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Co-loaded paclitaxel/rapamycin liposomes: Development, characterization and in vitro and in vivo evaluation for breast cancer therapy
- Source :
- Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual), Universidade de São Paulo (USP), instacron:USP
- Publication Year :
- 2016
- Publisher :
- Elsevier BV, 2016.
-
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.
- Subjects :
- Drug
Paclitaxel
Cell Survival
media_common.quotation_subject
Biological Availability
02 engineering and technology
Pharmacology
Article
Polyethylene Glycols
Mice
03 medical and health sciences
chemistry.chemical_compound
Drug Delivery Systems
0302 clinical medicine
Colloid and Surface Chemistry
Therapeutic index
Breast cancer
Microscopy, Electron, Transmission
Pharmacokinetics
In vivo
Cell Line, Tumor
Antineoplastic Combined Chemotherapy Protocols
Spectroscopy, Fourier Transform Infrared
medicine
Animals
Physical and Theoretical Chemistry
media_common
Sirolimus
Mice, Inbred BALB C
Liposome
ANTINEOPLÁSICOS
Chemistry
Phosphatidylethanolamines
Mammary Neoplasms, Experimental
Surfaces and Interfaces
General Medicine
021001 nanoscience & nanotechnology
medicine.disease
Survival Analysis
Treatment Outcome
030220 oncology & carcinogenesis
Liposomes
Drug delivery
Female
0210 nano-technology
Biotechnology
Subjects
Details
- ISSN :
- 09277765
- Volume :
- 141
- Database :
- OpenAIRE
- Journal :
- Colloids and Surfaces B: Biointerfaces
- Accession number :
- edsair.doi.dedup.....e365d5be81d6620d3a42207ac185478e
- Full Text :
- https://doi.org/10.1016/j.colsurfb.2016.01.032