International Journal of Nanomedicine (Dec 2017)
Preparation of anastrozole loaded PEG-PLA nanoparticles: evaluation of apoptotic response of breast cancer cell lines
Abstract
Yusra A Alyafee,1,2 Manal Alaamery,1 Shahad Bawazeer,1 Mansour S Almutairi,1 Badr Alghamdi,1 Nawaf Alomran,1 Atia Sheereen,1 Maha Daghestani,2 Salam Massadeh1,3 1Developmental Medicine Department, King Abdullah International Medical Research Center, King Saud Bin Abdulaziz University for Health Sciences, King AbdulAziz Medical City, Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia; 2Department of Zoology/College of Science/King Saud University (KSU), Riyadh, Kingdom of Saudi Arabia; 3College of Pharmacy, King Saud bin Abdulaziz University for Health Sciences, King Abdullah International Medical Research Center, King Abdulaziz Medical City, Ministry of National Guard, Health Affairs, Riyadh, Kingdom of Saudi Arabia Purpose: Anastrozole (ANS) is an aromatase inhibitor that is widely used as a treatment for breast cancer in postmenopausal women. Despite the wide use of ANS, it is associated with serious side effects due to uncontrolled delivery. In addition, ANS exhibits low solubility and short plasma half-life. Nanotechnology-based drug delivery has the potential to enhance the efficacy of drugs and overcome undesirable side effects. In this study, we aimed to prepare novel ANS-loaded PLA-PEG-PLA nanoparticles (ANS-NPs) and to compare the apoptotic response of MCF-7 cell line to both ANS and ANS-loaded NPs.Method: ANS-NPs were synthesized using double emulsion method and characterized using different methods. The apoptotic response was evaluated by assessing cell viability, morphology, and studying changes in the expression of MAPK3, MCL1, and c-MYC apoptotic genes in MCF-7 cell lines.Results: ANS was successfully encapsulated within PLA-PEG-PLA, forming monodisperse therapeutic NPs with an encapsulation efficiency of 67%, particle size of 186±27.13, and a polydispersity index of 0.26±0.11 with a sustained release profile extended over 144 hours. In addition, results for cell viability and for gene expression represent a similar apoptotic response between the free ANS and ANS-NPs.Conclusion: The synthesized ANS-NPs showed a similar therapeutic effect as the free ANS, which provides a rationale to pursue pre-clinical evaluation of ANS-NPs on animal models. Keywords: anastrozole, PLA-PEG-PLA, anti-apoptosis, gene expression, therapeutic nanoparticles
