Polymeric Therapeutic Nanosystems Containing Paclitaxel: Novel Strategies, Therapeutic Potential, Challenges, and...

Cancers still remain one of the most significant challenges in medicine or pharmacy, accounting for nearly 10 million deaths annually and imposing a substantial socioeconomic burden worldwide. Although chemotherapy continues to play a central role in the treatment of many tumors, conventional anticancer therapies are frequently associated with poor selectivity, systemic toxicity, multidrug resistance, and unfavorable pharmacokinetic profiles. Paclitaxel (PTX), one of the most widely used antineoplastic agents, demonstrates remarkable clinical efficacy against breast, ovarian, lung, pancreatic, and several other malignancies. Nevertheless, its clinical application remains limited by poor aqueous solubility, non-specific biodistribution, dose-limiting toxicities, and the development of resistance mechanisms. Nanotechnology-based anticancer drug delivery systems have emerged as a promising strategy to address these limitations. Among them, polymeric nanosystems have attracted particular attention owing to their physicochemical properties, biocompatibility, controlled drug-release capabilities, and potential for tumor-targeted delivery. Natural, semi-synthetic, and synthetic polymers are extensively investigated as carriers for PTX, leading to the development of nanoparticles, micelles, nanogels, nanofibers, dendritic systems, and hybrid nanoplatforms. Nanosystems demonstrate enhanced therapeutic efficacy, reduced systemic toxicity, prolonged circulation times, and improved tumor accumulation in preclinical models. Despite encouraging laboratory results, the clinical translation of polymeric PTX nanocarriers (NCs) remains limited. Numerous barriers, including tumor heterogeneity, variability of the enhanced permeability and retention (EPR) effect, manufacturing complexity, regulatory challenges, scale-up difficulties, and discrepancies between animal models and human cancers, continue to hinder successful commercialization and widespread clinical adoption. This review critically discusses the current state of polymeric drug delivery systems (DDSs) that contain PTX, as well as the advantages and limitations of synthetic, natural, and semi-synthetic polymers used in DDS technologies. Furthermore, translational challenges and future perspectives of PTX-based DDSs were analyzed.