Exosomes are cell-derived, nano-sized extracellular vesicles comprising a lipid bilayer membrane that encapsulates several biological components, such as nucleic acids, lipids, and proteins. The role of exosomes in cell–cell communication and cargo transport has made them promising candidates in drug delivery for an array of diseases. Despite several research and review papers describing the salient features of exosomes as nanocarriers for drug delivery, there are no FDA-approved commercial therapeutics based on exosomes. Several fundamental challenges, such as the large-scale production and reproducibility of batches, have hindered the bench-to-bedside translation of exosomes. In fact, compatibility and poor drug loading sabotage the possibility of delivering several drug molecules. This review provides an overview of the challenges and summarizes the potential solutions/approaches to facilitate the clinical development of exosomal nanocarriers.

The current 5-year survival rate of pancreatic cancer is about 12%, making it one of the deadliest malignancies. The rapid metastasis, acquired drug resistance, and poor patient prognosis necessitate better therapeutic strategies for pancreatic ductal adenocarcinoma (PDAC). Multiple studies show that combining chemotherapeutics for solid tumors has been successful. Targeting two distinct emerging hallmarks, such as non-mutational epigenetic changes by panobinostat (Pan) and delayed cell cycle progression by abemaciclib (Abe), inhibits pancreatic cancer growth. HDAC and CDK4/6 inhibitors are effective but are prone to drug resistance and failure as single agents. Therefore, we hypothesized that combining Abe and Pan could synergistically and lethally affect PDAC survival and proliferation. Multiple cell-based assays, enzymatic activity experiments, and flow cytometry experiments were performed to determine the effects of Abe, Pan, and their combination on PDAC cells and human dermal fibroblasts. Western blotting was used to determine the expression of cell cycle, epigenetic, and apoptosis markers. The Abe-Pan combination exhibited excellent efficacy and produced synergistic effects, altering the expression of cell cycle proteins and epigenetic markers. Pan, alone and in combination with Abe, caused apoptosis in pancreatic cancer cells. Abe-Pan co-treatment showed relative safety in normal human dermal fibroblasts. Our novel combination treatment of Abe and Pan shows synergistic effects on PDAC cells. The combination induces apoptosis, shows relative safety, and merits further investigation due to its therapeutic potential in the treatment of PDAC.

Vulvovaginal candidiasis (VVC) is a common mucosal infection that predominantly affects reproductive-aged women. Although conventional antifungal agents remain the primary treatment option, there is growing interest in developing alternative therapeutic approaches that can enhance antifungal efficacy while potentially reducing treatment burden. Natural products have emerged as valuable sources of bioactive compounds with antifungal potential, offering opportunities for novel combination-based therapies. Ebselen (EB), an organoselenium compound with potent redox-modulating and antifungal properties, and its structurally related analogs represent promising candidates for such strategies. Likewise, black seed oil (BSO), derived from Nigella sativa, and its major active constituent, thymoquinone (TQ), have demonstrated antifungal activity against Candida species, supporting their investigation as natural product-based partners in synergistic antifungal combinations. Commercially prepared BSO and purified TQ were tested across a range of concentrations in a broth microdilution assay in combination with EB and novel organoselenium analogs, including Ebselen Oxide (EB-Ox) and N-octyl-1,2-benzisoselenazol-3(2H)-one (APM C6). Minimum inhibitory concentrations (MICs) for single agents and combinations were determined, and the resulting datasets were analyzed using the web-based Synergy Finder platform. EB, EB-Ox, and APM C6 showed consistent synergy with BSO and TQ against C. albicans (clinical isolate S1), as indicated by positive synergy scores relative to monotherapies.