Andrographolide (AG) is a diterpenoid lactone isolated from the leaves of Andrographis paniculata. AG is a potent and low-toxicity antileishmanial agent. Chemotherapy applications of AG are, however, seriously constrained because of poor bioavailability, short plasma half-life, and inappropriate tissue localization. Nanoparticulation of AG was therefore envisaged as a possible solution. AG nanoparticles (AGnp) loaded in 50:50 poly(DL-lactide-co-glycolic acid) were prepared for delivery into the monocyte-macrophage cells infested with the amastigote form of leishmanial parasite for evaluation in the chemotherapy of leishmaniasis. Particle characteristics of AGnp were optimized by proportionate application of a stabilizer, polyvinyl alcohol (PVA). Physicochemical characterization of AGnp by photon correlation spectroscopy exhibited an average particle size of 173 nm and zeta potential of -34.8 mV. Atomic force microscopy visualization revealed spherical nanoparticles with a smooth surface. Antileishmanial activity was found to be significant for the nanoparticle preparation with 4% PVA (IC50 34 μM) in about one-fourth of the dosage of the pure compound AG (IC50 160 μM). AGnp therefore have significant potential to target the infested macrophage cells and prove valuable in chemotherapy of neglected tropical diseases such as leishmaniasis. © 2010 Roy et al, publisher and licensee Dove Medical Press Ltd.

P ROY

S DAS

T BERA

S MONDOL

A MUKHERJEE

Fulltext

University of Calcutta (informally known as Calcutta University or CU) is a collegiate public state university located in Kolkata, West Bengal, India.&nbsp;Within India it is recognized as a &quot;Five-Star University&quot; and accredited &quot;A&quot; Grade by National Assessment and Accreditation Council.

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The University of Calcutta has secured the Fifth position among the Universities of India in the prestigious &quot;Indian University Ranking 2019&quot; list, released by the NIRF of the Ministry of Human Resource Development, Government of India.

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It was established on 24 January 1857, and was one of the first institutions in Asia to be established as a multidisciplinary and Western-style university. Its alumni and faculty include several heads of state, heads of government, social reformers, prominent artists, only academy award winner and Dirac medal winner in India, many Fellows of the Royal Society and five Nobel laureates as of 2019 which is highest in South Asia.

University Of Calcutta

Andrographolide nanoparticles in leishmaniasis: characterization and in vitro evaluations.

International Journal of Nanomedicine

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. © 2013 Springer Science+Business Media New York.

Pharmaceutical Research

Engineered andrographolide nanoparticles mitigate paracetamol hepatotoxicity in mice

Visceral leishmaniasis (VL) is a chronic protozoan infection in humans associated with significant global morbidity and mortality. There is an urgent need to develop drugs and strategy that will improve therapeutic response for effective clinical treatment of drug resistant VL. To address this need, andrographolide (AG) nanoparticles were designed with P-gp efflux inhibitor vitamin E TPGS (D-α-tocopheryl polyethyleneglycol 1000 succinate) for sensitivity against drug resistant Leishmania strains. AG loaded PLGA (50:50) nanoparticles (AGnps) stabilized by vitamin E TPGS were prepared for delivery into macrophage cells infested with sensitive and drug resistant amastigotes of Leishmania parasites. Physico-chemical characterization of AGnps by photon correlation spectroscopy exhibited an average particle size of 179.6 nm, polydispersity index of 0.245 and zeta potential of -37.6 mV. Atomic force microscopy and transmission electron microscopy visualization revealed spherical nanoparticles with smooth surfaces. AGnps displayed sustained AG release up to 288 hours as well as minimal particle aggregation and drug loss even after three months study period. Antileishmanial activity as revealed from selectivity index in wild-type strain was found to be significant for AGnp with TPGS in about one-tenth of the dosage of the free AG and one-third of the dosage of the AGnp without TPGS. Similar observations were also found in case of in vitro generated drug resistant and field isolated resistant strains of Leishmania. Cytotoxicity of AGnp with and without TPGS was significantly less than standard antileishmanial chemotherapeutics like amphotericin B, paromomycin or sodium stibogluconate. Macrophage uptake of AGnps was almost complete within one hour as evident from fluorescent microscopy studies. Thus, based on these observations, it can be concluded that the low-selectivity of AG in in vitro generated drug resistant and field isolated resistant strains was improved in case of AG nanomedicines designed with vitamin E TPGS. © 2013 Mondal et al.

