Pyridoclax-loaded nanoemulsion for enhanced anticancer effect on ovarian cancer.
Cytotoxic activity
Nanoemulsions
Nanomedicine
Ovarian cancer
Pharmacokinetics
Journal
International journal of pharmaceutics
ISSN: 1873-3476
Titre abrégé: Int J Pharm
Pays: Netherlands
ID NLM: 7804127
Informations de publication
Date de publication:
25 Sep 2020
25 Sep 2020
Historique:
received:
02
12
2019
revised:
26
06
2020
accepted:
13
07
2020
pubmed:
28
7
2020
medline:
22
6
2021
entrez:
27
7
2020
Statut:
ppublish
Résumé
Pyridoclax is an original lead, recently identified as very promising in treatment of chemoresistant ovarian cancers. To correct the unfavorable intrinsic physico-chemical properties of this BCS II drug, a formulation strategy was implied in the drug discovery step. Pyridoclax-loaded nanoemulsions (NEs) were developed to permit its preclinical evaluation. The resulting nanoemulsions displayed a mean size of about 100 nm and a high encapsulation efficiency (>95%) at a drug loading of 2 wt%, enabling a 1,000-fold increase of the Pyridoclax apparent solubility. NEs have enabled a sustained release of the drug as assayed by a dialysis bag method. In addition, anti-tumor effects of the Pyridoclax-loaded nanoemulsions (PNEs) showed a 2.5-fold higher activity on chemoresistant ovarian cancer cells than free Pyridoclax. This effect was confirmed by a drastic increase of caspase 3/7 activation from 10 µM PNEs, as newly objectified by real time apoptose imaging. The Pyridoclax bioavailability was kept unchanged after encapsulation in nanoemulsions as determined in a mice model after oral administration. Thus, NEs should permit valuable Pyridoclax oral administration, and valorization of this promising anticancer drug by maintaining its original anticancer activity, and by reducing the Pyridoclax therapeutic concentration.
Sections du résumé
BACKGROUND
BACKGROUND
Pyridoclax is an original lead, recently identified as very promising in treatment of chemoresistant ovarian cancers. To correct the unfavorable intrinsic physico-chemical properties of this BCS II drug, a formulation strategy was implied in the drug discovery step. Pyridoclax-loaded nanoemulsions (NEs) were developed to permit its preclinical evaluation.
RESULTS
RESULTS
The resulting nanoemulsions displayed a mean size of about 100 nm and a high encapsulation efficiency (>95%) at a drug loading of 2 wt%, enabling a 1,000-fold increase of the Pyridoclax apparent solubility. NEs have enabled a sustained release of the drug as assayed by a dialysis bag method. In addition, anti-tumor effects of the Pyridoclax-loaded nanoemulsions (PNEs) showed a 2.5-fold higher activity on chemoresistant ovarian cancer cells than free Pyridoclax. This effect was confirmed by a drastic increase of caspase 3/7 activation from 10 µM PNEs, as newly objectified by real time apoptose imaging. The Pyridoclax bioavailability was kept unchanged after encapsulation in nanoemulsions as determined in a mice model after oral administration.
CONCLUSION
CONCLUSIONS
Thus, NEs should permit valuable Pyridoclax oral administration, and valorization of this promising anticancer drug by maintaining its original anticancer activity, and by reducing the Pyridoclax therapeutic concentration.
Identifiants
pubmed: 32712252
pii: S0378-5173(20)30639-6
doi: 10.1016/j.ijpharm.2020.119655
pii:
doi:
Substances chimiques
Emulsions
0
Pyridines
0
pyridoclax
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
119655Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.