Abstract

TOFACITINIB NANOCRYSTALS STABILIZED WITH PLURONIC F127 AND FUNCTIONALIZED WITH FOLIC ACID: A REVIEW OF DRUG REPURPOSING, TARGETED DELIVERY, AND POTENTIAL ANTICANCER APPLICATIONS

Swapna Paul*, Dr. Vivek Chauhan1

ABSTRACT

Cancer therapy continues to face challenges associated with inadequate drug delivery, limited tumor selectivity, drug resistance, and treatment-related toxicity. Drug repurposing and nanotechnology offer potential approaches to address these limitations. This review explores the rationale for investigating tofacitinib, a Janus kinase (JAK) inhibitor, as a potential anticancer candidate and discusses the proposed development of Pluronic F127-stabilized, folic acid-functionalized tofacitinib nanocrystals. The review examines the role of JAK/STAT signaling in tumor-associated processes, the pharmaceutical advantages of drug nanocrystals, the stabilizing properties of Pluronic F127, and the potential of folic acid to promote receptor-mediated cellular uptake in folate receptor-expressing cancer cells. Published preclinical evidence suggests that tofacitinib can modulate JAK/STAT signaling in selected cancer models, while studies in experimental inflammatory models indicate potential effects on angiogenesis-related pathways. Nanocrystal formulation may improve dissolution behavior by increasing the surface area available for dissolution, whereas Pluronic F127 may help maintain dispersion stability. Folic acid functionalization may facilitate cellular interaction and uptake in receptor-expressing cells. However, these benefits remain hypotheses for the proposed formulation and require experimental validation. Further studies should evaluate particle size, polydispersity, crystallinity, dissolution, stability, receptor-mediated cellular uptake, cytotoxicity, JAK/STAT pathway modulation, and angiogenesis-related markers. In vivo investigations are also necessary to establish biodistribution, safety, and therapeutic potential. In conclusion, folic acid-functionalized, Pluronic F127-stabilized tofacitinib nanocrystals represent a promising research strategy for exploring drug repurposing in cancer therapy. Nevertheless, their targeting efficiency, biological activity, and potential anticancer efficacy remain to be established through systematic preclinical and clinical investigations.

Keywords: Tofacitinib; Nanocrystals; Pluronic F127; Folic acid; Drug repurposing; Targeted drug delivery; JAK/STAT signaling; Anticancer drug delivery.