Optimized Polyethylene Glycolylated Polymer-Lipid Hybrid Nanoparticles as a Potential Breast Cancer Treatment.

Salam Massadeh,Khulud Alhelal,Fayez H Alanazi,Wejdan Almotairi,Fares Almutairi,Abdulaziz Almalik,Manal Alaamery,Aiman A Obaidat,Asmaa Alterawi,Rizwan Ali,Mustafa E Omer,Alaa Eldeen Yassin,Faris F Alobaidi,Mansour S Almutairi

doi:10.3390/pharmaceutics12070666

Abstract

Purpose: The aim of this work is to optimize a polyethylene glycolated (PEGylated) polymer–lipid hybrid nanoparticulate system for the delivery of anastrozole (ANS) to enhance its biopharmaceutical attributes and overall efficacy. Methods: ANS loaded PEGylated polymer–lipid hybrid nanoparticles (PLNPs) were prepared by a direct emulsification solvent evaporation method. The physical incorporation of PEG was optimized using variable ratios. The produced particles were evaluated to discern their particle size and shape, zeta-potential, entrapment efficiency, and physical stability. The drug-release profiles were studied, and the kinetic model was analyzed. The anticancer activity of the ANS PLNPs on estrogen-positive breast cancer cell lines was determined using flow cytometry. Results: The prepared ANS-PLNPs showed particle sizes in the range of 193.6 ± 2.9 to 218.2 ± 1.9 nm, with good particle size uniformity (i.e., poly-dispersity index of around 0.1). Furthermore, they exhibited relatively low zeta-potential values ranging from −0.50 ± 0.52 to 6.01 ± 4.74. The transmission electron microscopy images showed spherical shape of ANS-PLNPs and the compliance with the sizes were revealed by light scattering. The differential scanning calorimetry DSC patterns of the ANS PLNPs revealed a disappearance of the characteristic sharp melting peak of pure ANS, supporting the incorporation of the drug into the polymeric matrices of the nanoparticles. Flow cytometry showed the apoptosis of MCF-7 cell lines in the presence of ANS-PLNPs. Conclusion: PEGylated polymeric nanoparticles presented a stable encapsulated system with which to incorporate an anticancer drug (ANS) with a high percentage of entrapment efficiency (around 80%), good size uniformity, and induction of apoptosis in MCF-7 cells.

Highlights

Breast cancer is considered to be the second leading cause of cancer-related death both worldwide and in Saudi Arabia [1]
We evaluated the apoptotic response of the ANS-polymer–lipid hybrid nanoparticles (PLNPs) in breast cancer cell lines
Using the particle size analyzer (ZetaPALS; Brookhaven Instruments, Holtsville, NY, USA), the zeta-potential was measured for all formulations (T1, P1, P2, and P3) by applying the laser Doppler velocimetry (LDV) mode

Summary

Introduction

Breast cancer is considered to be the second leading cause of cancer-related death both worldwide and in Saudi Arabia [1]. Anastrazole (ANS), a third-generation aromatase inhibitor, has been proven to be superior to tamoxifen for reducing the recurrence of invasive breast cancer in postmenopausal women who are hormone-receptor positive [7]. Anastrazole was recommended as a rational treatment option for hormone-receptor positive postmenopausal women with ductal carcinoma in situ [8]. It demonstrated significant reduction in the most serious adverse effects of tamoxifen, i.e., ischaemic cerebrovascular disorders and development of endometrial cancer [9]. The poor aqueous solubility of ANS results in variation of intestinal absorption and highly variable blood levels leading to undesirable side effect including thrombocytosis, osteoporosis, and vaginal bleeding [11]

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