Termoreverzibilni mukoadhezivni in situ hidrogel za oftalmičku primjenu: dizajniranje i optimizacija koristeći kombinaciju polimera

The purpose of the study was to develop an optimized thermoreversible in situ gelling ophthalmic drug delivery system based on Pluronic F 127, containing moxifloxacin hydrochloride as a model drug. A 32 full factorial design was employed with two polymers Pluronic F 68 and Gelrite as independent variables used in combination with Pluronic F 127. Gelation temperature, gel strength, bioadhesion force, viscosity and in vitro drug release after 1 and 10 h were selected as dependent variables. Pluronic F 68 loading with Pluronic F 127 was found to have a significant effect on gelation temperature of the formulation and to be of importance for gel formation at temperatures 3336 ºC. Gelrite loading showed a positive effect on bioadhesion force and gel strength and was also found helpful in controling the release rate of the drug. The quadratic mathematical model developed is applicable to predicting formulations with desired gelation temperature, gel strength, bioadhesion force and drug release properties.Cilj rada bio je razvoj i optimizacija termoreverzibilnog sustava za isporuku lijekova koji gelira in situ. Sustav je napravljen na bazi Pluronic F 127, a sadrži moksifloksacin hidroklorid kao modelni lijek. U radu je primjenjeno 32 potpuno faktorijsko dizajniranje s dva polimera, Pluronic F 68 i Gelrite kao nezavisnim varijablama koji su kombinirani s Pluronic F 127. Kao zavisne varijable odabrane su temperatura geliranja, čvrstoća gela, jačina bioadhezije, viskoznost i in vitro oslobađanje lijeka nakon 1 i 10 h. Pronađeno je da Pluronic F 68 u kombinaciji s Pluronic F 127 ima značajan učinak na temperaturu geliranja u rasponu od 33 do 36 C. S druge strane, Gelrite ima povoljan učinak na jačinu bioadhezije, čvrstoću gela i oslobađanje lijeka. Razvijen je kvadratni matematički model pomoću kojeg se može predvidjeti temperatura geliranja, čvrstoća gela, jačina bioadhezije i oslobađanje ljekovite tvari

TCR signal strength controls thymic differentiation of discrete proinflammatory gamma delta T cell subsets

The mouse thymus produces discrete gd T cell subsets that make either interferon-g (IFN-g) or interleukin 17 (IL-17), but the role of the T cell antigen receptor (TCR) in this developmental process remains controversial. Here we show that Cd3g+/− Cd3d+/− (CD3 double-haploinsufficient (CD3DH)) mice have reduced TCR expression and signaling strength on gd T cells. CD3DH mice had normal numbers and phenotypes of ab thymocyte subsets, but impaired differentiation of fetal Vg6+ (but not Vg4+) IL-17- producing gd T cells and a marked depletion of IFN-g-producing CD122+ NK1.1+ gd T cells throughout ontogeny. Adult CD3DH mice showed reduced peripheral IFN-g+ gd T cells and were resistant to experimental cerebral malaria. Thus, TCR signal strength within specific thymic developmental windows is a major determinant of the generation of proinflammatory gd T cell subsets and their impact on pathophysiology

Diode-array UV spectrometric evidence for cooperative interactions in binary mixtures of Pluronics F77, F87, and F127

Iodine incorporation UV spectroscopy provides evidence that (PEOA-PPOB-PEOA) block copolymers (Pluronics) of related composition will aggregate either cooperatively or independently. Studying binary mixtures of Pluronics, selected from a series of Pluronics containing the same ratio of PEO:PPO (70% PEG, 30% PPO), allowed the effects of varying polymeric mass on the type of interaction observed to be investigated. Preliminary results indicate that the mass ratio of the PPO moieties determines the type of interaction observed

Pharmaceutical Therapies for Sealing of Permeabilized Cell Membranes in Electrical Injuriesa

Several years ago, we proposed that loss of cell membrane structural integrity by electroporation Is a substantial cause of tissue necrosis in victims of electrical trauma. Specifically, this involves the permeabilization of the lipid bilayer by thermal and electrical forces. We further suggested that certain mild surfactants in low concentration could induce sealing of permeabilized lipid bilayers and salvage of cells that had not been extensively heat-damaged. Successful restoration of membrane transport properties using the surfactant poloxamer 188 was reported in 1992. The purpose of this study is to further examine the response of electroporated rat skeletal muscle membranes to poloxamer 188 (P188) therapy by direct assay of membrane transport properties, Experimental evidence accumulated to date suggests that P188 is effective in sealing permeabilized cell membranes both in vitro and in vivo