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      Mucosal Applications of Poloxamer 407-Based Hydrogels: An Overview

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          Abstract

          Poloxamer 407, also known by the trademark Pluronic ® F127, is a water-soluble, non-ionic triblock copolymer that is made up of a hydrophobic residue of polyoxypropylene (POP) between the two hydrophilic units of polyoxyethylene (POE). Poloxamer 407-based hydrogels exhibit an interesting reversible thermal characteristic. That is, they are liquid at room temperature, but they assume a gel form when administered at body temperature, which makes them attractive candidates as pharmaceutical drug carriers. These systems have been widely investigated in the development of mucoadhesive formulations because they do not irritate the mucosal membranes. Based on these mucoadhesive properties, a simple administration into a specific compartment should maintain the required drug concentration in situ for a prolonged period of time, decreasing the necessary dosages and side effects. Their main limitations are their modest mechanical strength and, notwithstanding their bioadhesive properties, their tendency to succumb to rapid elimination in physiological media. Various technological approaches have been investigated in the attempt to modulate these properties. This review focuses on the application of poloxamer 407-based hydrogels for mucosal drug delivery with particular attention being paid to the latest published works.

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          Most cited references158

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          In situ-forming hydrogels--review of temperature-sensitive systems.

          In the past few years, an increasing number of in situ-forming systems have been reported in the literature for various biomedical applications, including drug delivery, cell encapsulation, and tissue repair. There are several possible mechanisms that lead to in situ gel formation: solvent exchange, UV-irradiation, ionic cross-linkage, pH change, and temperature modulation. The thermosensitive approach can be advantageous for particular applications as it does not require organic solvents, co-polymerization agents, or an externally applied trigger for gelation. In the last 2 decades, several thermosensitive formulations have been proposed. This manuscript focuses on aqueous polymeric solutions that form implants in situ in response to temperature change, generally from ambient to body temperature. It mainly reviews the characterization and use of polysaccharides, N-isopropylacrylamide copolymers, poly(ethylene oxide-b-propylene oxide-b-ethylene oxide) (poloxamer) and its copolymers, poly(ethylene oxide)/(D,L-lactic acid-co-glycolic acid) copolymers, and thermosensitive liposome-based systems.
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            Pluronic block copolymers: evolution of drug delivery concept from inert nanocarriers to biological response modifiers.

            Polymer nanomaterials have sparked a considerable interest as vehicles used for diagnostic and therapeutic agents; research in nanomedicine has not only become a frontier movement but is also a revolutionizing drug delivery field. A common approach for building a drug delivery system is to incorporate the drug within the nanocarrier that results in increased solubility, metabolic stability, and improved circulation time. With this foundation, nanoparticles with stealth properties that can circumvent RES and other clearance and defense mechanisms are the most promising. However, recent developments indicate that select polymer nanomaterials can implement more than only inert carrier functions by being biological response modifiers. One representative of such materials is Pluronic block copolymers that cause various functional alterations in cells. The key attribute for the biological activity of Pluronics is their ability to incorporate into membranes followed by subsequent translocation into the cells and affecting various cellular functions, such as mitochondrial respiration, ATP synthesis, activity of drug efflux transporters, apoptotic signal transduction, and gene expression. As a result, Pluronics cause drastic sensitization of MDR tumors to various anticancer agents, enhance drug transport across the blood brain and intestinal barriers, and causes transcriptional activation of gene expression both in vitro and in vivo. Collectively, these studies suggest that Pluronics have a broad spectrum of biological response modifying activities which make it one of the most potent drug targeting systems available, resulting in a remarkable impact on the emergent field of nanomedicine.
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              Micellization of Poly(ethylene oxide)-Poly(propylene oxide)-Poly(ethylene oxide) Triblock Copolymers in Aqueous Solutions: Thermodynamics of Copolymer Association

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                Author and article information

                Journal
                Pharmaceutics
                Pharmaceutics
                pharmaceutics
                Pharmaceutics
                MDPI
                1999-4923
                12 September 2018
                September 2018
                : 10
                : 3
                : 159
                Affiliations
                [1 ]Department of Health Sciences, University “Magna Græcia” of Catanzaro, Campus Universitario “S. Venuta”, Viale S. Venuta, I-88100 Catanzaro, Italy; giuliano.ele@ 123456gmail.com (E.G.); fresta@ 123456unicz.it (M.F.)
                [2 ]Department of Experimental and Clinical Medicine, University “Magna Græcia” of Catanzaro, Campus Universitario “S. Venuta”, Viale S. Venuta, I-88100 Catanzaro, Italy; paolino@ 123456unicz.it
                Author notes
                [* ]Correspondence: donatocosco@ 123456unicz.it ; Tel.: +39-0961-369-4119
                Author information
                https://orcid.org/0000-0002-4898-0365
                Article
                pharmaceutics-10-00159
                10.3390/pharmaceutics10030159
                6161217
                30213143
                5f24a95c-7e6a-4d63-b8cf-71c3271c5f81
                © 2018 by the authors.

                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
                : 31 July 2018
                : 10 September 2018
                Categories
                Review

                poloxamer 407,bioadhesion,mucosal drug delivery,hydrogels,thermo-reversible features

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