Revitalizing Itraconazole: Unleashing its Anticancer Potential through Oral Nanosystems for Liver Targeting and Biodistribution Profiling in an Animal Model using Radiolabeling Technique

Hepatic cancer presents a global health challenge requiring innovative therapeutic approaches. In this study, we explore the need for novel drug delivery systems in hepatocellular carcinoma (HCC) treatment, focusing on targeted itraconazole delivery via bilosomes. Itraconazole, an antifungal with promising anticancer activity, necessitates systems enhancing efficacy and selectivity. In this study itraconazole-loaded bilosomes were optimized as a targeted drug delivery system. Entrapment efficiency, particle size, polydispersity index, and zeta potential were measured. By employing statistical analysis and numerical optimization, the optimized itraconazole-loaded bilosomes formulation (OIB) was identified. OIB was evaluated through in-vitro drug release kinetics, and morphological examination. OIB's targeting capability was investigated through radiolabeling biodistribution technique, and its anticancer activity is examined against HCC using the HepG cell line. OIB showed an entrapment efficiency of 77.5 % ± 0.1, a particle size of 366.2 nm ± 6.6, acceptable PDI, and a zeta potential of 57.3 mV ± 0.9. The optimized formulation exhibited sustained release with 61.9 % ± 0.9 % itraconazole released after 24 h, following the Higuchi diffusion model. Morphological examination revealed spherical morphology. Biodistribution studies using radiolabeled itraconazole confirmed targeted accumulation in hepatic cells, highlighting OIB's potential as a selective therapeutic agent. OIB demonstrated potent anticancer activity against HCC in the HepG cell line, validating its efficacy as a targeted treatment. Itraconazole-loaded bilosomes offer hope in combating hepatocellular carcinoma. Besides, 131 I-itraconazole loaded bilosomes can combine the radiotherapeutic effect of 131 I with the hopeful anticancer effect of itraconazole. This study supports bilosomes as a promising strategy against this deadly disease. • Itraconazole is a broad-spectrum FDA-approved triazole antifungal drug with reported anticancer activity. • Optimized Itraconazole bilosomes demonstrated a high EE, a suitable PS, and an excellent ZP. • Radiolabeling and biodistribution studies confirmed the accumulation of optimized Itraconazole bilosomes in hepatic cells. • Optimized Itraconazole bilosomes showed 53-fold enhancement in the potency of Itraconazole in HepG2 cell line.