 A NE loaded with doxorubicin (NE-DOX) was further grafted with phosphatidylserine (PS) to enhance the cellular uptake. 77 There was significant improvement in activity with PS-NE-DOX on the spleen parasitic burden in Leishmania-infected hamsters, in comparison to uncoated NE or free drug.…”

Section: Nanoemulsions (Nes) and Niosomesmentioning

confidence: 91%

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

Bruni¹,

Stella²,

Giraudo³

et al. 2017

IJN

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Leishmaniasis is a vector-borne zoonotic disease caused by protozoan parasites of the genus Leishmania , which are responsible for numerous clinical manifestations, such as cutaneous, visceral, and mucocutaneous leishmaniasis, depending on the site of infection for particular species. These complexities threaten 350 million people in 98 countries worldwide. Amastigotes living within macrophage phagolysosomes are the principal target of antileishmanial treatment, but these are not an easy target as drugs must overcome major structural barriers. Furthermore, limitations on current therapy are related to efficacy, toxicity, and cost, as well as the length of treatment, which can increase parasitic resistance. Nanotechnology has emerged as an attractive alternative as conventional drugs delivered by nanosized carriers have improved bioavailability and reduced toxicity, together with other characteristics that help to relieve the burden of this disease. The significance of using colloidal carriers loaded with active agents derives from the physiological uptake route of intravenous administered nanosystems (the phagocyte system). Nanosystems are thus able to promote a high drug concentration in intracellular mononuclear phagocyte system (MPS)-infected cells. Moreover, the versatility of nanometric drug delivery systems for the deliberate transport of a range of molecules plays a pivotal role in the design of therapeutic strategies against leishmaniasis. This review discusses studies on nanocarriers that have greatly contributed to improving the efficacy of antileishmaniasis drugs, presenting a critical review and some suggestions for improving drug delivery.

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Development of nanocapsules bearing doxorubicin for macrophage targeting through the phosphatidylserine ligand: a system for intervention in visceral leishmaniasis

Abstract: We conclude that the PS targeting moiety can provide a new insight for efficient drug delivery to specialized macrophages and thus may be developed for effective use in macrophage-specific delivery systems, especially for leishmaniasis.

Cited by 60 publications

References 55 publications

Coating doxorubicin‐loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1‐type immune responses

Coating doxorubicin‐loaded nanocapsules with alginate enhances therapeutic efficacy against Leishmania in hamsters by inducing Th1‐type immune responses

Cytotoxicity and Genotoxicity in Human Embryonic Kidney Cells Exposed to Surface Modify Chitosan Nanoparticles Loaded with Curcumin

Nanostructured delivery systems with improved leishmanicidal activity: a critical review

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