Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Phenytoin (Ph), an antiepileptic drug, was reported to exhibit high wound healing activity. However, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop new single-dose electrospun nanoparticles-in-nanofibers (NPs-in-NFs) wound dressings that allow a well-controlled release of Ph. These NPs-in-NFs systems are based on enhanced chitosan (CS)/poly(ethylene oxide) (PEO) electrospun nanofibers (NFs) incorporating optimized Ph-loaded nanocarriers. First, a study was conducted to investigate Ph loading efficiency into polymeric nanocarriers of different types; pluronic nanomicelles and poly(lactic-co-glycolic) acids nanoparticles (PLGA NPs). The drug release profile from the nanocarriers was further optimized via lecithin coating. Second, different electrospinning parameters were manipulated to fabricate beads-free homogeneous NFs with optimized polymer ratios. Plain and Ph-loaded nanocarriers were characterized using Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), dynamic light scattering (DLS), and scanning electron microscopy (SEM). Both entrapment efficiency of Ph (EE%) and its release profile in phosphate buffer saline (PBS; pH 5.5), simulating the wound environment, were studied. Biodegradability, swelling, vapor permeability, and porosity of the developed Ph-loaded NPs-in-NFs wound dressings were investigated. Morphology of the NPs-in-NFs was also studied using SEM and confocal laser microscopy (CLSM). Besides, the release profiles of Ph from the optimized NPs-in-NFs were assessed. The newly developed wound dressings were evaluated in vitro for their cytotoxicity using human fibroblasts and in vivo using a wound healing mice model. Nanocarriers with particle size ranging from 100 to 180 nm were successfully prepared. All nanocarriers attained a high drug entrapment efficiency exceeding 94% and showed promising sustained release profiles compared to free Ph. Results also demonstrated that NFs incorporating the optimized lecithin-coated Ph-loaded PLGA NPs could be the most promising candidate for efficient wound healing. These NPs-in-NFs systems conferred a well-controlled and sustained release of Ph over 9 days. Moreover, they showed the best re-epithelization and healing quality during the in vivo study with minimal inflammatory and necrotic cells formation.
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PMID:Single-Dose Electrospun Nanoparticles-in-Nanofibers Wound Dressings with Enhanced Epithelialization, Collagen Deposition, and Granulation Properties. 2721 36

Blends of hydroxypropyl methylcellulose acetate succinate (HPMCAS) and dodecyl (C12)-tailed poly(N-isopropylacrylamide) (PNIPAm) were systematically explored as a model system to dispense the active ingredient phenytoin by rapid dissolution, followed by the suppression of drug crystallization for an extended period. Dynamic and static light scattering revealed that C12-PNIPAm polymers, synthesized by reversible addition-fragmentation chain-transfer polymerization, self-assembled into micelles with dodecyl cores in phosphate-buffered saline (PBS, pH 6.5). A synergistic effect on drug supersaturation was documented during in vitro dissolution tests by varying the blending ratio, with HPMACS primarily aiding in rapid dissolution and PNIPAm maintaining supersaturation. Polarized light and cryogenic transmission electron microscopy experiments revealed that C12-PNIPAm micelles maintain drug supersaturation by inhibiting both crystal nucleation and growth. Cross-peaks between the phenyl group of phenytoin and the isopropyl group of C12-PNIPAm in 2D 1H nuclear Overhauser effect (NOESY) spectra confirmed the existence of drug-polymer intermolecular interactions in solution. Phenytoin and polymer diffusion coefficients, measured by diffusion-ordered NMR spectroscopy (DOSY), demonstrated that the drug-polymer association constant increased with increasing local density of the corona chains, coincident with a reduction in C12-PNIPAm molecular weight. These findings demonstrate a new strategy for exploiting the versatility of polymer blends through the use of self-assembled micelles in the design of advanced excipients.
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PMID:Enhanced Performance of Blended Polymer Excipients in Delivering a Hydrophobic Drug through the Synergistic Action of Micelles and HPMCAS. 2828 37