Abstract
Emulsification-diffusion method is often used to produce polymeric nanoparticles. However, their numerous and/or lengthy steps make it difficult to use widely. Thus, a modified method using solvent blends (miscible/partially miscible in water, 25–100%) as the organic phases to overcome these disadvantages and its design space were investigated. To further simplify the process, no organic/aqueous phase saturation and no water addition after the emulsification step were performed. Biodegradable (PLGA) or pH-sensitive (Eudragit® E100) nanoparticles were robustly produced using low/medium shear stirring adding dropwise the organic phase into the aqueous phase or vice versa. Several behaviors were also obtained: lowering the partially water-miscible solvent ratio relative to the organic phase or the poloxamer-407 concentration; or increasing the organic phase polarity or the polyvinyl alcohol concentration produced smaller particle sizes/polydispersity. Nanoparticle zeta potential increased as the water-miscible solvent ratio increased. Poloxamer-407 showed better performance to decrease the particle size (~50 nm) at low concentrations (≤1%, w/v) compared with polyvinyl alcohol at 1–5% (w/v), but higher concentrations produced bigger particles/polydispersity (≥600 nm). Most important, an inverse linear correlation to predict the particle size by determining the solubility parameter was found. A rapid method to broadly prepare nanoparticles using straightforward equipment is provided.
Highlights
Publisher’s Note: MDPI stays neutralEmulsification-solvent diffusion method is able to produce polymeric nanoparticles (NPs) with high yields, no need of high shear stirring or ultrasonication, batch-to-batch reproducibility and good encapsulation efficiencies [1,2]
The organic phase (OP) consisted of partially water-miscible solvents and water-miscible solvents varying their ratios in order to produce nanoparticles of 50 ≤ 1000 nm, using either low or high shear stirring (1500–8000 rpm) from straightforward equipment
Design 2 and 6; Figures 2a–c, 3a and 6b). This agrees with the results found in another compared with methylene chloride by emulsificationstudy using the blend chloroform:ethanol as OP and the emulsification-diffusion process evaporation [16] and emulsion–diffusion-evaporation methods [11]
Summary
Emulsification-solvent diffusion method is able to produce polymeric nanoparticles (NPs) with high yields, no need of high shear stirring or ultrasonication, batch-to-batch reproducibility and good encapsulation efficiencies [1,2]. Numerous and long steps involved to pre-saturate the solvents and to eliminate higher volumes of water from the final dispersion make it difficult to use as a feasible method for many applications. The tunability or range of particles sizes produced from the few partially miscible solvents is limited [3]. Modifications of this method are proposed in an attempt to overcome those disadvantages. Methods to produce NPs involve two main strategies, the use of preformed polymers or the polymerization process using monomers [5]. Preformed polymers are preferred because of the low toxicity compared with regard to jurisdictional claims in published maps and institutional affiliations
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