(675e) Controlled Microfluidic Synthesis of Polymeric Nanoparticles for Drug Delivery

Polymeric nanoparticles (NPs) are versatile and effective drug delivery systems (DDS) that can be synthesized by bulk mixing and nanoprecipitation.¹ Despite the technological advancement in the design of these nanoformulated therapeutics, their translation into clinical products has been limited by poor control and limited scalability of their synthesis.^2,3 To date, formulation of nanotherapeutics has been driven primarily by empirical approaches. For improved translation of this class of DDS, the need for controlled and scalable synthesis led to the development of hydrodynamic flow focusing devices and coaxial jet mixers.^4,5 The NP production rate of these devices is either in the μg min^-1 or in the g min^-1 scale. To bridge this throughput gap, in this work, we have engineered a versatile and robust coaxial jet mixer for NP synthesis that can be used for rapid screening and for scale-up production of NPs. In total, the device provided NPs of tunable size, process scalability, formulation screening, and insights into the physical driving forces of polymeric nanocarrier assembly.

The coaxial jet mixer was used to synthesize poly(ethylene glycol)-b-poly(lactide) (PEG-b-PLA) NPs in various solvents. The resulting NP size was controlled between 40 and 140 nm by tuning flow conditions and solvent. Process scale-up lead to NP production rates of up to 175 mg min^-1 under stable operation. A model drug, Indomethacin, was encapsulated within PEG-b-PLA NPs at drug loadings that were comparable to standard batch nanoprecipitation but with a smaller diameter and more narrow polydispersity. A unique advantage of the coaxial jet mixer was the ability to rapidly screen formulation conditions, which enabled new insights into the effect of solvent on nanoparticle formation.

Overall, this presentation will present a versatile and robust device for NP synthesis while providing fundamental insights on engineering efficient nanoformulations.

References:

1 Kamaly, N., Xiao, Z., et al. Chem. Soc. Rev. 41, 2971–3010, (2012)
2 Shi, J. et al. Nat. Rev. Cancer 17, 20–37, (2017)
3 Hickey, J. W. et al. J. Control. Release 219, 535–547, (2015)
4 Lim, J.-M. et al. ACS Nano 8, 6056–6065, (2014)
5 Karnik, R., Gu, F. et al. Nano Lett. 8, 2906–2912, (2008)