Role of Nanoformulations in Enhancing Curcumin Bioavailability: Innovations in Targeted and Sustained Cancer Therapy

Abstract

Curcumin, a natural diphenolic compound isolated from Curcuma longa, possesses significant anticancer activity through modulation of signaling pathways involved in proliferation, inflammation, invasion, angiogenesis, and apoptosis. However, its clinical application is restricted by poor aqueous solubility, rapid metabolism, chemical instability, and low systemic bioavailability. This review summarizes recent advancements in curcumin delivery strategies, focusing on nano-engineered systems designed to enhance bioavailability, stability, and targeted anticancer efficacy. Recent studies on curcumin nanoformulations, including liposomes, polymeric nanoparticles, nanogels, micelles, self-assembled systems, and multifunctional nanocomposites, were critically analyzed. Key aspects evaluated included encapsulation efficiency, pharmacokinetic enhancement, controlled release, targeted delivery, and potential for combination therapy. Nanoformulations significantly enhance curcumin solubility, metabolic stability, systemic absorption, and tumor accumulation. These systems facilitate controlled drug release, receptor-mediated uptake, and multifunctional applications such as imaging-guided and combinational therapy. Preclinical studies demonstrated enhanced anticancer activity, apoptosis induction, tumor growth inhibition, and reduced systemic toxicity compared with free curcumin. Nano-curcumin systems also modulate major cancer-associated signaling pathways, including PI3K/AKT, MAPK, NF-κB, STAT3, and Wnt/β-catenin. Although substantial progress has been achieved, several challenges continue to hinder the clinical translation of curcumin nanoformulations, including long-term stability, large-scale manufacturing, reproducibility, targeted delivery efficiency, pharmacokinetic variability, regulatory approval, and limited clinical validation. Nano-engineered curcumin formulations represent promising strategies to overcome pharmacokinetic limitations and improve anticancer efficacy, supporting future clinical applications in cancer therapy.