Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

While biohybrid therapy shows promise, their further development into an "artificial pancreatic" system in diabetics also requires the management of the related immuneresponse triggered by such cellular therapies. Ideally this should be on a local level within the biohybrid device. This study relates to the design of sustained release formulations of the glucocorticoid soft drug loteprednol etabonate (LE) that are intended to locally suppress the immune response within the biohybrid devices, thereby warranting high local activity and reduced systemic side effects. Poly(D,L-lactic) acid (PLA) and poly(D,L-lactic glycolic acid (PLGA) microspheres of the soft corticosteroid loteprednol etabonate (LE) were prepared by solvent evaporation. A range of particles differing in particle size, nature of the polymer, emulsification method, and emulsifier were prepared and characterized. These results showed that the approach is able to customize slow release particles with predictable release characteristics over a period of days to month. Preliminary studies were performed with particles of a drug loading of 3.9 (+/- 0.2) %, and a mean particle diameter of 5 microm. In-vitro release studies indicated that these particles released drug over a period of three months. In vitro cell toxicity studies suggested that at higher concentrations (> 1 microM), unencapsulated LE showed some effect on the viability of the MIN-6 insuloma cell line, while the sustained release microspheres showed no cytotoxicity. The ability of these microspheres to provide localized immunosuppression has been evaluated in a set of early exploratory experiments with diabetic rats receiving islet transplantation. Animals treated using a biohybrid device loaded with microspheres showed improved results compared to those treated by delivery in solution form with an osmotic mini-pump. These results show the promise of localized glucocorticoid treatment by sustained release microspheres as a possible form of localized immunosuppression regimen. However, further confirmation is required before use in cell or organ transplantation.
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PMID:Feasibility of localized immunosuppression: 2. PLA microspheres for the sustained local delivery of a soft immunosuppressant. 2061 91

Long term retention of antimicrobials with effective drug concentration in gingival crevicular fluid (GCF) is of vital importance for the treatment of chronic periodontitis. In this study, a novel epithelial cell-targeting nanoparticle drug delivery system by conjugating minocycline-loaded poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) nanoparticles (NP-MIN) with RGD peptide were developed and administrated locally for targeting periodontitis epithelial cells and enhancing the treatment of periodontitis in dogs. Biodegradable NP-MIN was made with an emulsion/solvent evaporation technique. RGD peptide was conjugated to the surface of nanoparticles via Maleimide group reaction with hydrosulfide in RGD peptide (RGD-NP-MIN). Transmission electron microscopy examination and dynamic light scattering results revealed that RGD-NP-MIN had a sphere shape, with a mean diameter around 106nm. In vitro release of minocycline from RGD-NP-MIN showed that RGD modification did not change the remarkable sustained releasing characteristic of NP-MIN. To elucidate the interaction of RGD-NP and epithelial cells, RGD-NP binding, uptake and cellular internalization mechanisms by calu-3 cells were investigated. It was shown RGD modification significantly enhanced nanoparticles binding and uptake by Calu-3 cells, and RGD-NP uptake was an energy-dependent process through receptor-mediated endocytosis. Both clathrin-associated endocytosis and caveolae-dependent endocytosis pathway were involved in the RGD-NP uptake, and the intracellular transport of RGD-NP was related to lysosome and Golgi apparatus. Finally, in vivo pharmacokinetics of minocycline in the periodontal pockets and anti-periodontitis effects of RGD-NP-MIN on periodontitis-bearing dogs were evaluated. After local administration of RGD-NP-MIN, minocycline concentration in gingival crevicular fluid decreased slowly and maintained an effective drug concentration for a longer time than that of NP-MIN. Anti-periodontitis effects demonstrated that RGD-NP-MIN could significantly decrease symptoms of periodontitis, which was better than any other control group. These findings suggested that these epithelial cell-targeting nanoparticles offered a novel and effective local delivery system for the treatment of periodontitis.
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PMID:RGD functionalized polymeric nanoparticles targeting periodontitis epithelial cells for the enhanced treatment of periodontitis in dogs. 2619 7