15 research outputs found
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In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery
This study evaluated the use of Pluronic F127 and Pluronic F68 as excipients for formulating in situ gelling systems for ocular drug delivery. Thermal transitions have been studied in aqueous solutions of Pluronic F127, Pluronic F68 as well as their binary mixtures using differential scanning calorimetry, rheological measurements, and dynamic light scattering. It was established that the formation of transparent gels at physiologically relevant temperatures is observed only in the case of 20 wt % of Pluronic F127. The addition of Pluronic F68 to Pluronic F127 solutions increases the gelation temperature of binary formulation to above physiological range of temperatures. The biocompatibility evaluation of these formulations using slug mucosa irritation assay and bovine corneal erosion studies revealed that these polymers and their combinations do not cause significant irritation. In vitro drug retention study on glass surfaces and freshly excised bovine cornea showed superior performance of 20 wt % Pluronic F127 compared to other formulations. In addition, in vivo studies in rabbits demonstrated better retention performance of 20 wt % Pluronic F127 compared to Pluronic F68. These results confirmed that 20 wt % Pluronic F127 offers an attractive ocular formulation that can form a transparent gel in situ under physiological conditions with minimal irritation
Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations : design, characterisation, toxicity and transcorneal permeation studies
This study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using {DSC} and FT-IR. The gelation temperature (Tsol-gel), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. {DSC} and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used. {P188} modified the Tsol/gel of {P407} bringing it close to eye temperature (35°C) compared with the formulation containing {P407} alone. Moreover, gels that comprised {P407} and {P188} exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations {PP11} and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control {KT} release as only 48 of the {KT} released within 12 h. In addition, the HET-CAM and {BCOP} tests confirmed the non-irritancy of {KT} loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. {MTT} assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with {KT} showed reasonable and acceptable percent cell viability compared with control samples
In situ gelling systems based on Pluronic F127/Pluronic F68 formulations for ocular drug delivery
The New Workforce Generation: Understanding the Problems Facing Parental Involvement in Jordanian Kindergartens
Formulation development, optimization, and in vitro assessment of thermoresponsive ophthalmic pluronic F127-chitosan in situ
C-Nap1 mutation affects centriole cohesion and is associated with a Seckel-like syndrome in cattle
Molecular pathophysiology of fragile x-associated tremor/ataxia syndrome and perspectives for drug development
Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disorder manifesting in carriers of 55 to 200 CGG repeats in the 5' untranslated region (UTR) of the fragile X mental retardation gene (FMR1). FXTAS is characterized by enhanced FMR1 transcription and the accumulation of CGG repeat-containing FMR1 messenger RNA in nuclear foci, while the FMRP protein expression levels remain normal or moderately low. The neuropathological hallmark in FXTAS is the presence of intranuclear, ubiquitin-positive inclusions that also contain FMR1 transcript. Yet, the complete protein complement of FXTAS inclusions and the molecular events that trigger neuronal death in FXTAS remain unclear. In this review, we present the two most accepted toxicity mechanisms described so far, namely RNA gain-of-function and protein gain-of-function by means of repeat-associated non-AUG translation, and discuss current experimental and computational strategies to better understand FXTAS pathogenesis. Finally, we review the current perspectives for drug development with disease-modifying potential for FXTAS.Our research received funding from the European Union Seventh Framework Programme (FP7/2007-2013), through the European Research Council, under grant agreement RIBOMYLOME_ 309545 (Gian Gaetano Tartaglia), and from the Fundació La Marató de TV3 (20142731). We also acknowledge support from the Spanish Ministry of Economy and Competitiveness (BFU2011-26206 and BFU2014-55054-P) and “Centro de Excelencia Severo Ochoa 2013– 2017” (SEV-2012-0208
Curcumin‐loaded Pluronic ®
Antimicrobial photodynamic therapy (aPDT) is promising for oral decontamination. Curcumin has been used as photosensitizer; however, the hydrophobic properties can negatively affect aPDT. This study evaluated the aPDT efficacy using Cur-loaded Pluronic® F-127 micelles against Streptococcus mutans and Candida albicans biofilms. Micelles characterization was performed by zeta potential, dynamic light scattering, transmission electron microscopy, absorption and fluorescence spectroscopy. Cur concentrations, cell viability by CFU mL−1 and confocal microscopy were determined. Data were analyzed by parametric and nonparametric tests under 5%. Cur-loaded Pluronic® F-127 exhibited spherical shape, suitable particle size (≤100 nm), adequate polydispersity index, best stability, lower photodegradation and autoaggregation compared to unloaded-Cur. Both microorganisms were sensitive to Cur-loaded Pluronic® F-127 micelles aPDT, with minimum inhibitory concentration (MIC) of 270 μm and 2.1093 μm for S. mutans and C. albicans suspended culture, respectively. Cur-loaded Pluronic® F-127 aPDT exhibited antibacterial/antifungal effect against the biofilms (~3 log10 reduction; P ≤ 0.05); however, similar to unloaded (P ≥ 0.05). Confocal images confirmed these results. Cur-loaded Pluronic® F-127 micelles exhibited good photo-chemical properties and may be a viable alternative to deliver Cur and to improve aPDT effect during the treatment of dental caries. Moreover, Pluronic® micelles can enhance the solubility, stability, permeability and control the release of Cur