Permeability evaluation of gemcitabine-CPP6 conjugates in Caco-2 cells

• Type: Article in International Scientific Journal
• Date: 2021

Authors

Ferreira, A (Author) Other; Moreira, Sara (Author) Other; Lapa, R (Author) Other; Nuno Vale (Author) FMUP

Journal

The Journal is awaiting validation by the Administrative Services.

Title: ADMET AND DMPK

Vol. 9

Pages: 41-48

ISSN: 1848-7718

Indexing

ISI Web of Knowledge - 1 Citation

Scopus - 0 Citations

Other information

Authenticus ID: P-00T-705

DOI: 10.5599/admet.882

Abstract (EN): Cancer is one of the most alarming diseases due to its high mortality and still increasing incidence rate. Currently available treatments for this condition present several shortcomings and new options are continuously being developed and evaluated, aiming at increasing the overall treatment efficiency and reducing associated adverse side effects. Gemcitabine has proven activity and is used in chemotherapy. However, its therapeutic efficiency is limited by its low bioavailability as a result of rapid enzymatic inactivation. Additionally, tumor cells often develop drug resistance after initial tumor regression related to transporter deficiency. We have previously developed three gemcitabine conjugates with cell-penetrating hexapeptides (CPP6) to facilitate intracellular delivery of this drug while also preventing enzymatic deamination. The bioactivity of these new prodrugs was evaluated in different cell lines and showed promising results. Here, we assessed the absorption and permeability across Caco-2 monolayers of these conjugates in comparison with gemcitabine and the respective isolated cell-penetrating peptides (CPPs). CPP6-2 (KLPVMW) and respective Gem-CPP6-2 conjugate showed the highest permeability in Caco-2 cells. (c) 2021 by the authors. This article is an open-access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8