Advanced search
Start date
Betweenand
Related content
(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Evidence That P-glycoprotein Inhibitor (Elacridar)-Loaded Nanocarriers Improve Epidermal Targeting of an Anticancer Drug via Absorptive Cutaneous Transporters Inhibition

Full text
Author(s):
Giacone, Daniela V. [1] ; Carvalho, Vanessa F. M. [1] ; Costa, Soraia K. P. [1] ; Lopes, Luciana B. [1]
Total Authors: 4
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
Total Affiliations: 1
Document type: Journal article
Source: Journal of Pharmaceutical Sciences; v. 107, n. 2, p. 698-705, FEB 2018.
Web of Science Citations: 3
Abstract

Because P-glycoprotein (P-gp) plays an absorptive role in the skin, its pharmacological inhibition represents a strategy to promote cutaneous localization of anticancer agents that serve as its substrates, improving local efficacy while reducing systemic exposure. Here, we evaluated the ability of a nanoemulsion (NE) coencapsulating a P-gp inhibitor (elacridar) with the antitumor drug paclitaxel to promote epidermal targeting. Loaded NE displayed a nanometric size (45.2 +/- 4.0 nm) and negative zeta potential (-4.2 +/- 0.8 mV). Elacridar improved NE ability to inhibit verapamil-induced ATPase activity of P-gp; unloaded NE-inhibited P-gp when used at a concentration of 1500 mM, while elacridar encapsulation decreased this concentration by 3-fold (p < 0.05). Elacridar-loaded NE reduced paclitaxel penetration into the dermis of freshly excised mice skin and its percutaneous permeation by 1.5-and 1.7-fold (p < 0.05), respectively at 6 h, whereas larger drug amounts (1.4-fold, p < 0.05) were obtained in viable epidermis. Assessment of cutaneous distribution of a fluorescent paclitaxel derivative confirmed the smaller delivery into the dermis at elacridar presence. In conclusion, we have provided novel evidence that NE containing elacridar exhibited a clear potential for P-gp inhibition and enabled epidermal targeting of paclitaxel, which in turn, can potentially reduce adverse effects associated with systemic exposure to anticancer therapy. (c) 2018 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved. (AU)

FAPESP's process: 16/04913-9 - Evaluation of cationic microemulsions as systems capable of increasing cutaneous retention and cytotoxicity of drugs
Grantee:Daniela Veronesi Giacone
Support Opportunities: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 14/50928-2 - INCT 2014: Pharmaceutical Nanotechnology: a transdisciplinary approach
Grantee:Maria Vitória Lopes Badra Bentley
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/16617-7 - Nanostructured systems for topical delivery and co-localization of chemopreventive and chemoterapeutic agents in the skin and breast tissue
Grantee:Luciana Biagini Lopes
Support Opportunities: Research Grants - Young Investigators Grants
FAPESP's process: 16/06146-5 - Bioavailability of Hydrogen Sulfide in a topical nanoformulation in experimental psoriasis
Grantee:Soraia Katia Pereira Costa
Support Opportunities: Regular Research Grants
FAPESP's process: 13/04151-3 - Pharmacological evaluation of sulfide hydrogen donors (rapid and slow release) in pruritus and related inflammation in mice skin
Grantee:Soraia Katia Pereira Costa
Support Opportunities: Regular Research Grants