Cubogel as potential platform for glaucoma management.

The aim of this work is to survey the potential of cubogel as an ocular dosage form to boost the corneal permeability of Dorzolamide Hydrochloride DZ; an antiglaucomal drug. DZ-loaded cubosomal dispersions were prepared according to Box-Behnken design, where the effect of independent variables; Monoolein MO concentration (2.5, 5 and 7.5%w/w), Pluronic® F127 concentration (0.25, 0.5 and 0.75%w/w) and magnetic stirrer speed of (400, 800 and 1200 rpm) was studied on PS (nm), Zp (-mV) and Q 2 h (%) respectively. The prepared formulae were characterized via drug content DC (%), particle size PS (nm), polydispersity index PDI, zeta potential Zp (-mV), in-vitro drug release (Q 2 h%) and finally TEM. The optimized formulation composed of: 6.13% w/w of MO, 0.75% w/w of F127 and prepared at 1200 rpm stirring speed was chosen based on the criteria of minimum PS (nm), maximum Zp (-mV) and minimum Q 2 h (%). Results revealed that the optimum formula showed PS of 153.3 ± 8.4 n, Zp of 32 ± 3 -mV and 37.78 ± 1.3% released after 2 h. Carbopol 934 (1% w/v) as gelling agent was used to prepare the optimum cubogel, which was further evaluated by DSC, ex-vivo permeation and stability studies at 4 °C for three months. Moreover, in vivo studies of the optimized cubogel include; draize test, histological examination, confocal laser scanning microscopy (CLSM) and intraocular pressure (IOP) measurement. Results revealed that the optimized cubogel was considerably safe, stable and competent to corneal delivery as assured by draize and histological examination. CLSM showed a deeper penetration of more than 2.5-fold. A higher bioavailability (288.24 mg. h/ml) was attained from cubogel compared to the market product Trusopt® eye drops (115.40 mg. h/ml) following IOP measurement. Therefore, DZ-loaded cubogel could be considered as promising delivery system to boost the transcorneal permeation hence corneal bioavailability of DZ as antiglaucomal drug.

Therapeutic effect of mesenchymal stem cells on histopathological, immunohistochemical, and molecular analysis in second-grade burn model.

BACKGROUND AND AIM: Deleterious cutaneous tissue damages could result from exposure to thermal trauma, which could be ameliorated structurally and functionally through therapy via the most multipotent progenitor bone marrow mesenchymal stem cells (BM-MSCs). This study aimed to induce burns and examine the effect of BM-MSCs during a short and long period of therapy. MATERIAL AND METHODS: Ninety albino rats were divided into three groups: group I (control); group II (burn model), the animals were exposed to the preheated aluminum bar at 100°C for 15 s; and group III (the burned animals subcutaneously injected with BM-MSCs (2×106 cells/ ml)); they were clinically observed and sacrificed at different short and long time intervals, and skin samples were collected for histopathological and immunohistochemical examination and analysis of different wound healing mediators via quantitative polymerase chain reaction (qPCR). RESULTS: Subcutaneous injection of BM-MSCs resulted in the decrease of the wound contraction rate; the wound having a pinpoint appearance and regular arrangement of the epidermal layer with thin stratum corneum; decrease in the area percentages of ADAMs10 expression; significant downregulation of transforming growth factor-ß (TGF-ß), interleukin-6 (IL-6), tumor necrotic factor-α (TNF-α), metalloproteinase-9 (MMP-9), and microRNA-21; and marked upregulation of heat shock protein-90α (HSP-90α) especially in late stages. CONCLUSION: BM-MSCs exhibited a powerful healing property through regulating the mediators of wound healing and restoring the normal skin structures, reducing the scar formation and the wound size.

Up-regulation of TLR-4 in the brain after ischemic kidney-induced encephalopathy in the rat.

