Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy

Author(s)

Eloy, Josimar O. ^{[1, 2]} ; Petrilli, Raquel ^{[1, 2]} ; Topan, Jose Fernando ^[1] ; Ribeiro Antonio, Heriton Marcelo ^[3] ; Abriata Barcellos, Juliana Palma ^[1] ; Chesca, Deise L. ^[3] ; Serafini, Luciano Neder ^[3] ; Tiezzi, Daniel G. ^[3] ; Lee, Robert J. ^[2] ; Marchetti, Juliana Maldonado ^[1]

Affiliation

^[1] Univ Sao Paulo, Coll Pharmaceut Sci Ribeirao Preto, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil

^[2] Ohio State Univ, Coll Pharm, 500 W 12Th Ave, Columbus, OH 43210 - USA

^[3] Univ Sao Paulo, Sch Med Ribeirao Preto, Ave Bandeirantes S-N, BR-14040040 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: COLLOIDS AND SURFACES B-BIOINTERFACES; v. 141, p. 74-82, MAY 1 2016.
• Web of Science Citations: 37

Abstract

Paclitaxel and rapamycin have been reported to act synergistically to treat breast cancer. Albeit paclitaxel is available for breast cancer treatment, the most commonly used formulation in the clinic presents side effects, limiting its use. Furthermore, both drugs present pharmacokinetics drawbacks limiting their in vivo efficacy and clinic combination. As an alternative, drug delivery systems, particularly liposomes, emerge as an option for drug combination, able to simultaneously deliver co-loaded drugs with improved therapeutic index. Therefore, the purpose of this study is to develop and characterize a co-loaded paclitaxel and rapamycin liposome and evaluate it for breast cancer efficacy both in vitro and in vivo. Results showed that a SPC/Chol/DSPE-PEG (2000) liposome was able to co-encapsulate paclitaxel and rapamycin with suitable encapsulation efficiency values, nanometric particle size, low polydispersity and neutral zeta potential. Taken together, FTIR and thermal analysis evidenced drug conversion to the more bioavailable molecular and amorphous forms, respectively, for paclitaxel and rapamycin. The pegylated liposome exhibited excellent colloidal stability and was able to retain drugs encapsulated, which were released in a slow and sustained fashion. Liposomes were more cytotoxic to 4T1 breast cancer cell line than the free drugs and drugs acted synergistically, particularly when co-loaded. Finally, in vivo therapeutic evaluation carried out in 4T1-tumor-bearing mice confirmed the in vitro results. The co-loaded paclitaxel/rapamycin pegylated liposome better controlled tumor growth compared to the solution. Therefore, we expect that the formulation developed herein might be a contribution for future studies focusing on the clinical combination of paclitaxel and rapamycin. (C) 2016 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 14/08462-6 - Development and characterization of nanoparticles with polycaprolactone containing paclitaxel targeted with bevacizumab for optimization of ovarian cancer therapy
• Grantee: Juliana Maldonado Marchetti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 13/05362-8 - Functionalization of liposomes containing metformin and paclitaxel with trastuzumab: development, characterization and evaluation of efficacy against breast cancer
• Grantee: Josimar de Oliveira Eloy
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• FAPESP's process: 12/21513-3 - Strategies for paclitaxel and metformin vehiculation to improve breast cancer therapy: liposomes and dendrimers
• Grantee: Juliana Maldonado Marchetti
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/10388-3 - Liposomes and immunoliposomes containing anticancer drugs: development, characterization and efficacy evaluation against breast cancer
• Grantee: Josimar de Oliveira Eloy
• Support Opportunities: Scholarships in Brazil - Doctorate