Current Drug Targets - Volume 26, Issue 13, 2025

Poor solubility remains a significant obstacle in drug administration, adversely affecting the bioavailability and therapeutic efficacy of many drugs. It is also recognized as a primary factor contributing to issues with bioavailability, such as poor, inconsistent, limited, and highly variable bioavailability of marketed products. It is estimated that 40% of marketed drugs face bioavailability challenges primarily due to poor water solubility, and about 90% of pharmacological compounds exhibit poor water solubility in their early development stages. Addressing this issue is crucial for improving drug performance, efficacy, and patient outcomes. This review provides an overview of the challenges associated with poorly soluble drugs, including low bioavailability, limited dissolution rates, inconsistent absorption, decreased patient compliance, formulation difficulties, and associated costs and time constraints. Numerous strategies have been now investigated to tackle the issue of poor solubility. This review offers an updated overview of commonly used macro and nano drug delivery systems, including micelles, nanoemulsions, dendrimers, liposomes, lipid-based delivery systems, microemulsions, cosolvents, polymeric micelle preparation, drug nanocrystals, solid dispersion methods, crystal engineering techniques, and microneedle-based systems. Additionally, the review examines advanced techniques like cyclodextrin-based delivery systems, co-solvency and co-crystallization approaches, polymeric micelles, spray drying, co-precipitation, and amorphous solid dispersion. The role of computational modeling and formulation prediction is also addressed. Recent advancements in protein-based approaches, 3D printing, mesoporous silica nanoparticles, supramolecular delivery systems, magnetic nanoparticles, nanostructured lipid carriers, and lipid-based nanoparticles are highlighted as novel solutions for enhancing the solubility of poorly soluble drugs. The review concludes with predictions for the future, emphasizing the potential for further innovation in drug delivery methods to overcome the challenges associated with poorly soluble drugs.

Numerous bladder-related diseases, including urinary blockages, interstitial cystitis, overactive bladder syndrome, cancer, and infections of the urinary tract, can affect bladder function. The human urinary bladder's distinct anatomy successfully prevents any hazardous material from entering circulation. The pathogenesis was assessed according to the extent of invasion in the bladder wall tissue obtained through Transurethral Resection of Bladder Tumor (TURBT) and classified as Muscle-Invasive and Non-Muscle Invasive Bladder Cancer (MBIC and NMIBC). Intravesical Drug Delivery (IDD) has recently gained attention for treating bladder disorders. IDD refers to the insertion of a drug directly into the bladder using a catheter. Intravesical administration of immunotherapy or chemotherapy has been demonstrated to reduce recurrence rates and inhibit disease progression. In addition, several other systems, including recombinant BCG, gene therapy, vectors, and Antibody-Drug Conjugates (ADCs), are now used. Moreover, the novel intravesical formulations of distinct chemotherapeutic agents, including gemcitabine, Doxorubicin (DOX), and Mitomycin C (MMC), are used in bladder-related problems. Novel intravesical drugs, polymeric hydrogels, dendrimers, hydrogels, mucoadhesives, nanocarriers, and intravesical devices have been discussed. Aside from chemotherapy and immunotherapy, devices such as GemRIS, device-assisted hyperthermic intravesical chemotherapy, and photodynamic therapy are utilized.