"Employment of PEGylated ultra-deformable transferosomes for transdermal delivery of tapentadol with boosted bioavailability and analgesic activity in post-surgical pain".

The utilization of the proper and safe analgesics was considered a major concern in pain alleviation especially that associated with surgical procedures. Novel analgesics as Tapentadol hydrochloride (TAP) was involved efficiently instead of the common opioids to overcome the subsequent severe and common adverse effects associated with opioids utilization. Unfortunately, the extensive first pass metabolism limits the oral bioavailability of TAP and predisposes to a diminished duration of action, hence larger frequent doses of TAP will be required. Therefore, the target of this study was to lodge TAP into PEGylated transferosomes to boost its transdermal delivery. The PEGylation contemplated to boost both TAP permeability and bioavailability besides offering extra resilience to the vesicles. The impact of diverse variables on the characteristics of the vesicles and distinguishing the optimal formula were implemented adopting 23 factorial experiment via Design Expert® software. The resulted eight formulae were fabricated by thin film hydration technique, additionally they were evaluated based on the findings of entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and the optimal one was involved in further assessments. The optimal formula (F8) exhibited spherical vesicles with EE% of 77.9 ± 3.4 %, PS of 150.5 ± 5.33 nm, PDI of 0.47 ± 0.05, ZP of -40.7 ± 4.6 mV and it also revealed greater deformability index (30.9 ± 6.1 g) relative to traditional transferosomes (12.15 ± 2.49 g). In addition, confocal laser scanning microscopy examination affirmed the superior penetration of Rhodamine B (RhB) dye thorough the rat's skin from F8 relative to the dye solution. The safety of F8 was confirmed by histopathological study. Moreover, dermato-kinetic study disclosed that TAP exhibited higher retention within the rat's skin form F8 relative to TAP dispersion. Furthermore, the in vivo pharmacodynamics activities conducted on male rats confirmed the superiority of F8 over the drug dispersion in alleviation the induced pain by IP injection of acetic acid and by formation of paw incisions. Collectively, the credibility of F8 as panel for transdermal delivery of TAP with boosted bioavailability and analgesic activity could be ensured on the basis of the obtained findings.

Hemophagocytic Lymphohistiocytosis in the Elderly.

Hemophagocytic lymphohistiocytosis (HLH) is a rare disease of massive, dysregulated cytokine release and secondary multiorgan failure and is associated with high mortality. Primary HLH occurs predominately in infants and young children with a genetic predisposition. Acquired HLH is less well characterized and usually occurs in younger adults in the setting of severe inflammation triggered by infection or malignancy. Little is known about the disease in elderly. We report 3 patients >50 years old who presented with multiorgan failure and shock without an identifiable source and were ultimately diagnosed with acquired HLH. We performed a literature review of HLH in adults >50 years of age and identified an additional 68 cases. Mean age was 62 years, with male predominance. Most cases were triggered by infection (49%) followed by malignancy (27%). Nineteen patients were treated with the HLH-94 protocol, 11 received corticosteroids and the remainder received non-HLH specific interventions. Overall mortality was 62%.