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      Polymeric Nanoparticles for Increasing Oral Bioavailability of Curcumin

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          Abstract

          Despite the promising biological and antioxidant properties of curcumin, its medical applications are limited due to poor solubility in water and low bioavailability. Polymeric nanoparticles (NPs) adapted to oral delivery may overcome these drawbacks. Properties such as particle size, zeta potential, morphology and encapsulation efficiency were assessed. Then, the possibility of storing these NPs in a solid-state form obtained by freeze-drying, in vitro curcumin dissolution and cytocompatibility towards intestinal cells were evaluated. Curcumin-loaded Eudragit ® RLPO (ERL) NPs showed smaller particle diameters (245 ± 2 nm) and better redispersibility after freeze-drying than either poly(lactic- co-glycolic acid) (PLGA) or polycaprolactone (PCL) NPs. The former NPs showed lower curcumin encapsulation efficiency (62%) than either PLGA or PCL NPs (90% and 99%, respectively). Nevertheless, ERL NPs showed rapid curcumin release with 91 ± 5% released over 1 h. The three curcumin-loaded NPs proposed in this work were also compatible with intestinal cells. Overall, ERL NPs are the most promising vehicles for increasing the oral bioavailability of curcumin.

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          Nanoparticles as potential oral delivery systems of proteins and vaccines: a mechanistic approach.

          Anne des Rieux, Virginie Fievez, Marie Garinot … (2006)
          Peptides and proteins remain poorly bioavailable upon oral administration. One of the most promising strategies to improve their oral delivery relies on their association with colloidal carriers, e.g. polymeric nanoparticles, stable in gastrointestinal tract, protective for encapsulated substances and able to modulate physicochemical characteristics, drug release and biological behavior. The mechanisms of transport of these nanoparticles across intestinal mucosa are reviewed. In particular, the influence of size and surface properties on their non-specific uptake or their targeted uptake by enterocytes and/or M cells is discussed. Enhancement of their uptake by appropriate cells, i.e. M cells by (i) modeling surface properties to optimize access to and transport by M cells (ii) identifying surface markers specific to human M cell allowing targeting to M cells and nanoparticles transcytosis is illustrated. Encouraging results upon in vivo testing are reported but low bioavailability and lack of control on absorbed dose slow down products development. Vaccines are certainly the most promising applications for orally delivered nanoparticles.
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            Biological properties of curcumin-cellular and molecular mechanisms of action.

            B Lokesh, M. Vijaykumar, Aaron Joe (2003)
            Curcuminoids, a group of phenolic compounds isolated from the roots of Curcuma longa (Zingiberaceae), exhibit a variety of beneficial effects on health and on events that help in preventing certain diseases. A vast majority of these studies were carried out with curcumin (diferuloyl methane), which is a major curcuminoid. The most detailed studies using curcumin include anti-inflammatory, antioxidant, anticarcinogenic, antiviral, and antiinfectious activities. In addition, the wound healing and detoxifying properties of curcumin have also received considerable attention. As a result of extensive research on the therapeutic properties of curcumin, some understanding on the cellular, molecular, and biochemical mechanism of action of curcumin is emerging. These findings are summarized in this review.
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              Pharmacokinetics of curcumin-loaded PLGA and PLGA-PEG blend nanoparticles after oral administration in rats.

              Najeh Maissar Khalil, Thuane Nascimento, Diani Meza Casa … (2013)
              The aim of this study was to assess the potential of nanoparticles to improve the pharmacokinetics of curcumin, with a primary goal of enhancing its bioavailability. Polylactic-co-glycolic acid (PLGA) and PLGA-polyethylene glycol (PEG) (PLGA-PEG) blend nanoparticles containing curcumin were obtained by a single-emulsion solvent-evaporation technique, resulting in particles size smaller than 200 nm. The encapsulation efficiency was over 70% for both formulations. The in vitro release study showed that curcumin was released more slowly from the PLGA nanoparticles than from the PLGA-PEG nanoparticles. A LC-MS/MS method was developed and validated to quantify curcumin in rat plasma. The nanoparticles were orally administered at a single dose in rats, and the pharmacokinetic parameters were evaluated and compared with the curcumin aqueous suspension. It was observed that both nanoparticles formulations were able to sustain the curcumin delivery over time, but greater efficiency was obtained with the PLGA-PEG nanoparticles, which showed better results in all of the pharmacokinetic parameters analyzed. The PLGA and PLGA-PEG nanoparticles increased the curcumin mean half-life in approximately 4 and 6h, respectively, and the C(max) of curcumin increased 2.9- and 7.4-fold, respectively. The distribution and metabolism of curcumin decreased when it was carried by nanoparticles, particularly PLGA-PEG nanoparticles. The bioavailability of curcumin-loaded PLGA-PEG nanoparticles was 3.5-fold greater than the curcumin from PLGA nanoparticles. Compared to the curcumin aqueous suspension, the PLGA and PLGA-PEG nanoparticles increased the curcumin bioavailability by 15.6- and 55.4-fold, respectively. These results suggest that PLGA and, in particular, PLGA-PEG blend nanoparticles are potential carriers for the oral delivery of curcumin. Copyright © 2012 Elsevier B.V. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Antioxidants (Basel)
                Journal ID (iso-abbrev): Antioxidants (Basel)
                Journal ID (publisher-id): antioxidants
                Title: Antioxidants
                Publisher: MDPI
                ISSN (Electronic): 2076-3921
                Publication date (Electronic): 24 March 2018
                Publication date Collection: April 2018
                Volume: 7
                Issue: 4
                Electronic Location Identifier: 46
                Affiliations
                [1 ]Université de Lorraine, CITHEFOR, F-54000 Nancy, France; anita.umerska@ 123456univ-lorraine.fr (A.U.); Isabelle.Raeth@ 123456univ-lorraine.fr (I.F.-R.); florence.colin88@ 123456gmail.com (F.C.); philippe.maincent@ 123456univ-lorraine.fr (P.M.); anne.sapin@ 123456univ-lorraine.fr (A.S.-M.)
                [2 ]Departamento de Ciencias y Tecnología Farmacéuticas, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 758-0150 Santiago, Chile; foyarzuna@ 123456ciq.uchile.cl (F.O.-A.); magabrielavillamizarsarmiento@ 123456gmail.com (M.G.V.-S.)
                Author notes
                [* ]Correspondence: caroline.gaucher@ 123456univ-lorraine.fr ; Tel.: +33-3-72-74-73-49
                Author information
                https://orcid.org/0000-0002-4981-8247
                https://orcid.org/0000-0002-0886-5522
                https://orcid.org/0000-0002-9402-8164
                Article
                Publisher ID: antioxidants-07-00046
                DOI: 10.3390/antiox7040046
                PMC ID: 5946112
                PubMed ID: 29587350
                SO-VID: e3b8018d-ae47-4402-a36a-ed29a96ab354
                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 : 27 February 2018
                Date accepted : 22 March 2018
                Categories
                Subject: Article

                Keywords: curcumin,nanoparticles,plga,pcl,eudragit,cytocompatibility,intestinal cells,single emulsion-solvent evaporation method
                Data availability:
                Keywords: curcumin, nanoparticles, plga, pcl, eudragit, cytocompatibility, intestinal cells, single emulsion-solvent evaporation method

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