Formulating 10-hydroxycamptothecin into nanoemulsion with functional excipient tributyrin: An innovative strategy for targeted hepatic cancer chemotherapy.
Int J Pharm
; 654: 123945, 2024 Apr 10.
Article
em En
| MEDLINE
| ID: mdl-38403088
ABSTRACT
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.
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Texto completo:
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Triglicerídeos
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Camptotecina
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Neoplasias Hepáticas
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Antineoplásicos Fitogênicos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article