Development of the technology for obtaining PLGA and dipropoxybateriopurpurinimide-based nanoparticles. Evaluation of physicochemical and biological properties of the obtained delivery system

Abstract

The article describes the process of developing a technology for producing nanoparticles based on a copolymer of lactic and glycolic acids (PLGA) containing dipropoxybacteriopurpurinimide (DPBPI) for photodynamic therapy of malignant tumors of various origins. Technological parameters for optimizing the method in order to obtain nanoparticles with specified characteristics are presented in this paper. As a result, the nanoparticles sample with an average particle diameter of 222.6±2.8 nm; ξ-potential 26.3±4.61 mV; polydispersity index 0.144; the total content of DPBPI in PLGA-DPBPI nanoparticles 13.6% were obtained. In accordance with the developed technique, the batch of PLGA-DPBPI nanoparticles was developed for further biological studies. In vitro experiments on A549 human non-small cell lung carcinoma for DPBPI, delivered as a part of PLGA-DPBPI nanoparticles, and an EL cremophor-based emulsion (CrEL-DPBPI) showed a similar intracellular distribution (concentrated in vesicular cell structures and diffusely distributed in cytoplasm), as well as high photo induced activity and the absence of dark cytotoxicity in case of PLGA-DPBPI nanoparticles. The study of the PLGA-DPBPI nanoparticles specific activity in vivo on the S37 mouse soft tissue sarcoma model showed the selective accumulation of DPBPI in tumor tissue and the almost complete elimination of DPBPI from the body within 48 hours, as well as significant antitumor efficacy in PDT.

Keywords

• фотодинамическая терапия
• наночастицы
• plga
• фотосенсибилизатор
• фотоиндуцированная активность
• фотоиндуцированная противоопухолевая эффективность
• дипропоксибактериопурпуринимид