Karthik Mangu, Ruhan Gudeli, Md. Rizwanullah
Oral chemotherapy offers an attractive alternative to conventional intravenous administration by providing high patient compliance and improved treatment adherence. However, several challenges, like poor drug solubility, enzymatic degradation, and extensive first-pass metabolism, have significantly limited the oral bioavailability of chemotherapeutic agents. Recently, polymeric nanoparticles (PNPs) have become an alternative strategy to overcome these challenges and revolutionize the oral chemotherapeutic approach. PNPs offer unique advantages, including drug protection from harsh gastrointestinal conditions, controlled release profiles, and enhanced mucosal adhesion, which collectively improve drug absorption and therapeutic efficacy. Additionally, surface-modified PNPs can bypass efflux transporters such as P-glycoprotein and promote receptor-mediated endocytosis to achieve targeted delivery and minimize systemic toxicity. While these advancements highlight the transformative potential of PNPs in oral chemotherapy, potential clinical challenges such as scalability, reproducibility, and regulatory hurdles must be addressed to enable successful clinical translation. The present review comprehensively explores the role of PNPs in enhancing the oral delivery of cancer therapeutics, emphasizing strategies to improve drug stability, prolong gastrointestinal retention, and facilitate efficient cellular uptake. The advancements discussed herein underscore the transformative potential of PNPs as a pivotal approach for improving oral chemotherapy outcomes and expanding therapeutic possibilities in cancer management.