Promising Adjunct Medicines in the Protocol of COVID-19 Clinical Trial.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative organism of COVID-19. Since this disease is considered new and does not have an approved curative protocol, many researchers have tackled the possible options for COVID-19 prevention and therapeutic approaches. We address herein the phenomena of cytokine storm (the main cause of death) associating with the late stage of COVID19. Cytokine storm is undertaken in an attempt to provide information about its possible underlying causes, and to clarify some points that can be of value in guiding treatment practices for a clinical trial.

Electron microscopy overview of SARS-COV2 and its clinical impact.

Research centers around the world are competing to develop therapeutic and prophylactic agents to provide new intervention strategies that could halt or even help slow the progression of the COVID19 pandemic. This requires a deep understanding of the biology and cytopathology of the interaction of SARS-CoV-2 with the cell. This review highlights the importance of electron microscopy (EM) in better understanding the morphology, the subcellular morphogenesis, and pathogenesis of SARS-CoV-2, given its nanometric dimensions. The study also underscores the value of cryo-electron microscopy for analyzing the structure of viral protein complex at atomic resolution in its native state and the development of novel antibodies, vaccines, and therapies targeting the trimeric S spike proteins and the viral replication organelles. This review highlighted the emergence in a short period of time of several viral variants of concern with enhanced transmissibility and increased infectivity. This is due to the elevated affinity of the host receptor with acquired adaptive mutations in the spike protein gene of the virus.Subsequently, to the technical improvement of EM resolutions and the recent promising results with SARS-CoV2 variant structure determination, antibodies production, and vaccine development, it is necessary to maximize our investigations regarding the potential occurrence of immune pressure and viral adaptation secondary to repeated infection and vaccination.

Exploiting bilosomes for delivering bioactive polysaccharide isolated from Enteromorpha intestinalis for hacking hepatocellular carcinoma.

Bile salts containing vesicles (bilosomes) represent a portentous vesicular carrier that showed prosperous results in delivering active moieties in the gastrointestinal tract (GIT). In this study, bilosomes were exploited to deliver sulfated polysaccharide-protein complexes of Enteromorpha intestinalis (EHEM) and enhance its activity against hepatocellular carcinoma as well as resist harsh GIT conditions. Bilosomes were prepared using the sodium salt of three different bile acids (cholic, deoxycholic, taurodeoxycholic) and two different nonionic surfactants (Span 40 and 65). The effects of experimental variables were thoroughly studied to obtain an optimum formulation loading EHEM. The selected formulation (EH-Bilo-2) prepared with sodium cholate and Span 65 displayed nano-sized (181.1 ± 16.80 nm) spherical vesicles with reasonable entrapment efficiency (71.60 ± 0.25%) and controlled release properties; and thus was investigated as anti-hepatocarcinogenic candidate for in vivo studies. Treatment of hepatocellular carcinoma (HCC) bearing rats with EH-Bilo-2 experienced significant decrease in serum α-fetoprotein, endoglin, lipocalin-2, and heat shock protein 70 levels vs. the untreated counterparts. Furthermore, the photomicrographs of their liver tissue sections showed focal area of degenerated pleomorphic hepatocytes with fine fibrosis originating from the portal area. Thus, the optimized bilosomal formulation is a promising delegate for tackling hepatocellular carcinoma owing to its powerful anti-cancer and anti-angiogenic activity.

Enhanced oral bioavailability and sustained delivery of glimepiride via niosomal encapsulation: in-vitro characterization and in-vivo evaluation.

This study was designed to investigate the potency of niosomes, for glimepiride (GLM) encapsulation, aiming at enhancing its oral bioavailability and hypoglycemic efficacy. Niosomes containing nonionic surfactants (NIS) were prepared by thin film hydration technique and characterized. In-vitro release study was performed using a dialysis technique. In-vivo pharmacodynamic studies, as well as pharmacokinetic evaluation were performed on alloxan-induced diabetic rats. GLM niosomes exhibited high-entrapment efficiency percentages (E.E. %) up to 98.70% and a particle size diameter ranging from 186.8 ± 18.69 to 797.7 ± 12.45 nm, with negatively charged zeta potential (ZP). Different GLM niosomal formulation showed retarded in vitro release, compared to free drug. In-vivo studies revealed the superiority of GLM niosomes in lowering blood glucose level (BGL) and in maintaining a therapeutic level of GLM for a longer period of time, as compared to free drug and market product. There was no significant difference between mean plasma AUC0-48 hr of GLM-loaded niosomes and that of market product. GLM-loaded niosomes exhibited seven-fold enhancement in relative bioavailability in comparison with free drug. These findings reinforce the potential use of niosomes for enhancing the oral bioavailability and prolonged delivery of GLM via oral administration.

Enhancement of the topical tolnaftate delivery for the treatment of tinea pedis via provesicular gel systems.

Tolnaftate is a thiocarbamate antifungal drug which is therapeutically active against dermatophytes that cause various forms of tinea. Due to the small amount of tolnaftate released from ordinary ointment bases and insufficient penetration through the infected skin layers the need to incorporate the drug in a more suitable pharmaceutical form has evolved. A provesicular system is one such form that can solve these problems. Once in contact with the skin, dilution with moisture occurs and the provesicular system rapidly transforms into a vesicular one. Provesicular systems were prepared according to full-factorial experimental design. Plain provesicular systems were compared with systems containing Phospholipon 80 H and Lipoid S45 as penetration enhancers. Design expert software was used to analyze the effect of formulation variables (type of Span used as well as the presence or the absence of the penetration enhancer and its type) on the dependent variables: percent encapsulation efficiency (EE%), vesicle size and percent in vitro drug released). Three formulations were chosen; a plain provesicular system (PV-2), one containing Phospholipon 80H (PV-6) and another containing Lipoid S45 (PV-10) with the goal to reveal the effect of penetration enhancer on morphology, rheological properties and ex vivo permeation using confocal laser scanning microscopy (CLSM). Analysis of CLSM results showed that the penetration enhancing effect for the tested formulations followed the order PV-10 > PV-6 > PV-2. Promising clinically active treatment for tinea patients could be expected as shown by the in vivo permeation results for the provesicular systems as suggested by the CLSM results.