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.

Nanoparticles/nanoplatform to carry and deliver the drug molecules to the target site

“…Obtained particles were spherical in shape with a size of 350 nm. High entrapment efficiency was obtained (96%) and the release profile was significantly improved [23].…”

Development and Characterization of Soy Lecithin Liposome as Potential Drug Carrier Systems for Codelivery of Letrozole and Paclitaxel

“…By successfully preventing aromatase which produces oestrogen, LET slows down the growth of hormone-responsive breast tumours in vivo. However, research has shown that LET has some negative effects on patients, including diarrhoea, constipation, fever, fatigue, and chest pains [3]. Regarding its overall effects on human health, LET was reported to possess potential efficacy that could be enhanced by advancing in combination with other chemotherapeutic agents [4][5][6][7].…”

Toward Rational Design of Novel Anti-Cancer Drugs Based on Targeting, Solubility, and Bioavailability Exemplified by 1,3,4-Thiadiazole Derivatives Synthesized Under Solvent-Free Conditions

“…Alginate is a biocompatible natural hydrophilic polysaccharide polymer isolated from marine brown algae. It has been reported that it increases the wettability of hydrophobic drug molecules [29,30], and accordingly, it has been used successful in delivering and encapsulating thiadiazole-based compounds [31,32,33,34]. Generally, the encapsulation of drugs with polymers is one of the versatile methods in controlling drug release over a long period of time and solves the complications related to traditional drug administration methods in chemotherapy.…”