Ischemic acute kidney injury (AKI) is usually accompanied by neuroinflammation-induced encephalopathy. However, the specific mechanism remains unclear. Toll-like receptors (TLR), specifically TLR-4 has been linked to ischemic reperfusion injury in different organs like kidney, brain and liver. Here, we induced an ischemic reperfusion kidney injury in Sprague Dawley rats. All animals were evaluated using behavioral tests which revealed locomotor activity and motor disturbances in the AKI group. The brains were then examined by immunostaining with ionized calcium binding adaptor molecule 1 (microglial marker) and TLR-4 antibodies. The histological analysis revealed significant up-regulation of TLR-4 in the hippocampus and striatum in the AKI group. These data demonstrate for the first time, the triggering effect of TLR-4 on AKI-induced neuroinflammation in the brain that may lead to AKI-induced encephalopathy. This would also generate a novel hypothesis that using TLR blockers may have a role in preventing AKI effects on the brain.

Immunohistochemical study of osteopontin, Ki-67, and CD34 of psoriasis in Mansoura, Egypt.

BACKGROUND AND OBJECTIVE: Psoriasis is a chronic inflammatory skin disease characterized by hyper-proliferation, abnormal differentiation, and inflammatory infiltration in epidermis and dermis. We planned this study to analyze probable associations between Osteopontin (OPN), Ki-67, CD34, and histopathological features in psoriasis. MATERIALS AND METHODS: We studied OPN expression and its correlation with Ki-67 and CD34 expression in lesional, non-lesional skin, and normal skin. Immunoreactivity for OPN and Ki-67 was based on the level of epidermal staining. CD34 expression was scored as mild, moderate, and strong, according to the number of stained dermal capillaries. RESULTS: Our results showed statistically significant differences in the expression of OPN, Ki-67, and CD34 between lesional and non-lesional skin as well as between non-lesional skin and control group (P ≤ 0.001). In addition, there was a significant difference in the expression of OPN, Ki-67, and CD34 between control and lesional group (P=0.02, P=0.02, and P=0.04, respectively). CONCLUSIONS: OPN expression seems to be related to Ki-67 (proliferation index) and CD34 expression (angiogenesis marker) confirming its role in the pathogenesis of psoriasis. Then "anti- OPN and anti-angiogenesis" may eventually become a useful therapeutic approach in psoriasis.

Colon-targeted celecoxib-loaded Eudragit® S100-coated poly-ε-caprolactone microparticles: preparation, characterization and in vivo evaluation in rats.

CONTEXT: Celecoxib suffers from low and variable bioavailability following oral administration of solutions or capsules. Recent studies proved that chemoprevention of colorectal cancer is possible with celecoxib. OBJECTIVE: This work aimed to tailor colon-targeted celecoxib-loaded microparticles using time-dependant and pH-dependant coats. Estimation of drug pharmacokinetics following oral administration to fasted rats was another goal. METHODS: A 2³ factorial design was adopted to develop poly-ε-caprolactone (PCL) celecoxib-loaded microparticles (F1-F8). To minimize drug-percentages released before colon, another coat of Eudragit® S100 was applied. In vitro characterization of microparticles involved topography, determination of particle size and entrapment efficiency (EE %). Time for 50% drug release (t(50%)) and drug-percentages released after 2 hours (Q(2h)) and 4 hours (Q(4h)) were statistically compared. Estimation of drug pharmacokinetics following oral administration of double-coat microparticles (F10) was studied in rats. RESULTS: PCL-single-coat microparticles were spherical, discrete with a size range of 60.66 ± 4.21-277.20 ± 6.10 µm. Direct correlations were observed between surfactant concentration and EE%, Q(2h) and Q(4h). The PCL M.wt. and drug: PCL ratio had positive influences on EE% and negative impacts on Q(2h) and Q(4h). When compared to the best achieved PCL-single-coat microparticles (F2), the double-coat microparticles (F10) showed satisfactory drug protection; Q(2h) and Q(4h) were significantly (P < 0.01) decreased from 31.84 ± 1.98% and 54.72 ± 2.10% to 15.92 ± 1.78% and 26.93 ± 2.76%, respectively. When compared to celecoxib powder, F10 microparticles enhanced the bioavailability and extended the duration of drug-plasma concentration in rats. CONCLUSION: The developed double-coat microparticles could be considered as a promising celecoxib extended-release colon-targeting system.