Polymeric nanoparticles (PNPs) represent a groundbreaking advancement in targeted drug delivery, offering significant benefits over conventional systems. This includes their versatility, biocompatibility, and ability to encapsulate diverse therapeutic agents and provide controlled release, improving efficacy while minimizing side effects. The polymers used in PNP formulations are critical, as they influence the nanoparticles’ physicochemical properties such as size, shape, surface charge, and drug-loading capacity. Recent developments in polymer chemistry and nanotechnology have led to the creation of smart PNPs that can respond to specific stimuli, enabling precise drug release in targeted environments. This review explores the mechanisms of drug delivery, innovations in polymeric formulations, and the fabrication and characterization techniques that enhance drug delivery systems. Additionally, it discusses challenges and future directions in the field, highlighting the potential for personalized medicine and the role of artificial intelligence in optimizing nanoparticle design. By examining the relationship between polymer characteristics and PNP performance, the review aims to promote innovative therapeutic strategies in modern medicine. Despite the promise of polymer-based drug delivery systems, challenges such as toxicity, stability, scalability, and regulatory compliance must be addressed. Future research should focus on rigorous testing, clear risk communication, and sustainable practices to support clinical translation and commercial viability. Overall, the integration of these elements is crucial for advancing PNPs in therapeutic applications.

The new health crises caused by SARS-CoV-2 have resulted in millions of deaths worldwide. First discovered in November 2021, the omicron variant is more transmissible and is able to evade the immune system better than other previously identified SARS-CoV-2 variants, leading to a spike in cases. Great efforts have been made to discover inhibitors against SARS-CoV-2. Main protease (M^pro) inhibitors are considered promising anti-SARS-CoV-2 agents. The U.S. FDA has issued an Emergency Use Authorization for ritonavir-boosted nirmatrelvir. Nirmatrelvir is the first orally bioavailable inhibitor of SARS-CoV-2 M^pro. There is an urgent need to monitor the mutations and solve the problem of resistance, especially omicron M^pro, which contains one mutation - P132H. In the present study, 132,57 phytochemicals from 80 medicinal plants grown in Saudi Arabia were docked into the active site of M^pro omicron variant. Free binding energies were also calculated. This led to the discovery of five phytochemicals that showed better docking scores than the bound ligand nirmatrelvir. In addition, these molecules exhibited favorable free binding energies. The stability of compounds 1-5 with the protein was studied using molecular dynamics (MD) simulations. These compounds showed acceptable ADMET properties. The results were compared with the wild type. These candidates could be envisioned as new hits against SARS-CoV-2. Communicated by Ramaswamy H. Sarma

Stroke is a critical global health issue characterized by sudden neurological dysfunction due to disrupted blood flow to the brain. This study aims to enhance understanding of stroke by examining its risk factors, symptoms, and prevention strategies. This was a cross-sectional study conducted in Saudi Arabia; the research involved a random sample of 442 participants over two months in 2024. The findings revealed that 63% of respondents were female, with the majority (64%) aged between 20-40 years, and 76% had university education. The overall knowledge level regarding stroke was moderate, at 62%. Of the 275 participants from the Northern Border Region, 60% demonstrated knowledge regarding risk factors, 58% regarding signs and symptoms, and 60% regarding treatment options. These results highlight a significant gap in knowledge among the Saudi public, particularly in understanding stroke's general aspects, risk factors, symptoms, and treatment options. The study emphasizes the importance of early recognition of stroke symptoms, summarized by the F.A.S.T. acronym, for timely medical intervention. It underscores the necessity for improved public education and awareness campaigns to enhance understanding and potentially reduce the impact of stroke in the community. A multifaceted approach integrating awareness, lifestyle modifications, and medical management is essential for effective stroke prevention and improved quality of life for individuals at risk.

Cytokine Release Syndrome (CRS) is a hyperinflammatory condition triggered by infections, immunotherapies, and systemic immune dysregulation. PANoptosis, a unique form of programmed inflammatory cell death that integrates pyroptosis, apoptosis, and necroptosis, has emerged as a key contributor to CRS pathogenesis. This review explores the mechanistic role of PANoptosis in CRS, with particular emphasis on immunotherapy-induced toxicity and viral infections such as SARS-CoV-2 and influenza. PANoptosis exacerbates cytokine storms through ZBP1, NLRP3, and CASP8-mediated pathways, creating a pathological feedback loop that intensifies inflammation and promotes multi-organ damage. Current evidence suggests that modulating PANoptotic pathways, including targeting TNF-α, IFN-γ, and inflammasome components, may mitigate cytokine-driven tissue injury. Despite growing interest, the therapeutic potential of PANoptosis remains underexplored. Advancing our understanding of PANoptosis and its interaction with cytokine signaling will be critical for developing effective interventions for CRS and improving outcomes in patients undergoing immunotherapy or battling severe infections.

The skin is the largest organ of the human body and acts as a major protective barrier against external agents. However, the highly organized stratum corneum limits the effective delivery of many therapeutic compounds, especially hydrophilic and high-molecular-weight drugs. Conventional topical formulations often exhibit poor permeability, low bioavailability, and limited targeting efficiency. This review discusses recent advances in nanotechnology-based drug delivery systems, including bio-based, biodegradable, and biocompatible polymeric nanocarriers for dermal and transdermal applications, with particular emphasis on vesicular, polymeric, and hybrid nanosystems. Nanocarriers such as liposomes, ethosomes, transfersomes, polymeric nanoparticles, micelles, nanogels, and lipid–polymer hybrid systems have demonstrated improved drug solubility, stability, controlled release, and skin permeation for localized (dermal) delivery compared with conventional formulations. In addition, biodegradable polymeric materials enhance dermal deposition and prolong drug retention, leading to improved therapeutic efficacy. These nanosystems can facilitate enhanced transdermal drug transport under optimized conditions; however, the extent of systemic delivery varies widely depending on drug physicochemical properties, formulation characteristics, and application conditions. Drug transport may occur through intercellular, transcellular, and follicular pathways, resulting in enhanced bioavailability and site-specific delivery. Claims regarding transdermal (systemic) absorption are restricted to cases supported by in vivo or clinical evidence. Furthermore, combining nanocarriers with microneedles and stimuli-responsive platforms has expanded the potential for controlled and on-demand transdermal delivery. Recent preclinical and clinical studies have reported that nanocarrier-based methotrexate gels reduced PASI-like scores by over 70% in psoriatic models, while oleic acid vesicle formulations achieved more than 95% cure rates in rodent models of tinea corporis. Despite these advances, challenges related to large-scale production, stability, regulatory approval, and clinical translation remain significant. Future developments integrating smart nanocarriers, bio-based polymeric biomaterials, wearable technologies, and AI-assisted design may improve personalized dermatological therapies. These innovations in nanocarrier drug delivery are accelerating the translation of advanced therapies to the clinic, promising safer, more effective and personalized dermatological treatments.