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Title: | Redox-Responsive Nanocapsules for the Spatiotemporal Release of Miltefosine in Lysosome: Protection against Leishmania | Authors: | Tiwari, Rajeshwari Banerjee, Saswati Tyde, Deepak Das Saha, Krishna ETHIRAJAN, Anitha Mukherjee, Niladri Chattopadhy, Samit PRAMANIK, Sumit Das, Amitava |
Issue Date: | 2021 | Publisher: | AMER CHEMICAL SOC | Source: | BIOCONJUGATE CHEMISTRY, 32 (2) , p. 245 -253 | 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. | Notes: | Pramanik, SK (corresponding author), CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India.; Mukherjee, N (corresponding author), CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, India.; Chattopadhy, S (corresponding author), BITS Pilani, Pilani 403726, Goa, India.; Das, A (corresponding author), Indian Inst Sci Educ & Res Kolkata, Mohanpur 741246, W Bengal, India. niladrizoology@gmail.com; sumitpramanik@csmcri.res.in; a.das@csmri.res.in |
Other: | Pramanik, SK (corresponding author), CSIR Cent Salt & Marine Chem Res Inst, Bhavnagar 364002, Gujarat, India. Mukherjee, N (corresponding author), CSIR Indian Inst Chem Biol, Canc Biol & Inflammatory Disorder Div, Kolkata 700032, India. Chattopadhy, S (corresponding author), BITS Pilani, Pilani 403726, Goa, India. Das, A (corresponding author), Indian Inst Sci Educ & Res Kolkata, Mohanpur 741246, W Bengal, India. niladrizoology@gmail.com; sumitpramanik@csmcri.res.in; a.das@csmri.res.in | Document URI: | http://hdl.handle.net/1942/33881 | ISSN: | 1043-1802 | e-ISSN: | 1520-4812 | DOI: | 10.1021/acs.bioconjchem.0c00667 | ISI #: | WOS:000621366800004 | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2022 |
Appears in Collections: | Research publications |
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File | Description | Size | Format | |
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Bioconjugate Chemistry 2021_A.Ethirajan-author version.pdf | Peer-reviewed author version | 1.4 MB | Adobe PDF | View/Open |
acs.bioconjchem.0c00667.pdf Restricted Access | Published version | 4.47 MB | Adobe PDF | View/Open Request a copy |
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