Efficacy assessment of self-assembled PLGA-PEG-PLGA nanoparticles: Correlation of nano-bio interface interactions, biodistribution, internalization and gene expression studies

• Published in: International journal of pharmaceutics Vol. 533; no. 2; pp. 389 - 401
• Main Authors: Dimchevska, Simona, Geskovski, Nikola, Koliqi, Rozafa, Matevska-Geskovska, Nadica, Gomez Vallejo, Vanessa, Szczupak, Boguslaw, Sebastian, Eneko San, Llop, Jordi, Hristov, Delyan R., Monopoli, Marco P., Petruševski, Gjorgji, Ugarkovic, Sonja, Dimovski, Aleksandar, Goracinova, Katerina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30-11-2017
• Subjects: 7-Ethyl-10-hydroxycamptotecin (SN-38); Adsorption; Animals; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacokinetics; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Camptothecin - chemistry; Camptothecin - pharmacokinetics; Cell Cycle Proteins - genetics; Cell Line, Tumor; Fibroblast Growth Factor 3 - genetics; Gene expression; Gene Expression Regulation, Neoplastic - drug effects; Histones - genetics; Humans; Irinotecan; Molecular Weight; Muscle Proteins - genetics; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Nanoprecipitation; Nano–bio interface interactions; Nerve Tissue Proteins - genetics; Particle Size; PLGA-PEG-PLGA/PEO-PPO-PEO; Polyethylene Glycols - administration & dosage; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacokinetics; Polyglactin 910 - administration & dosage; Polyglactin 910 - chemistry; Polyglactin 910 - pharmacokinetics; Polymeric nanoparticles; Rats, Wistar; Serum Albumin, Bovine - chemistry; Surface Properties; Tissue Distribution; Ubiquitins - genetics; 7-Ethyl-10-hydroxycamptotecin (SN-38); PLGA-PEG-PLGA/PEO-PPO-PEO; Polymeric nanoparticles; Nanoprecipitation; Nano–bio interface interactions; Gene expression
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2017.05.054

[Display omitted]
The aim of our study was to develop and compare the biological performance of two types of biodegradable SN-38 loaded nanoparticles (NPs) with various surface properties, composed of low and high Mw triblock PLGA-PEG-PLGA copolymers, applying rational quality and safety by design approach. Therefore, along with the optimization of crucial physico-chemical properties and in order to evaluate the therapeutical potential and biocompatibility of prepared polymeric nanoparticles, analysis of nano-bio interactions, cell internalization, gene expression and biodistribution studies were performed.
The optimized formulations, one of low Mw and one composed of high Mw PLGA-PEG-PLGA copolymer, exhibited different characteristics in terms of surface properties, particle size, zeta potential, drug loading, protein adsorption and biodistribution, which may be attributed to the variations in nano–bio interface interactions due to different NP building blocks length and Mw. On the contrary to protein adsorption and biodistribution studies, both types of NPs exhibited similar results during cell internalization and gene expression studies performed in cell culture medium containing serum proteins.
This pool of useful data for internalization and efficacy as well as the notable advance in the circulation time of low Mw NPs may be further employed for shaping the potential of the designed nanocarriers.