Preparation and characterization of letrozole-loaded poly(d,l-lactide) nanoparticles for drug delivery in breast cancer therapy

Abstract

Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations. Loaded drug and drug-polymer interactions were studied using X-ray diffraction and NPs morphology was evaluated using scanning electron microscopy (SEM). Particle size distribution (PSD) and zeta potential of the NPs were analyzed using dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), respectively. Drug content and release profile studies were carried out and determined using ultra performance liquid chromatography (UPLC). The yield of LTZ-PDLLA NPs reached as high as 85%. The NPs were spherical and smooth, regardless of LTZ concentration in the formulation. However, particle size increased from 241.6 ± 1.2 to 348.7 ± 6.1 nm upon increasing LTZ concentration from 0 to 30% w/w, with entrapment efficiencies reaching up to 96.8%. Drug release from the polymeric matrix was best described by Higuchi model with a predominant diffusion-based mechanism. More than 15, 46, and 86% of LTZ was released in a controlled fashion over 30 d from the 10, 20, and 30% LTZ-PDLLA NPs, respectively. Overall, LTZ-PDLLA NPs were designed with appropriate size and surface charge, high drug loading, superior entrapment efficiency, and prolonged release profile.

Keywords:

• Breast cancer
• letrozole
• poly(d,l-lactide)
• nanoparticles
• sustained drug release

Acknowledgments

The authors would like to thank Dr. Saeed Al-Meer, Dr. Mohamed Yousef, and Mr. Essam Mohamed at the Central Lab Unit of Qatar University for their assistance with the SEM studies.

Bayan Alemrayat is the graduate student who carried out the experiments. Abdelbary Elhissi helped in supervising Bayan and commented on the manuscript. Husam Younes designed the research question, designed performed experiments, analysed data, supervised the progress of the project and wrote the final manuscript.

Disclosure statement

The authors declare that they do not have any conflict of interest.

Additional information

Funding

This work was supported by a research grant from Qatar University (Grant number: QUST-CPH-SPR-14/15–5) granted to Dr. Husam Younes.