Management of rheumatoid arthritis (RA) requires long-term administration of different medications since there has been no cure until now. Etodolac (ETD) is a nonsteroidal anti-inflammatory drug commonly used for RA management. However, its long-term administration resulted in severe side effects. This study aimed to develop a transdermal in situ gel incorporating ETD-loaded polymeric nanoparticles (NPs) to target the affected joints for long-term management of RA. Several PLGA NPs incorporating 1% ETD were prepared by nanoprecipitation and optimized according to the central composite design. The optimum NPs (F1) exhibited 96.19 ± 2.31% EE, 282.3 ± 0.62 nm PS, 0.383 ± 0.04 PDI, and −6.44 ± 1.69 ZP. A hyaluronate coating was applied to F1 (H-F1) to target activated macrophages at inflammation sites. H-F1 exhibited 287.4 ± 4.2 nm PS, 0.267 ± 0.02 PDI, and −23.7 ± 3.77 ZP. Pluronic F-127 in situ gel (H-F1G) showed complete gelation at 29 °C within 5 min. ETD permeation from H-F1G was sustained over 48 h when applied to microporated skin and exhibited significant enhancement of all permeation parameters. Topical application of H-F1G (equivalent to 8 mg ETD) to Wistarrat microporated skin every 48 h resulted in antirheumatic therapeutic efficacy comparable to commercial oral tablets (10 mg/kg/day).

Background/Objectives: This study aimed to develop botanical nanofibers loaded with Psidium guajava leaf extract to heal wounds effectively. Methods: A 2³ factorial design was conducted to study the impact of freeze-drying parameters—freezing time, vacuum, and lyophilization time—on the total phenolic and flavonoid content in the lyophilized extract. Then, a polyurethane-based nanofiber dressing loaded with Psidium guajava leaf extract was fabricated using a one-step electrospinning technique. The nanofiber was evaluated considering total polyphenol and flavonoid content, surface roughness, and morphological assessment by scanning electron microscopy. Finally, the nanofiber was evaluated using in vivo wound-healing studies, histopathological analyses, and assessments of tissue levels of tumor necrosis factor-alpha, interleukin-6, matrix metalloproteinase, and growth factors. Results: The optimal conditions for freeze-drying the aqueous extract of Psidium guajava leaves were a freezing time of 24 h, a vacuum adjusted to 0.02 bar, and a lyophilization time of 48 h. The total polyphenol and flavonoid content within the nanofiber was 96 ± 1.2% and 91.83 ± 2.4%, respectively. Incorporating lyophilized extract in the nanofiber led to a decreased roughness average and root mean square roughness of the nanofiber. The nanofiber was continuous and had a smooth, uniform surface. The in vivo wound-healing assay showed superior wound-healing compared to the commercial Panthenol cream. These results were confirmed with histopathological studies. Conclusions: The extraction technique and lyophilization parameters significantly affect the bioactive content of Psidium guajava leaf extract. The botanical-loaded nanofiber showed greater wound-healing potential than a commercial cream, confirming its potential in regenerative medicine and wound repair applications.

Meptazinol is a centrally acting analgesic belonging to the hexahydro-azepine series, which has demonstrated mixed agonist and antagonist activity at opioid receptors.Receptor binding studies have shown that although meptazinol displays only a low affinity for µ and k opioid receptor sites, it has a some what higher affinity for the subpopulation of µ sites. These binding sites also displays a high affinity for the endogenous opioid peptides, and are thought to be responsible for, among other things, analgesia, but not for the mediation of respiratory depression. A component of its analgesic action is also attributable, in mice at least, to an effect on central cholinergic transmission. In this respect it differs from all conventional analgesic drugs which have been examined (1).Based on this information this drug requires no blocking of opioid receptor during the bioequivalence study. But to achieve the highest degree of safety, close monitoring will be performed to detect the occurrence of any side effect, As well as Anarchole 50mg tablets (Naltrexone, the opioid blocker) will be available at the emergency drugs store to treat any opioid side effect.