Details

Autor(en) / Beteiligte

• Yang, Shili
• Lin, Hai-Shu
• Zhang, Li
• Chi-Lui Ho, Paul

Titel

Formulating 10-hydroxycamptothecin into nanoemulsion with functional excipient tributyrin: An innovative strategy for targeted hepatic cancer chemotherapy

Ist Teil von

• International journal of pharmaceutics, 2024-04, Vol.654, p.123945-123945, Article 123945

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2024

Quelle

ScienceDirect

Beschreibungen/Notizen

• Formulating 10-hydroxycamptothecin into nanoemulsion (Tri-HCPT-E) with functional excipient tributyrin not only promoted its stability but also enhanced its hepatic targeting, resulting in a superior in vivo anti-cancer efficacy. [Display omitted] •10-hydroxycamptothecin was formulated into nanoemulsion using tributyrin.•The solubility and stability of 10-hydroxycamptothecin were substantially enhanced.•The nanoemulsion exhibited superior hepatic targeting and anti-cancer efficacy. This study aimed to develop an innovative dosage form for 10-hydroxycamptothecin (HCPT), a chemotherapeutic agent with limited aqueous solubility and stability, to enhance its parenteral delivery and targeting to hepatic cancer. We formulated HCPT into a nanoemulsion using tributyrin, a dietary component with histone deacetylase inhibitor activity. The resulting HCPT-loaded tributyrin nanoemulsion (Tri-HCPT-E) underwent extensive evaluations. Tri-HCPT-E significantly improved the aqueous solubility, stability, and anti-cancer activities in HepG2 cells. Pharmacokinetic studies confirmed the increased stability and hepatic targeting, with Tri-HCPT-E leading to a 120-fold increase in plasma exposure of intact HCPT and a 10-fold increase in hepatic exposure compared to the commercial free solution. Co-administration of 17α-ethynylestradiol, an up-regulator of low-density lipoprotein (LDL) receptor, further enhanced the distribution and metabolism of HCPT, demonstrating an association between the LDL receptor pathway and hepatic targeting. Most importantly, Tri-HCPT-E exhibited superior in vivo anti-cancer efficacy in a mouse xenograft model compared to the commercial formulation, without causing escalated hepatic or renal toxicity. In conclusion, formulating HCPT into a nanoemulsion with tributyrin has proven to be an innovative and effective strategy for targeted hepatic cancer chemotherapy while tributyrin, a pharmacologically active dietary component, has emerged as a promising functional excipient for drug delivery.