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      A Novel Gel-Forming Solution Based on PEG-DSPE/Solutol HS 15 Mixed Micelles and Gellan Gum for Ophthalmic Delivery of Curcumin

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          Abstract

          Curcumin (Cur) is a naturally hydrophobic polyphenol with potential pharmacological properties. However, the poor aqueous solubility and low bioavailability of curcumin limits its ocular administration. Thus, the aim of this study was to prepare a mixed micelle in situ gelling system of curcumin (Cur-MM-ISG) for ophthalmic drug delivery. The curcumin mixed micelles (Cur-MMs) were prepared via the solvent evaporation method, after which they were incorporated into gellan gum gels. Characterization tests showed that Cur-MMs were small in size and spherical in shape, with a low critical micelle concentration. Compared with free curcumin, Cur-MMs improved the solubility and stability of curcumin significantly. The ex vivo penetration study revealed that Cur-MMs could penetrate the rabbit cornea more efficiently than the free curcumin. After dispersing the micelles in the gellan gum solution at a ratio of 1:1 ( v/ v), a transparent Cur-MM-ISG with the characteristics of a pseudoplastic fluid was formed. No obvious irritations were observed in the rabbit eyes after ocular instillation of Cur-MM-ISG. Moreover, Cur-MM-ISG showed a longer retention time on the corneal surface when compared to Cur-MMs using the fluorescein sodium labeling method. These findings indicate that biocompatible Cur-MM-ISG has great potential in ophthalmic drug therapy.

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          Curcumin: preventive and therapeutic properties in laboratory studies and clinical trials.

          Alex Strimpakos, Arya Sharma (2008)
          Curcumin is a natural polyphenol used in ancient Asian medicine. Since the first article referring to the use of curcumin to treat human disease was published in The Lancet in 1937, >2,600 research studies using curcumin or turmeric have been published in English language journals. The mechanisms implicated in the inhibition of tumorigenesis by curcumin are diverse and appear to involve a combination of antiinflammatory, antioxidant, immunomodulatory, proapoptotic, and antiangiogenic properties via pleiotropic effects on genes and cell-signaling pathways at multiple levels. The potentially adverse sequelae of curcumin's effects on proapoptotic genes, particularly p53, represent a cause for current debate. When curcumin is combined with some cytotoxic drugs or certain other diet-derived polyphenols, synergistic effects have been demonstrated. Although curcumin's low systemic bioavailability after oral dosing may limit access of sufficient concentrations for pharmacologic effects in tissues outside the gastrointestinal tract, chemical analogues and novel delivery methods are in preclinical development to overcome this barrier. This article provides an overview of the extensive published literature on the use of curcumin as a therapy for malignant and inflammatory diseases and its potential use in the treatment of degenerative neurologic diseases, cystic fibrosis, and cardiovascular diseases. Despite the breadth of the coverage, particular emphasis is placed on the prevention and treatment of human cancers.
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            Recent perspectives in ocular drug delivery.

            Sai H. S. Boddu, Ashim Mitra, Ripal Gaudana … (2009)
            Anatomy and physiology of the eye makes it a highly protected organ. Designing an effective therapy for ocular diseases, especially for the posterior segment, has been considered as a formidable task. Limitations of topical and intravitreal route of administration have challenged scientists to find alternative mode of administration like periocular routes. Transporter targeted drug delivery has generated a great deal of interest in the field because of its potential to overcome many barriers associated with current therapy. Application of nanotechnology has been very promising in the treatment of a gamut of diseases. In this review, we have briefly discussed several ocular drug delivery systems such as microemulsions, nanosuspensions, nanoparticles, liposomes, niosomes, dendrimers, implants, and hydrogels. Potential for ocular gene therapy has also been described in this article. In near future, a great deal of attention will be paid to develop non-invasive sustained drug release for both anterior and posterior segment eye disorders. A better understanding of nature of ocular diseases, barriers and factors affecting in vivo performance, would greatly drive the development of new delivery systems. Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders.
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              Polymeric micelles for ocular drug delivery: From structural frameworks to recent preclinical studies.

              Abhirup Mandal, Rohit Bisht, Ilva D Rupenthal … (2017)
              Effective intraocular drug delivery poses a major challenge due to the presence of various elimination mechanisms and physiological barriers that result in low ocular bioavailability after topical application. Over the past decades, polymeric micelles have emerged as one of the most promising drug delivery platforms for the management of ocular diseases affecting the anterior (dry eye syndrome) and posterior (age-related macular degeneration, diabetic retinopathy and glaucoma) segments of the eye. Promising preclinical efficacy results from both in-vitro and in-vivo animal studies have led to their steady progression through clinical trials. The mucoadhesive nature of these polymeric micelles results in enhanced contact with the ocular surface while their small size allows better tissue penetration. Most importantly, being highly water soluble, these polymeric micelles generate clear aqueous solutions which allows easy application in the form of eye drops without any vision interference. Enhanced stability, larger cargo capacity, non-toxicity, ease of surface modification and controlled drug release are additional advantages with polymeric micelles. Finally, simple and cost effective fabrication techniques render their industrial acceptance relatively high. This review summarizes structural frameworks, methods of preparation, physicochemical properties, patented inventions and recent advances of these micelles as effective carriers for ocular drug delivery highlighting their performance in preclinical studies.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Molecules
                Journal ID (iso-abbrev): Molecules
                Journal ID (publisher-id): molecules
                Title: Molecules
                Publisher: MDPI
                ISSN (Electronic): 1420-3049
                Publication date (Electronic): 24 December 2019
                Publication date Collection: January 2020
                Volume: 25
                Issue: 1
                Electronic Location Identifier: 81
                Affiliations
                [1 ]School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 102488, China; yxsaina@ 123456126.com (N.S.); dxiaoxv@ 123456163.com (X.D.); pqhuang@ 123456126.com (P.H.); ylt_svip@ 123456163.com (L.Y.); 17810257751@ 123456163.com (C.Y.); 18765804002@ 123456163.com (Y.L.); wangwenp6@ 123456163.com (W.W.); 18811385368@ 123456163.com (H.W.); yyc_zwq@ 123456163.com (Y.Y.); dyy9401@ 123456163.com (Y.D.); lengx11@ 123456126.com (X.L.); xb_yin@ 123456163.com (X.Y.)
                [2 ]School of pharmacy, Inner Mongolia Medical University, Hohhot 010110, China
                Author notes
                [* ]Correspondence: quchanghai@ 123456bucm.edu.cn (C.Q.); nijian@ 123456bucm.edu.cn (J.N.); Tel.: +86-010-6428-6407 (J.N.)
                [†]

                These two authors contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-5600-353X
                https://orcid.org/0000-0003-0198-3718
                Article
                Publisher ID: molecules-25-00081
                DOI: 10.3390/molecules25010081
                PMC ID: 6983186
                PubMed ID: 31878332
                SO-VID: 628b6cfd-f2f5-4ea6-984e-5bac3ff9c577
                Copyright © © 2019 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 November 2019
                Date accepted : 22 December 2019
                Categories
                Subject: Article

                Keywords: curcumin,mixed micelles,peg-dspe,solutol hs 15,gellan gum,ion-sensitive in situ gels,corneal permeation
                Data availability:
                Keywords: curcumin, mixed micelles, peg-dspe, solutol hs 15, gellan gum, ion-sensitive in situ gels, corneal permeation

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