Preparation and In Vitro/In Vivo Characterization of Porous Sublingual Tablets Containing Ternary Kneaded Solid System of Vinpocetine with β-Cyclodextrin and Hydroxy Acid

The demand for sublingual tablets has been growing during the previous decades especially for drugs with extensive hepatic first-pass metabolism. Vinpocetine, a widely used neurotropic agent, has low oral bioavailability due to its poor aqueous solubility and marked first-pass metabolism. Accordingly, the aim of this work was to develop tablets for the sublingual delivery of vinpocetine. Initially, the feasibility of improving vinpocetine’s poor aqueous solubility by preparing kneaded solid systems of the drug with β-Cyclodextrin and hydroxy acids (citric acid and tartaric acid) was assessed. The solid system with improved solubility and dissolution properties was incorporated into porous tablets that rapidly disintegrate permitting fast release of vinpocetine into the sublingual cavity. The pores were induced into these tablets by directly compressing the tablets’ excipients with a sublimable material, either camphor or menthol, which was eventually sublimated leaving pores. The obtained results demonstrated that the tablets prepared using camphor attained sufficient mechanical strength for practical use together with rapid disintegration and dissolution. In vivo absorption study performed in rabbits indicated that the sublingual administration of the proposed porous tablets containing vinpocetine solid system with β-Cyclodextrin and tartaric acid could be useful for therapeutic application

Activator Protein-1 Transcriptional Activity Drives Soluble Micrograft-Mediated Cell Migration and Promotes the Matrix Remodeling Machinery

Impaired wound healing and tissue regeneration have severe consequences on the patient's quality of life. Micrograft therapies are emerging as promising and affordable alternatives to improve skin regeneration by enhancing the endogenous wound repair processes. However, the molecular mechanisms underpinning the beneficial effects of the micrograft treatments remain largely unknown. In this study, we identified the active protein-1 (AP-1) member Fos-related antigen-1 (Fra-1) to play a central role in the extracellular signal-regulated kinase- (ERK-) mediated enhanced cell migratory capacity of soluble micrograft-treated mouse adult fibroblasts and in the human keratinocyte cell model. Accordingly, we show that increased micrograft-dependent in vitro cell migration and matrix metalloprotease activity is abolished upon inhibition of AP-1. Furthermore, soluble micrograft treatment leads to increased expression and posttranslational phosphorylation of Fra-1 and c-Jun, resulting in the upregulation of wound healing-associated genes mainly involved in the regulation of cell migration. Collectively, our work provides insights into the molecular mechanisms behind the cell-free micrograft treatment, which might contribute to future advances in wound repair therapies

Transition Economies in the Middle East: the Syrian Experience

There have been no in depth studies of post Socialist transition in the Middle East. Syria’s experience is a useful one to explore given its historically important role in the region and its distinctive characteristics. The Syrian economic transition, from the early 1990s to 2011, was in two phases: an incremental liberalisation phase and a transition to Social Market Economy phase. During both phases, Syrian policy makers showed a preference for a gradualist approach to economic transition, rather than a big-bang approach. This was facilitated by oil revenues and subsidies from the Gulf States. The Syrian experience therefore has its own distinct characteristics, as well as elements in common with the transitions in other post Socialist economies

EFFECT OF LOW ENERGY VERSUS MEDIUM ENERGY RADIAL SHOCK WAVE THERAPY IN THE TREATMENT OF CHRONIC PLANTER FASCIITIS

Background: Plantar fasciitis (PF) is the most common cause of heel pain and it can often be a challenge for clinicians to treat successfully. Radial shock wave therapy (RSWT) has been introduced recently for treatment of musculoskeletal disorders. Different energy levels of shock wave therapy have been used in the literatures for treatment of PF with no clear settled parameters. Therefore, the purpose of this study was intended to investigate and compare the efficacy of two different energy levels of RSWT on PF patients. Methods: Forty patients having unilateral chronic PF were recruited for the study from orthopedic outpatient clinics of Cairo University hospitals and National Institute of Neuromotor System Cairo Egypt, with a mean age of (47.15±4.57) years. Patients were randomly assigned into two equal groups. Group (A) treated with low intensity level of 1.6 bars (0.16 mJ/mm2) RSWT and group (B) treated with medium intensity level of 4 bars (0.38 mJ/mm2) RSWT. Functional assessment of the foot based on Foot Function Index (FFI) and Present pain intensity was measured during rest by Visual Analogue Scale (VAS). Results: There was as significant decreased in the total FFI scores from (118.42 ±6.51) to (81.37 ±3.46) for group (A) and from (118.93 ±6.85) to (58.50 ±3.22) for group (B). Also regarding VAS Scores there was as significant decreased in the pain intensity from (5.11 ±0.41) to (2.85 ±0.31) for group (A) and from (4.95 ±0.39) to (2.05 ±0.22) for group (B). Conclusion: Radial shock wave therapy is an effective modality that should be considered in the treatment of chronic PF, while the medium energy level RSWT is better than the low energy level RSWT in regarding to the measured treatment outcomes

Studying the influence of formulation and process variables on Vancomycin-loaded polymeric nanoparticles as potential carrier for enhanced ophthalmic delivery

Ocular topically applied Vancomycin (VCM) suffers poor bioavailability due to its high molecular weight and hydrophilicity. In the Present investigation, VCM-loaded polymeric nanoparticles (PNPs) were developed aiming to enhance its ocular bioavailability through prolonging its release pattern and ophthalmic residence. PNPs were prepared utilizing double emulsion (W/O/O), solvent evaporation technique. 2 3X4 1 full factorial design was applied to evaluate individual and combined influences of polymer type, Eudragit® RS100, sonication time, and Span® 80 concentration on PNPs particle size, encapsulation efficiency, and zeta potential. Further, the optimized formulae were incorporated in 1% Carbopol® - based gel. In-vivo evaluation of the optimized formulae was performed via Draize test followed by microbiological susceptibility testing on albino rabbits. Results revealed successful formulation of VCM- loaded PNPs was achieved with particle sizes reaching 155 nm and up to 88% encapsulation. Draize test confirmed the optimized formulae as non-irritating and safe for ophthalmic administration. Microbiological susceptibility testing confirmed prolonged residence, higher Cmax. with more than two folds increment in the AUC(0.25- 24) of VCM-PNPs over control groups. Thus, VCMloaded PNPs represent promising carriers with superior achievements for enhanced Vancomycin ophthalmic delivery over the traditional use of commercially available VCM parenteral powder after constitution into a solution by the ophthalmologists