Current Pharmaceutical Design - Volume 31, Issue 36, 2025

Gastrointestinal (GI) cancers, including gastric cancer, are among the most common and deadly cancers worldwide. Patients diagnosed with GI cancer still have a poor prognosis, largely resulting from the late stage of presentation for most of these patients and resistance to conventional therapy. This review covers new therapeutic strategies that apply advances in nanotechnology, immunotherapy, and drug delivery to overcome these challenges. Polymeric and metallic nanoparticles are distinguished for their potential to improve drug stability and solubility, as well as targeting drugs, thus diminishing systemic toxicity. The review centers around the use of immunotherapy in immune checkpoint inhibitors, CAR-T cell therapy, as well as the use of cancer vaccines to re-orient the immune system to be effective against cancer cells. Oncolytic viral therapy and bacteria-based treatments are unique non-conventional approaches that have a potential synergistic impact when used in concomitance with traditional methods. This review presents one of the most promising drug delivery systems: liposomes and micelles that can enhance pharmacokinetics and improve therapeutic results with controlled and site-specific release of anticancer agents. This review critically analyzes the strengths and challenges that include bioavailability, toxicity, and clinical translation, along with strategies to overcome such barriers. The review presents the most salient evidence to date and demonstrates the transformative potential of combining nanotechnology with immunotherapeutic and targeted treatments for managing gastric and other GI cancers. Future research should be focused on optimizing these platforms for clinical applications for the betterment of patient outcomes around the globe.

Nanoemulsions (NEs) are submicron-sized colloidal dispersions (20–500 nm) consisting of oil and aqueous phases stabilized by surfactants and cosurfactants. Despite their thermodynamic instability, NEs maintain kinetic stability, preventing separation and aggregation. This stability distinguishes them from microemulsions, which are thermodynamically stable and formed spontaneously. The emulsification process involves a reduction in Gibbs surface free energy facilitated by emulsifiers that lower interfacial tension, crucial for compensating for the high surface area associated with small droplet sizes. The Gibbs free energy reduction is vital as it helps in stabilizing nanoemulsions, while Laplace pressure, resulting from the curvature of the droplets, affects the stability and uniformity of the system. High Laplace pressures in smaller droplets can lead to coalescence, but the proper formulation with suitable surfactants can help mitigate this effect. This review investigates the hypothesis that NEs can significantly enhance the solubility and bioavailability of hydrophobic drugs by optimizing their formulation and stability. We focus on the role of emulsification techniques in creating stable nanoemulsions, with particular attention to the impact of hydrophilic-lipophilic balance (HLB) and critical packing parameters (CPP) on droplet size and stability. Furthermore, we provide a detailed comparison of various preparation methods, including ultrasonication and high-pressure homogenization, emphasizing their influence on droplet size, stability, and scalability. Experimental data from in vitro and in vivo studies illustrate the advantages of NEs for oral drug delivery, with findings showing significant improvements in bioavailability for poorly soluble drugs, such as paclitaxel and curcumin, under optimized formulation conditions. This review highlights the potential of NEs to overcome the limitations of traditional drug delivery systems and provides a roadmap for future research to improve their commercial viability and therapeutic outcomes.

Chronic lymphocytic leukemia (CLL) constitutes a heterogeneous hematological malignancy, often correlated with disruptions in various signaling pathways, chromosomal deletions, and gene mutations. A comprehensive grasp of CLL pathogenesis and its associated risk factors remains vital for the development of more efficacious treatment strategies. Although non-coding RNAs (ncRNAs) do not encode proteins, they possess substantial regulatory influence over target genes. These ncRNAs govern a multitude of target genes implicated in the pathogenesis of CLL. Furthermore, some ncRNAs serve as prognostic markers in CLL and might contribute to overcoming chemotherapy resistance. This review determines the association between ncRNAs and the molecular mechanisms driving the onset and advancement of CLL, with particular emphasis on the roles of these ncRNAs in modulating signaling pathways, encompassing NF-κB/PI3K-AKT/TNF and P53 in CLL. It also underscores their relevance as significant biomarkers and their potential as therapeutic targets in clinical CLL settings.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, affecting about a quarter of the world's population. As the prevalence of obesity and metabolic syndrome rises, NAFLD is projected to become the leading cause of cirrhosis in the coming years. NAFLD is a complex disease whose pathophysiology mainly focuses on metabolic dysfunction and intestinal microecological dysregulation. Shifts between free fatty acid (FFA) metabolism and cell damage could be of major interest in finding new therapeutic targets. However, current public understanding of these diseases remains limited. Based on bibliometrics and extensive studies, this study explored the mechanisms by which FFAs regulate the occurrence of NAFLD. This review not only focuses on the role of the vicious cycle derived from FFA metabolic disorders, ecological disorders, and liver damage immunity concerning diabetes mellitus type 2 and NAFLD but also discusses the mechanisms involved in them.