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      Oral Delivery of Curcumin Polymeric Nanoparticles Ameliorates CCl 4-Induced Subacute Hepatotoxicity in Wistar Rats

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          Abstract

          Curcumin is the major bioactive compound of Curcuma longa, an important medicinal plant used in traditional herbal formulations since ancient times. In the present study, we report that curcumin nanoparticles (ηCur) protects Wistar rats against carbon tetrachloride (CCl 4)-induced subacute hepatotoxicity. Nanoparticles of sizes less than 220 nm with spherical shape were prepared using PLGA and PVA respectively as polymer and stabilizer. Test animals were injected via intraperitoneal route with 1 mL/kg CCl 4 (8% in olive oil) twice a week over a period of 8 weeks to induce hepatotoxicity. On the days following the CCl 4 injection, test animals were orally administered with either curcumin or its equivalent dose of ηCur. Behavioural observation, biochemical analysis of serum and histopathological examination of liver of the experimental animals indicated that ηCur offer significantly higher hepatoprotection compared to curcumin.

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          Fabrication of curcumin encapsulated PLGA nanoparticles for improved therapeutic effects in metastatic cancer cells.

          Murali Mohan Yallapu, Brij Gupta, Meena Jaggi … (2010)
          Curcumin, a natural polyphenolic compound, has shown promising chemopreventive and chemotherapeutic activities in cancer. Although phase I clinical trials have shown curcumin as a safe drug even at high doses, poor bioavailability and suboptimal pharmacokinetics largely moderated its anti-cancer activity in pre-clinical and clinical models. To improve its applicability in cancer therapy, we encapsulated curcumin in poly(lactic-co-glycolide) (PLGA) (biodegradable polymer) nanoparticles, in the presence of poly(vinyl alcohol) and poly(L-lysine) stabilizers, using a nano-precipitation technique. These curcumin nano-formulations were characterized for particle size, zeta potential, drug encapsulation, drug compatibility and drug release. Encapsulated curcumin existed in a highly dispersed state in the PLGA core of the nanoparticles and exhibited good solid-solid compatibility. An optimized curcumin nano-formulation (nano-CUR6) has demonstrated two and sixfold increases in the cellular uptake performed in cisplatin resistant A2780CP ovarian and metastatic MDA-MB-231 breast cancer cells, respectively, compared to free curcumin. In these cells, nano-CUR6 has shown an improved anti-cancer potential in cell proliferation and clonogenic assays compared to free curcumin. This effect was correlated with enhanced apoptosis induced by the nano-CUR6 formulation. Herein, we have also shown antibody conjugation compatibility of our PLGA-NP formulation. Results of this study suggest that therapeutic efficacy of curcumin may be enhanced by such PLGA nanoparticle formulations, and furthermore tumor specific targeted delivery of curcumin is made feasible by coupling of anti-cancer antibody to the NPs. Copyright 2010 Elsevier Inc. All rights reserved.
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            Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects.

            Michael Caplan, Judith Glöckner-Pagel, Sean Egan … (2004)
            Cystic fibrosis is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation, DeltaF508, results in the production of a misfolded CFTR protein that is retained in the endoplasmic reticulum and targeted for degradation. Curcumin is a nontoxic Ca-adenosine triphosphatase pump inhibitor that can be administered to humans safely. Oral administration of curcumin to homozygous DeltaF508 CFTR mice in doses comparable, on a weight-per-weight basis, to those well tolerated by humans corrected these animals' characteristic nasal potential difference defect. These effects were not observed in mice homozygous for a complete knockout of the CFTR gene. Curcumin also induced the functional appearance of DeltaF508 CFTR protein in the plasma membranes of transfected baby hamster kidney cells. Thus, curcumin treatment may be able to correct defects associated with the homozygous expression of DeltaF508 CFTR.
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              Novel Curcumin loaded nanoparticles engineered for Blood-Brain Barrier crossing and able to disrupt Abeta aggregates.

              Ruozi Barbara, Daniela Belletti, Francesca Pederzoli … (2017)
              The formation of extracellular aggregates built up by deposits of β-amyloid (Aβ) is a hallmark of Alzheimer's disease (AD). Curcumin has been reported to display anti-amyloidogenic activity, not only by inhibiting the formation of new Aβ aggregates, but also by disaggregating existing ones. However, the uptake of Curcumin into the brain is severely restricted by its low ability to cross the blood-brain barrier (BBB). Therefore, novel strategies for a targeted delivery of Curcumin into the brain are highly desired. Here, we encapsulated Curcumin as active ingredient in PLGA (polylactide-co-glycolic-acid) nanoparticles (NPs), modified with g7 ligand for BBB crossing. We performed in depth analyses of possible toxicity of these NPs, uptake, and, foremost, their ability to influence Aβ pathology in vitro using primary hippocampal cell cultures. Our results show no apparent toxicity of the formulated NPs, but a significant decrease of Aβ aggregates in response to Curcumin loaded NPs. We thus conclude that brain delivery of Curcumin using BBB crossing NPs is a promising future approach in the treatment of AD.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Polymers (Basel)
                Journal ID (iso-abbrev): Polymers (Basel)
                Journal ID (publisher-id): polymers
                Title: Polymers
                Publisher: MDPI
                ISSN (Electronic): 2073-4360
                Publication date (Electronic): 17 May 2018
                Publication date Collection: May 2018
                Volume: 10
                Issue: 5
                Electronic Location Identifier: 541
                Affiliations
                [1 ]Ratnam Institute of Pharmacy and Research, Nellore 524 346, India
                [2 ]College of Biological Science and Engineering, Shaanxi University of Technology, Hanzhong 723000, China
                [3 ]Department of Pharmaceutics, Jaya College of Paramedical Sciences, Tiruninravur 602 024, India; jose88prakash@ 123456gmail.com
                [4 ]Department of Pharmaceutics, Vels University, Chennai 600 117, India
                [5 ]Dapartment of Pharmacology, Vitamin D research institute, Shaanxi University of Technology, Hanzhong 723000, China; qishanshan101@ 123456126.com
                [6 ]Department of Integrative Plant Biology, Institute of Plant Genetics of the Polish Academy of Sciences, 34 Strzeszynska Street, PL-60-479 Poznan, Poland
                Author notes
                [* ]Correspondence: marslingregory@ 123456gmail.com (G.M.); fgre@ 123456igr.poznan.pl (G.F.); Tel.: +86-150-2901-9373 (G.M.); +48-61-655-0266 (G.F.)
                Author information
                https://orcid.org/0000-0002-2383-2382
                https://orcid.org/0000-0002-6745-3528
                Article
                Publisher ID: polymers-10-00541
                DOI: 10.3390/polym10050541
                PMC ID: 6415407
                PubMed ID: 30966575
                SO-VID: c3ebf85c-70e5-4d33-8456-2a1492d09261
                Copyright © © 2018 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 22 March 2018
                Date accepted : 11 May 2018
                Categories
                Subject: Article

                Keywords: curcumin,polymeric nanoparticles,subacute hepatotoxicity,histopathology,behavioral changes,liver enzymes
                Data availability:
                Keywords: curcumin, polymeric nanoparticles, subacute hepatotoxicity, histopathology, behavioral changes, liver enzymes

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