Preparation of All-Trans-Retinoic Acid-Loaded mPEG-PLGA Nanoparticles Using Microfluidic Flow-Focusing Device for Controlled Drug Delivery.

In recent years, microfluidic devices present unique advantages for the development of a new generation of nanoparticle synthesis method compared to bulk methods. In this study, we report a microfluidic flow-focusing method for the production of all trans retinoic acid (ATRA)-loaded methoxy poly(ethylene glycol)-poly(lactide-coglycolide) (mPEG-PLGA) nanoparticles (NPs). Box–Behnken experimental design (BBD) was applied to optimize of formulation ingredients and process conditions with minimum particle size, maximum drug loading% (DL%) and encapsulation efficiency% (EE%). Polymer concentration, drug concentration and flow rates of solvent (S) and antisolvent (AS) were selected as independent variables. Based on optimization strategy, minimum particle size achieved shows average (SD) particle size of 1 5 9 ± 8 nm with DL of 7. 1 ± 0. 0 4 wt.% and EE of 9 8. 7 1 ± 0. 5 8 wt.%, respectively. While maximum DL has been reported to be 1 6. 5 1 ± 0. 0 3 wt.% with particle size of 2 0 5 ± 5. 2 9 nm and EE of 9 9. 4 2 ± 0. 4 5 wt.%, respectively. Moreover, the results have shown that the AS/S ratio represents the most significant effect on particle size. Indeed, increasing the AS flow rate directly results in generating smaller particles. The AS/S ratio represents the least significant effect on DL%, such that, at fixed flow rates, higher DL was observed at high concentration of drug and lower concentration of polymer. In conclusion, optimization of the ATRA-loaded mPEG-PLGA NPs by BBD yielded in a favorable drug carrier for ATRA that could provide a new treatment modality for different malignancies. A transparent t-shaped microfluidic device consists of three inlets and one main mixing outlet channel was designed and constructed using glass wafer in order to synthesize ATRA loaded mPEG-PLGA nanoparticles. The influence of flow rate ratio, polymer concentration, and drug concentration on the nanoparticles' size has been investigated. An optimized ATRA loaded mPEG-PLGA NPs could provide a new treatment modality for different malignancies. [ABSTRACT FROM AUTHOR]

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