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      International Journal of Nanomedicine (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on the application of nanotechnology in diagnostics, therapeutics, and drug delivery systems throughout the biomedical field. Sign up for email alerts here.

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      Thermoreversible Pluronic ® F127-based hydrogel containing liposomes for the controlled delivery of paclitaxel: in vitro drug release, cell cytotoxicity, and uptake studies

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          Abstract

          Purpose

          To develop an in situ gel system comprising liposome-containing paclitaxel (PTX) dispersed within the thermoreversible gel (Pluronic ® F127 gel) for controlled release and improved antitumor drug efficiency.

          Methods

          The dialysis membrane and membrane-less diffusion method were used to investigate the in vitro drug release behavior. Differential scanning calorimetry (DSC) thermal analysis was used to investigate the “micellization” and “sol/gel transition” process of in situ gel systems. In vitro cytotoxicity and drug uptake in KB cancer cells were determined by MTT, intercellular drug concentration, and fluorescence intensity assay.

          Results

          The in vitro release experiment performed with a dialysis membrane model showed that the liposomal gel exhibited the longest drug-release period compared with liposome, general gel, and commercial formulation Taxol ®. This effect is presumably due to the increased viscosity of liposomal gel, which has the effect of creating a drug reservoir. Both drug and gel release from the in situ gel system operated under zero-order kinetics and showed a correlation of release of PTX with gel, indicating a predominating release mechanism of the erosion type. Dispersing liposomes into the gel replaced larger gel itself for achieving the same gel dissolution rate. Both the critical micelle temperature and the sol/gel temperature, detected by DSC thermal analysis, were shifted to lower temperatures by adding liposomes. The extent of the shifts depended on the amount of embedded liposomes. MTT assay and drug uptake studies showed that the treatment with PTX-loaded liposomal 18% Pluronic F127 yielded cytotoxicities, intercellular fluorescence intensity, and drug concentration in KB cells much higher than that of conventional liposome, while blank liposomal 18% Pluronic F127 gel was far less than the Cremophor EL ® vehicle and empty liposomes.

          Conclusions

          A thermosensitive hydrogel with embedded liposome is a promising carrier for hydrophobic anticancer agents, to be used in parenteral formulations for treating local cancers.

          Most cited references44

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          Controlled delivery of recombinant hirudin based on thermo-sensitive Pluronic F127 hydrogel for subcutaneous administration: In vitro and in vivo characterization.

          Here we investigated thermo-sensitive Pluronic(R) F127 (PF127) hydrogel for the controlled release of peptide and protein drugs after subcutaneous injection, using an antithrombotic polypeptide, recombinant hirudin variant-2 (rHV2), as the model drug. The in vitro release experiment performed with a membrane-less model at 37 degrees C showed that the release of antithrombotic activity of rHV2 from PF127 gel followed zero-order kinetics and correlated well with the weight percentage of PF127 dissolved, indicating a dissolution-controlled release mechanism. The in vivo result obtained after subcutaneous injection of rHV2-loaded PF127 gel in normal rats demonstrated that PF127 gel improved the bioavailability, prolonged the antithrombotic effect of rHV2, and induced detectable plasma rHV2 concentration for a longer time in comparison with rHV2 aqueous solution. Differential scanning calorimetry, dynamic light scattering and Fourier transform infrared spectroscopy provided evidence of the interaction between PF127 and rHV2, but such interaction was unlikely to interfere the feasibility of this drug delivery system. Our current in vitro and in vivo study suggested that PF127 gel may be useful as an injectable delivery vehicle for peptides and proteins with short half-lives to prolong their therapeutic effect, increase their bioavailability and improve the clinic outcome.
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            Study of the Gelation Process of Polyethylene Oxidea -Polypropylene Oxideb -Polyethylene Oxidea Copolymer (Poloxamer 407) Aqueous Solutions

            The gelation process of polyethylene oxidea -polypropylene oxideb -polyethylene oxidea copolymer (poloxamer 407) aqueous solutions is studied by means of FTIR spectroscopy, rheology, and differential scanning calorimetry (DSC). The C-O-C stretching bands of infrared spectra were found to shift toward higher wavenumbers with sol-gel transition, indicating that hydrogen bonding is not the driving force for gelation. Linear viscoelastic data provide an alternative method for gel point determination of these thermoreversible gels. The results obtained with this method are found to coincide with those obtained using DSC. Gel point temperatures determined by these methods are close to 14 degrees C for 25% (w/w) poloxamer 407 solutions and 10 degrees C for 30% (w/w) solutions. In gel state, the elastic modulus (G ') and dynamic viscosity (eta*) are found to be concentration and temperature independent for temperatures ranging from 20 to 35 degrees C. In light of our results, we suggest a mechanism of gelation based on micelles packing and entanglements.
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              Thermal and photochemical nitric oxide release from S-nitrosothiols incorporated in Pluronic F127 gel: potential uses for local and controlled nitric oxide release.

              The local delivery of nitric oxide (nitrogen monoxide, NO) by thermal or photochemical means to target cells or organs has a great potential in several biomedical applications, especially if the NO donors are incorporated into non-toxic viscous matrices. In this work, we have shown that the NO donors S-nitrosoglutathione (GSNO) and S-nitroso-N-acetylcysteine (SNAC) can be incorporated into F127 hydrogels, from where NO can be released thermally or photochemically (with lambda(irr)>480nm). High sensitivity differential scanning calorimetry (HSDSC) and a new spectrophotometric method, were used to characterize the micellization and the reversal thermal gelation processes of the F127 hydrogels containing NO donors, and to modulate the gelation temperatures to the range 29-32 degrees C. Spectral monitoring of the S-NO bond cleavage showed that the initial rates of thermal and photochemical NO release (ranging from 2 to 45 micromoll(-1)min(-1)) are decreased in the hydrogel matrices, relative to those obtained in aqueous solutions. This stabilization effect was assigned to a cage recombination mechanism and offers an additional advantage for the storage and handling of S-nitrosothiols. These results indicate that F127 hydrogels might be used for the thermal and photochemical delivery of NO from S-nitrosothiols to target areas in biomedical applications.
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                Author and article information

                Journal
                Int J Nanomedicine
                International Journal of Nanomedicine
                Dove Medical Press
                1176-9114
                1178-2013
                2011
                2011
                19 January 2011
                : 6
                : 151-166
                Affiliations
                [1 ] Department of Pharmaceutical Engineering, Wuhan Bioengineering Institute, Yangluo Economic Development Zone, Wuhan, People's Republic of China
                [2 ] School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, People's Republic of China
                [3 ] Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People's Republic of China
                Author notes
                Correspondence: Zhijun Yang, School of Chinese Medicine, Hong Kong Baptist University, 7 Baptist University Road, Hong Kong, People's Republic of China, Tel +852 3411 2961, Fax +852 3411 2461, Email yzhijun@ 123456hkbu.edu.hk
                Article
                ijn-6-151
                10.2147/IJN.S15057
                3075891
                21499415
                aace096c-299e-490f-8186-7ea3d6d99d1e
                © 2011 Nie et al, publisher and licensee Dove Medical Press Ltd.

                This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

                History
                Categories
                Original Research

                Molecular medicine
                cytotoxicity evaluation,drug uptake,controlled release
                Molecular medicine
                cytotoxicity evaluation, drug uptake, controlled release

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