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Engineered Andrographolide Nanoparticles Mitigate Paracetamol Hepatotoxicity in Mice

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ABSTRACT

Purpose

Paracetamol (acetaminophen, APAP) overdose is often fatal due to progressive and irreversible hepatic necrosis. The aim of this work was to design Andrographolide (AG) loaded nanoparticles to prevent similar hepatic necrosis.

Methods

Functionalized AG-loaded PLGA nanoparticles carrying different densities of heparin were prepared following a facile emulsion solvent evaporation technique. Nanoparticle morphology, loading and release kinetics were studied. Hepatic localization of the nanoparticles was investigated in both normal and APAP damaged conditions using FITC fluorescent probe. Different serum parameters and liver histopathology were further examined as indicators of hepatic condition before and after treatment.

Result

A collection of heparin functionalized AG-loaded PLGA nanoparticles were designed. Low amount of heparin on the particle surface could rapidly localize the nanoparticles up to the liver. The new functionalized AG nanoparticles affect efficient hepatoprotection in experimental mouse APAP overdose conditions. AG nanoparticle hepatoprotection was due to the rapid regeneration of antioxidant capacity and hepatic GSH store.

Conclusions

Engineered nanoparticles loaded with AG provided a fast protection in APAP induced acute liver failure.

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Abbreviations

AG:

andrographolide

AGnp:

andrographolide nanoparticle

APAP:

N-acetyl-p-aminophenol

BCS:

biopharmaceutical classification system

CT:

computed tomography

CTCF:

corrected total cell fluorescence

DILD:

drug induced liver damage

FITC:

fluorescein isothiocyanate

Fnp:

fluorescent nanoparticle

Hep:

heparin

Hep-Fnp:

heparinized fluorescent nanoparticle

Hep-AGnp:

heparin functionalized andrographolide nanoparticle

KCE:

known chemical entity

MDA:

malondialdehyde

Mrp:

multi-drug resistance protein

NAC:

N-acetyl cysteine

NAPQI:

N-acetyl-para benzoquinoneimine

PEO:

polyethylene oxide

PLGA:

poly (D-L-lactide-co-glycolic acid)

PPO:

polypropylene oxide

ROS:

reactive oxygen species

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ACKNOWLEDGMENTS AND DISCLOSURES

Senior Research Fellowships to Partha Roy and Suvadra Das from Indian Council for Medical Research and Council of Scientific and Industrial Research respectively, is gratefully acknowledged. This work is partly funded from the Department of Biotechnology Govt of India nanoscience and nanotechnology grants. Dr. Runa Ghosh Auddy would like to thank CRNN, University of Calcutta for financial assistance.

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Authors and Affiliations

  1. Division of Pharmaceutical and Fine Chemicals Technology Department of Chemical Technology, University of Calcutta, 92, APC Road, Kolkata, 700009, India

    Partha Roy, Suvadra Das, Runa Ghosh Auddy, Achintya Saha & Arup Mukherjee

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  1. Partha Roy
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  2. Suvadra Das
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  3. Runa Ghosh Auddy
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Correspondence to Arup Mukherjee.

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Roy, P., Das, S., Auddy, R.G. et al. Engineered Andrographolide Nanoparticles Mitigate Paracetamol Hepatotoxicity in Mice. Pharm Res 30, 1252–1262 (2013). https://doi.org/10.1007/s11095-012-0964-5

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  • DOI: https://doi.org/10.1007/s11095-012-0964-5

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