• Lindholm Mckay posted an update 6 months, 1 week ago

    Both showed highest OVA encapsulation at 67% and 73%, and sustained OVA release in SIF (96 hrs) at 65% and 64% respectively. BET results showed that nanopores were not blocked during surface modification. CD and SDS-PAGE showed that OVA conformational structure did not change after release from nanoparticles. Glycopyrronium bromide, a synthetic anticholinergic agent used to treat patients with chronic obstructive pulmonary disease (COPD), is eliminated from the body by renal excretion and therefore systemic exposure is expected to be increased in patients with decreasing renal function. Despite enrollment of patients with decreasing renal function to evaluate the impact of renal impairment on the pharmacokinetics of glycopyrronium in clinical studies, no patients with severe renal impairment were included. A physiologically based pharmacokinetic (PBPK) model was developed in patients with COPD with normal renal function and used to predict systemic exposure of glycopyrronium in patients with severe renal impairment. The model accurately predicted plasma concentration-time profiles in patients with normal renal function, and mild and moderate renal impairment; the predicted and observed AUC and Cmax in these populations were similar. Compared to patients with normal renal function, a 1.20-, 1.45-, and 1.59-fold increase AUC was predicted in patients with mild, moderate, and severe renal impairment, respectively, suggesting dose adjustment is not necessary in patients with renal impairment. In conclusion, PBPK models, verified with clinical study data from patients with normal renal function, can potentially be used to predict the pharmacokinetics and recommended dose adjustment for patients with renal impairment. Cytochrome P450 1B1 (CYP1B1) has been reported to have a major role in metabolizing arachidonic acid (AA) into cardiotoxic metabolites, mid-chain hydroxyeicosatetraenoic acids (HETEs). Recently, we have shown that fluconazole decreases the level of mid-chain HETEs in human liver microsomes. Therefore, the objectives of this study were to investigate the effect of fluconazole on CYP1B1 mediated mid-chain HETEs and to explore its potential protective effect against angiotensin II- (Ang II)-induced cellular hypertrophy. To do this, Sprague Dawley rats were injected intraperitoneally with a single dose of fluconazole (20 mg/kg) for 24 h. Also, H9c2 and RL-14 cells were treated with 10 μM Ang II in the presence and absence of 50 μM fluconazole for 24 h. Our results demonstrated that treatment of rats with fluconazole significantly decreased the expression of CYP1B1 enzyme and the level of mid-chain HETEs in the heart. RepSox ic50 Furthermore, fluconazole was able to attenuate Ang-II-induced cellular hypertrophy as evidenced by a significant down-regulation of hypertrophic markers; β-myosin heavy chain (MHC)/ α-MHC and brain natriuretic peptide (BNP) as well as cell surface area. In conclusion, our findings indicate that fluconazole protects against Ang II-induced cellular hypertrophy by repressing CYP1B1 and its associated mid-chain HETEs. A wound indicates a discontinuity in the epithelial integrity of the skin along with structural and functional disruption of the underlying normal tissue. The study focused on chitosan stabilized silver nanoparticles (CH-AgNP) further incorporated in a chitosan-based (CH-AgNP-CHF) film for wound healing. Dual advantages of chitosan as a wound-healing agent in addition to the antimicrobial property of CH-AgNP nanoparticles was explored. Based on preliminary trials, 1-2 % w/v chitosan as film former, 15-25% w/v glycerin as plasticizer and teflon as casting surface was selected. The optimized CH-AgNP-CHF had tensile strength 1.39 ± 0.009 N/mm2, % Elongation 33.33 ± 1.634, 76.66 ± 0.584 % degree of swelling, WVTR of 2024.43 ± 32.78 gm.m-2 day-1 and 1144.57 ± 13.45 gm.m-2 day-1 after 24 h and after 21 days respectively. The CH-AgNP-CHF reported highest % inhibition of 62.22 ± 0.91 against Escherichia coli as compared to chitosan solution, chitosan film and CH-AgNP solution. Based on in-vivo animal study, CH-AgNP-CHF showed highest wound closure rate at 3rd, 5th, 7th, 14th and 21st day to indicate better and faster wound healing compared to marketed SilverKind® Nanofine gel, blank chitosan film and sterile gauze treated group (Control). Thus, CH-AgNP-CHF is more effective alternative for wound healing. Mixing is an important unit operation in monoclonal antibody (mAb) manufacturing. The goal is to achieve homogeneity without compromising product quality. Mixing-induced protein degradation and/or protein subvisible particle (SvP) formation, which impacts product quality, are associated with two common stress modes mechanical shear and air-liquid interfacial stress, which can generally be overcome by formulation optimization. This review addresses a unique stress mechanism that caused SvP formation when using certain bottom-mounted mixers (BMMs) equipped with impellers propelled by magnetic or mechanical coupling with a drive unit. During use, the coupling assembly is submerged in the protein solution allowing liquid access into the gap between the two bearings. Based on data from studies of BMMs and other small-scale mixers, grinding of the two bearings is a condition for inducing particulate formation. Although grinding stress is an accepted cause, identifying the responsible stress mechanism is challenging. By applying small-scale models, researchers attempted to elucidate the modes of stress, which ranged from common stress (mechanical shear; interfacial stress/adsorption; cavitation) to more speculative hypotheses (nucleation from nano- and micro-particles; localized thermal stress). Recent literature was reviewed, and recommendations are offered to development scientists and process engineers regarding mixer design to reduce protein SvP formation during mixing of mAb formulations. The aim of the present study was to investigate the effect of pullulan as additive to Eudragit® NM-L55 blend film for modification of the resulting film properties with regard to future drug release studies. Films of the plain polymers as well as of those of their blends at different ratios were prepared by an aqueous casting method. Infrared, mechanical, thermogravimetric, water vapor permeance and swelling index studies were performed with blend films of Eudragit® NM-L55 and pullulan. It was demonstrated that intermolecular interactions between Eudragit® NM-L55 and pullulan did not exist. An increasing fraction of up to 30 % pullulan in the Eudragit® NM-L55 blend film led to films with rising tensile strength, increasing Young’s modulus, and decreasing elongation at break. With increasing fraction of pullulan in the blend films, the thermal stability thereof decreased up to around 400 °C. Because of the high hydrophilicity of pullulan, the water vapor permeance increased with increasing fraction of pullulan in the blend films.

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