Ahmed Elshafeey

Carvedilol (CV), a β-blocker essential for treating cardiovascular diseases, faces bioavailability challenges due to poor water solubility and first-pass metabolism. This study developed and optimized chitosan (CS)-coated niosomes loaded with CV (CS/CV-NS) for intranasal (IN) delivery, aiming to enhance systemic bioavailability. Utilizing a Quality-by-Design (QbD) approach, the study investigated the effects of formulation variables, such as surfactant type, surfactant-to-cholesterol (CHOL) ratio, and CS concentration, on CS/CV-NS properties. The focus was to optimize specific characteristics including particle size (PS), polydispersity index (PDI), zeta potential (ZP), entrapment efficiency (EE%), and mucin binding efficiency (MBE%). The optimal formulation (Opt CS/CV-NS), achieved with a surfactant: CHOL ratio of 0.918 and a CS concentration of 0.062 g/100 mL, using Span 60 as the surfactant, exhibited a PS of 305 nm, PDI of 0.36, ZP of + 33 mV, EE% of 63 %, and MBE% of 57 %. Opt CS/CV-NS was characterized for its morphological and physicochemical properties, evaluated for stability under different storage conditions, and assessed for in vitro drug release profile. Opt CS/CV-NS demonstrated a 1.7-fold and 4.8-fold increase in in vitro CV release after 24 h, compared to uncoated CV-loaded niosomes (Opt CV-NS) and free CV, respectively. In vivo pharmacokinetic (PK) study, using a rat model, demonstrated that Opt CS/CV-NS achieved faster Tmax and higher Cmax compared to free CV suspension indicating enhanced absorption rate. Additionally, Opt CV-NS showed a 1.68-fold higher bioavailability compared to the control. These results underscore the potential of niosomal formulations in enhancing IN delivery of CV, offering an effective strategy for improving drug bioavailability and therapeutic efficacy. © 2024 Elsevier B.V.

The current medical practice in treating Hepatocellular carcinoma (HCC) using Drug Eluting Transarterial chemoembolization (DEB-TACE) technique is limited only to hydrophilic ionizable drugs, that can be attached ionically to the oppositely charged beads. This limitation has forced physicians to subscribe the more hydrophobic, first treatment option drugs, like sorafenib systemically via the oral route, thus flooding the patient system with a very powerful, non-specific, multiple-receptor tyrosine kinase inhibitor that is associated with notorious side effects. In this paper, a new modality is introduced, where highly charged, drug loaded liposomes are added to oppositely charged DEBs in a manner causing them to “explode” and the drug is eventually attached to the beads in the lipid patches covering their surfaces; therefore we call them “Explosomes”. After fully describing the preparation process and in vitro characterization, this manuscript delves into an in vivo pharmacokinetic study over 50 New Zealand rabbits, where explosomal loading is challenged vs oral as well as current practice of emulsifying sorafenib in lipiodol. Over 14 days of follow up, and compared to other groups, explosomal loading of SRF on embolic beads proved to cause a slower release pattern with longer Tmax, lower Cmax and less washout to general circulation in healthy animals. This treatment modality opens a new untapped door for local sustained delivery of hydrophobic drugs in catheterized organs. © 2023 Elsevier B.V.

The aim of this study was to evaluate the bioavailability of two aripiprazole tablets, coprecipitate (CP) and nanoparticles (NP) when compared to the market tablets. A single-dose, randomized, three period crossover design under fasting conditions in healthy human volunteers was studied. The dissolution rate of the CP, NP and market tablets was determined. In order to investigate the feasibility of in vitro data as a tool for predicting in vivo results, two types of in vitro-in vivo correlation (IVIVC), level C and multiple level C, were studied. Almost 75% of aripiprazole was dissolved from the nanoparticles tablets within 10 minutes compared with 20% and 46% for coprecipitate and market tablets, respectively. The mean AUC 0-72 value of aripiprazole from the NP tablets (6136.35 ± 421.29 ng.hr/mL) was significantly higher than both CP tablets (3216.12 ± 525.02 ng.hr/mL) and market tablets (5215.57 ± 457.28 ng.hr/mL) (p d" 0.05). The relative bioavailability of aripiprazole after oral administration of the CP and NP tablets was 61.66% and 117.65%, respectively. The higher dissolution rate of NP tablets resulted in rapid absorption of aripiprazole and consequently higher bioavailability. Multiple level C IVIVC showed the bioequivalence of NP and bioinequivalence of the CP tablets in comparison to market tablets.