Preparation, characterization and in vitro evaluation of ε-polylysine-loaded polymer blend microparticles for potential pancreatic cancer therapy

Abstract

Peptide active ingredients show great promise regarding the treatment of various health-endangering diseases. It is reported that L-lysine inhibits the proliferation of several tumour lines in vitro and in vivo. However, proteins and peptide drugs possess certain disadvantages such as in vivo instability and short biological half-life. On the grounds that drug delivery systems can overcome a wide spectrum of bioactive compounds issues, a biopolymeric blend-based microparticulated system capable of delivering ε-polylysine (PLL) was developed. PLL-loaded poly((L)Lactic acid)/poly(D,L-Lactide)-co-poly(ethylene glycol)-based microparticles (PLL-PB-MPs) were prepared and fully characterised exhibiting a narrow size distribution (1.2 ± 0.12 µm), high loading efficiency (81%) and improved thermal stability (T_d from 250 °C to 291 °C). The cytotoxicity and antiproliferative effect of PLL-PB-MPs in pancreatic adenocarcinoma cell lines BxPC3 and MIA PaCa-2 were confirmed. Due to their physicochemical and biopharmaceutical properties, PB-MPs constitute a promising carrier to deliver bioactive peptides.

Keywords:

• Biopolymers
• ε-polylysine
• microparticles
• polylactic acid

Acknowledgements

The authors thank GIHON Laboratorios Químicos SRL and LNK Chemsolutions LLC. Mónica C. Garcia thanks to CONICET for postdoctoral fellowship and to the Red de Macro Universidades de América Latina y el Caribe for the scholarship received. Merari T. Chevalier thanks to National University of Mar del Plata for her research fellowship.

Disclosure statement

The authors do not have any declarations of interest to report.

Additional information

Funding

This work was supported by Agencia Nacional de Promoción Científica y Tecnológica – Fondo para la investigación Científica y Tecnológica (PICT 3228); Consejo Nacional de Investigaciones Científicas y Técnicas de la República Argentina [Grant number: 0617] and Fundação de Amparo à Pesquisa do Estado de São Paulo [FAPESP, grant number 2010/52685-9].