PLoS ONE

In Vitro susceptibilities of wild and drug resistant Leishmania donovani amastigote stages to andrographolide nanoparticle: Role of vitamin e derivative TPGS for nanoparticle efficacy

Success in cancer chemotherapy relies on efficient delivery of anti-neoplastic drugs, with minimal side-effects on non-cancerous cells. Nanoparticulation of prospective anti-cancer drugs, that were deemed unsuitable due to short biological half life, poor water solubility and low cellular permeability, has been hypothesized to generate superior chemotherapeutic agents, leading to reduced non-specific action and fewer side-effects. In lieu of the above, different synthetic modulations on the putative anti-cancer compound andrographolide (AG) were explored to improve its therapeutic efficiency. Our results indicated that PLGA-nanoparticulation of andrographolide diterpenoid enhanced its anti-cancer properties three fold. Chitosan coating of AG nanoparticles further accentuated cellular localization, induced G1 cell cycle arrest and increased cellular toxicity and apoptosis in MCF-7 cells. The charge modulated nanoparticles were seen to traverse more efficiently through the cytoplasm and accumulate in the nucleus, thus enhancing their anti-proliferative efficacy. In vivo studies confirm that the nanoparticles reduced tumor weight by 68.21% as compared to 24.7% by AG, and increased the life span of mice infected with Ehrlich ascites carcinoma (EAC) by 78.08% as compared to 23.5% for AG alone. This was achieved through development of slow release-type nanoparticle cargo delivery devices, and enhanced the efficiency of AGnps for targeting cancer cells. AG nanoparticles also showed sufficient promise as safe anti-cancer drugs since they had minimal impact on animal hematology. Hence, we successfully prepared non-toxic and delivery-efficient andrographolide nanoparticles, and established for the first time that PLGA-nanoparticulation of andrographolide and additional chitosan coating increased its anti-cancer efficacy in human breast cancer cells and mouse EAC model. © 2012 Bentham Science Publishers.

Current Pharmaceutical Biotechnology

Nanoparticle engineering enhances anticancer efficacy of andrographolide in MCF-7 cells and mice bearing EAC

Silymarin (Sm) is a polyphenolic component extracted from Silybum marianum. It is an antioxidant, traditionally used as an immunostimulant, hepatoprotectant, and dietary supplement. Relatively recently, Sm has proved to be a valuable chemopreventive and a useful antineoplastic agent. Medical success for Sm is, however, constrained by very low aqueous solubility and associated biopharmaceutical limitations. Sm flavonolignans are also susceptible to ion-catalyzed degradation in the gut. Proven antihepatotoxic activity of Sm cannot therefore be fully exploited in acute chemical poisoning conditions like that in paracetamol overdose. Moreover, a synchronous delivery that is required for hepatic regeneration is difficult to achieve by itself. This work is meant to circumvent the inherent limitations of Sm through the use of nanotechnology. Sm nanoparticles (Smnps) were prepared by nanoprecipitation in polyvinyl alcohol stabilized Eudragit RS100(®) polymer (Rohm Pharma GmbH, Darmstadt, Germany). Process parameter optimization provided 67.39% entrapment efficiency and a Gaussian particle distribution of average size 120.37 nm. Sm release from the nanoparticles was considerably sustained for all formulations. Smnps were strongly protective against hepatic damage when tested in a paracetamol overdose hepatotoxicity model. Nanoparticles recorded no animal death even when administered after an established paracetamol-induced hepatic necrosis. Preventing progress of paracetamol hepatic damage was traced for an efficient glutathione regeneration to a level of 11.3 μmol/g in hepatic tissue due to Smnps.

Silymarin nanoparticle prevents paracetamol-induced hepatotoxicity.

Phytopharmacy

Kalmegh

International Journal of Gynecology & Obstetrics

Journal of Medicinal Chemistry

Neglected Tropical Diseases: Multi-Target-Directed Ligands in the Search for Novel Lead Candidates againstTrypanosomaandLeishmania

Molecular Pharmaceutics

Kahalalide F, an Antitumor Depsipeptide in Clinical Trials, and Its Analogues as Effective Antileishmanial Agents

Preparation, characterization and in-vitro evaluation of sustained release protein-loaded nanoparticles based on biodegradable polymers

Andrographolide nanoparticles in leishmaniasis: Characterization and in vitro evaluations

Journal	International Journal of Nanomedicine
Publisher	DOVE MEDICAL PRESS LTD
ISSN	1176-9114
Open Access	Yes