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

Co-encapsulation of paclitaxel and C6 ceramide in tributyrin-containing nanocarriers improve co-localization in the skin and potentiate cytotoxic effects in 2D and 3D models

Full text
Author(s):
Carvalho, Vanessa F. M. [1] ; Migotto, Amanda [1] ; Giacone, Daniela V. [1] ; de Lemos, Debora P. [1] ; Zanoni, Thalita B. [2] ; Maria-Engler, Silvya S. [2] ; Costa-Lotufo, Leticia V. [1] ; Lopes, Luciana B. [1]
Total Authors: 8
Affiliation:
[1] Univ Sao Paulo, Inst Biomed Sci, Sao Paulo - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: European Journal of Pharmaceutical Sciences; v. 109, p. 131-143, NOV 15 2017.
Web of Science Citations: 9
Abstract

Considering that tumor development is generally multifactorial, therapy with a combination of agents capable of potentiating cytotoxic effects is promising. In this study, we co-encapsulated C6 ceramide (0.35%) and paclitaxel (0.50%) in micro and nanoemulsions containing tributyrin (a butyric acid pro-drug included for potentiation of cytotoxicity), and compared their ability to co-localize the drugs in viable skin layers. The nanoemulsion delivered 2- and 2.4-fold more paclitaxel into viable skin layers of porcine skin in vitro at 4 and 8 h post-application than the microemulsion, and 1.9-fold more C6 ceramide at 8 h. The drugs were co-localized mainly in the epidermis, suggesting the nanoemulsion ability for a targeted delivery. Based on this result, the nanoemulsion was selected for evaluation of the nanocarrier-mediated cytotoxicity against cells in culture (2D model) and histological changes in a 3D melanoma model. Encapsulation of the drugs individually decreased the concentration necessary to reduce melanoma cells viability to 50% (EC50) by approximately 4- (paclitaxel) and 13-fold (ceramide), demonstrating an improved nanoemulsion-mediated drug delivery. Co-encapsulation of paclitaxel and ceramide further decreased EC50 by 2.5-4.5-fold, and calculation of the combination index indicated a synergistic effect. Nanoemulsion topical administration on 3D bioengineered melanoma models for 48 h promoted marked epidermis destruction, with only few cells remaining in this layer. This result demonstrates the efficacy of the nanoemulsion, but also suggests non-selective cytotoxic effects, which highlights the importance of localizing the drugs within cutaneous layers where the lesions develop to avoid adverse effects. (AU)

FAPESP's process: 14/24400-0 - In vitro models for pre clinical studies of melanoma Chemoresistant
Grantee:Silvya Stuchi Maria-Engler
Support type: Regular Research Grants
FAPESP's process: 15/23976-9 - Development, characterization and evaluation of microemulsions for paclitaxel and ceramide C6 topical delivery
Grantee:Amanda Migotto
Support type: Scholarships in Brazil - Scientific Initiation
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 type: Research Grants - Young Investigators Grants
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 type: Scholarships in Brazil - Scientific Initiation