Curcumin and its analogues in mucopenetrative nano-formulations for cancer therapy: current evidence, challenges, and...

Cancer remains a leading cause of mortality worldwide, whilst conventional therapy is constrained by severe side effects and drug resistance. Curcumin, derived from turmeric demonstrates anticancer, antioxidant, anti-inflammatory, and antitumor effects. However, translation into clinical use is hindered by low solubility/bioavailability and rapid degradation. These constraints have been addressed somewhat via advanced drug delivery technology, including nano-formulation or by chemical modification. Nano-formulations also permit targeted delivery of curcumin, as necessary in chronic therapy, where minimization of side effects is the prime focus. However, delivery to target tissue does not necessarily correlate with improved cellular uptake because physiological barriers that must be traversed before deployment into cells. In this regard, mucoadhesive nano-delivery may be indispensable in improving drug retention on mucosal surfaces. Crucially, mucopenetration of nano-formulations ensure effective transfer into cells, and improved bioavailability of the payload. In composing this review, relevant literature identified in major databases, including PubMed, ScienceDirect and Scopus, on curcumin, mucopenetration, nanocarriers, and cancer was sought. Studies were selected based relevance to formulation methods and biological evaluation. Data suggests a limited exploration of mucopenetrative nano-formulations of curcumin for improving cellular uptake. This review emphasizes the importance of imparting such functionality on nano-particulate delivery systems as an opportunity for enhanced therapeutics, using curcumin as a case study. We highlight the mechanisms of cellular uptake, efficacy, advantages that contribute to realizing the full clinical significance of curcumin in cancer treatment. Although preliminary findings are promising, direct evidence supporting curcumin-specific mucopenetrative nano-formulations in clinically relevant cancer models remains very limited.