Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania

Tiwari, Rajeshwari ; Banerjee, Saswati ; Tyde, Deepak ; Saha, Krishna Das ; Ethirajan, Anitha ; Mukherjee, Niladri ; Chattopadhy, Samit ; Pramanik, Sumit Kumar ; Das, Amitava (2021) Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania Bioconjugate Chemistry, 32 (2). pp. 245-253. ISSN 1043-1802

Full text not available from this repository.

Official URL: http://doi.org/10.1021/acs.bioconjchem.0c00667

Related URL: http://dx.doi.org/10.1021/acs.bioconjchem.0c00667

Abstract

Leishmaniasis, a vector-borne disease, is caused by intracellular parasite Leishmania donovani. Unlike most intracellular pathogens, Leishmania donovani are lodged in parasitophorous vacuoles and replicate within the phagolysosomes in macrophages. Effective vaccines against this disease are still under development, while the efficacy of the available drugs is being questioned owing to the toxicity for nonspecific distribution in human physiology and the reported drug-resistance developed by Leishmania donovani. Thus, a stimuli-responsive nanocarrier that allows specific localization and release of the drug in the lysosome has been highly sought after for addressing two crucial issues, lower drug toxicity and a higher drug efficacy. We report here a unique lysosome targeting polymeric nanocapsules, formed via inverse mini-emulsion technique, for stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line. A benign polymeric backbone, with a disulfide bonding susceptible to an oxidative cleavage, is utilized for the organelle-specific release of miltefosine. Oxidative rupture of the disulfide bond is induced by intracellular glutathione (GSH) as an endogenous stimulus. Such a stimuli-responsive release of the drug miltefosine in the lysosome of macrophage RAW 264.7 cell line over a few hours helped in achieving an improved drug efficacy by 200 times as compared to pure miltefosine. Such a drug formulation could contribute to a new line of treatment for leishmaniasis.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society
ID Code:134437
Deposited On:06 Jan 2023 09:23
Last Modified:06 Jan 2023 09:23

Repository Staff Only: item control page