Preparation and optimization of monodisperse polymeric microparticles using modified vibrating orifice aerosol generator for controlled delivery of letrozole in breast cancer therapy

Abstract

Letrozole (LTZ) is effective for the treatment of hormone-receptor-positive breast cancer in postmenopausal women. In this work, and for the first time, using vibrating orifice aerosol generator (VOAG) technology, monodisperse poly-ε-caprolactone (PCL), and poly (D, L-Lactide) (PDLLA) LTZ-loaded microparticles were prepared and found to elicit selective high cytotoxicity against cancerous breast cells with no apparent toxicity on healthy cells in vitro. Plackett-Burman experimental design was utilized to identify the most significant factors affecting particle size distribution to optimize the prepared particles. The generated microparticles were characterized in terms of microscopic morphology, size, zeta potential, drug entrapment efficiency, and release profile over one-month period. Long-term cytotoxicity of the microparticles was also investigated using MCF-7 human breast cancer cell lines in comparison with primary mammary epithelial cells (MEC). The prepared polymeric particles were monodispersed, spherical, and apparently smooth, regardless of the polymer used or the loaded LTZ concentration. Particle size varied from 15.6 to 91.6 µm and from 22.7 to 99.6 µm with size distribution (expressed as span values) ranging from 0.22 to 1.24 and from 0.29 to 1.48 for PCL and PDLLA based microparticles, respectively. Upon optimizing the manufacture parameters, span was reduced to 0.162-0.195. Drug entrapment reached as high as 96.8%, and drug release from PDLLA and PCL followed a biphasic zero-order release using 5 or 30% w/w drug loading in the formulations. Long-term in vitro cytotoxicity studies indicated that microparticles formulations significantly inhibited the growth of MCF-7 cell line over a prolonged period of time but did not have toxic effects on the normal breast epithelial cells.

A review of FDA approved drugs and their formulations for the treatment of breast cancer

“…The size of formulation at least doubles the AUC, suggesting that the dose might be halved, thereby reducing side effects associated with this otherwise important drug. Recently, an Iron-Doped Fullerene Cage of Thiotepa has been prepared by Xuan Young to modify drug delivery (Alemrayat et al, 2018;Pandey et al, 2020). C3 N nanotubes (Ge et al, 2012;Torabifard and Fattahi, 2012;Fox et al, 2021).…”

“…It has poor water solubility, rapid metabolism, and a range of side effects. Polymer-based nanoparticles (FDA, 2012a;Alemrayat et al, 2018;Caulfield et al, 2019;Leo et al, 2020), Lipid nanocomplex (Bhatnagar, 2007;Azandaryani et al, 2019;Yassemi et al, 2020), solid lipid nanoparticles (Khan et al, 2022), Pegylated nanoparticles (Kelly and Buzdar, 2010), are few of the novel formulations explored to overcome the limitations and side effects associated with Letrozole.s.…”

Microsponge as an Emerging Technique in Novel Drug Delivery System

“…Lastly, through filtration, washing, centrifuging and by drying, solidified micro particles were obtained. 36…”

Monodisperse Fluorescent Polystyrene Microspheres for Staphylococcus aureus Aerosol Simulation

“…Both methods can generate monodisperse particles and both offer flexibility in the size of the emulsions generated. In addition, monodisperse poly-ε-caprolactone was prepared by Alemrayat et al using vibrating orifice aerosol generator technology for the first time in 2018 [29]. Electrohydrodynamic atomization, a subfield of fluid mechanics, is also used in the preparation of monodisperse microspheres.…”