Formulation of tunable size PLGA-PEG nanoparticles for drug delivery using microfluidic technology

Abstract

Amphiphilic block co-polymer nanoparticles are interesting candidates for drug delivery as a result of their unique properties such as the size, modularity, biocompatibility and drug loading capacity. They can be rapidly formulated in a nanoprecipitation process based on self-assembly, resulting in kinetically locked nanostructures. The control over this step allows us to obtain nanoparticles with tailor-made properties without modification of the co-polymer building blocks. Furthermore, a reproducible and controlled formulation supports better predictability of a batch effectiveness in preclinical tests. Herein, we compared the formulation of PLGA-PEG nanoparticles using the typical manual bulk mixing and a microfluidic chip-assisted nanoprecipitation. The particle size tunability and controllability in a hydrodynamic flow focusing device was demonstrated to be greater than in the manual dropwise addition method. We also analyzed particle size and encapsulation of fluorescent compounds, using the common bulk analysis and advanced microscopy techniques: Transmission Electron Microscopy and Total Internal Reflection Microscopy, to reveal the heterogeneities occurred in the formulated nanoparticles. Finally, we performed in vitro evaluation of obtained NPs using MCF-7 cell line. Our results show how the microfluidic formulation improves the fine control over the resulting nanoparticles, without compromising any appealing property of PLGA nanoparticle. The combination of microfluidic formulation with advanced analysis methods, looking at the single particle level, can improve the understanding of the NP properties, heterogeneities and performance.

A Novel Sustained Anti-Inflammatory Effect of Atorvastatin—Calcium PLGA Nanoparticles: In Vitro Optimization and In Vivo Evaluation

“…PEG is nonionic polymer, universally employed during fabrication of NPs to enhance their residence time in blood circulation leading to achieve better absorption and hence enhanced pharmacokinetic properties of nano formulations [45]. There are different methods used to incorporate PEG into polymeric PLGA NPs.…”

“…There are different methods used to incorporate PEG into polymeric PLGA NPs. Chemically synthesized coblock polymers is the main approach [45] and also, physically comixing PLGA with PEG is considered a promising strategy which efficiently affects on NPs physicochemical features [12,19]. Here in this study, we added comixed PEG for surface modification because PEG could form a periphery layer surrounding NPs.…”

“…FTIR is as important analytical study should be fully investigated during NPs preparation to exclude any physical and chemical interaction might occur between the polymeric material and drug, also, to ensure the compatibility between all the components of NPs. FTIR aids to examine the effectiveness of drug encapsulation into polymeric core of NPs [7,45]. As illustrated in Section 3.3.1, FTIR spectrum of AT-Ca NPs shows no loss of the functional groups of free drug and native PLGA negating any chemical interaction occurred between the drug and polymer.…”

Recent Advances in the Surface Functionalization of PLGA-Based Nanomedicines

“…The monomer ratio is usually used to identify the polymer’s form. For example, PLGA 50:50, which is broadly employed in drug delivery [ 11 , 12 , 13 , 14 ], means a PLGA copolymer with 50% of LA and GA, respectively. The most common LA:GA ratios employed in research are 50:50, 65:35, 75:25 and 85:15 (LA:GA ratio) [ 15 ].…”

“…With the aim of enhancing the productivity, reproducibility, and scalability of PLGA NPs, several production methods, such microfluidic technology [ 12 ], supercritical fluid technology [ 47 ], and membrane-assisted strategies [ 48 ], have recently been investigated. Among these approaches, particle replication in non-wetting templates (PRINT), a soft lithography platform, enables the ability to control size and shape, independent of process variables, and the generation of truly monodisperse particles [ 49 ].…”