Flash NanoPrecipitation for the Encapsulation of Hydrophobic and Hydrophilic Compounds in Polymeric Nanoparticles

Abstract

The formulation of a therapeutic compound into nanoparticles (NPs) can impart unique properties. For poorly water-soluble drugs, NP formulations can improve bioavailability and modify drug distribution within the body. For hydrophilic drugs like peptides or proteins, encapsulation within NPs can also provide protection from natural clearance mechanisms. There are few techniques for the production of polymeric NPs that are scalable. Flash NanoPrecipitation (FNP) is a process that uses engineered mixing geometries to produce NPs with narrow size distributions and tunable sizes between 30 and 400 nm. This protocol provides instructions on the laboratory-scale production of core-shell polymeric nanoparticles of a target size using FNP. The protocol can be implemented to encapsulate either hydrophilic or hydrophobic compounds with only minor modifications. The technique can be readily employed in the laboratory at milligram scale to screen formulations. Lead hits can directly be scaled up to gram-and kilogram-scale. As a continuous process, scale-up involves longer mixing process run time rather than translation to new process vessels. NPs produced by FNP are highly loaded with therapeutic, feature a dense stabilizing polymer brush, and have a size reproducibility of ± 6%. Video Link The video component of this article can be found at https://www.jove.com/video/58757/ 13. Nucleation occurs uniformly in the mixing chamber and particle growth proceeds until halted by the assembly of the BCP onto the surface 9,14. The mixed stream containing stable particles may then be diluted with additional antisolvent to suppress Ostwald ripening of the particles 15,16,17 .

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

“…12 The potential benets of encapsulationtargeting, protection from enzymatic degradation, improved circulation time, enhanced bioavailability, controlled release, reduced toxicity, and overall improved drug performanceare strong driving motivations to develop scalable, highly-loaded formulations with high encapsulation efficiencies. 13,14 This is particularly attractive for biologic (peptide and protein) therapeutics, whose circulation time unprotected in the blood may be as low as minutes. 12 Nanoparticle formulation strategies for hydrophobic drugs have been developed to address the growing number of new, strongly hydrophobic therapeutics.…”

Antioxidant Nanoparticles for Concerted Inhibition of α-Synuclein Fibrillization, and Attenuation of Microglial Intracellular Aggregation and Activation

“…Briefly, shell and core molecules were dissolved in DMSO at varying concentrations and were mixed at 50/50 % (v/v) ratio in a final volume of 500 µL. A confined impinging jet mixer was used to rapidly mix an aqueous water stream and organic phase stream containing shell and core molecules (Markwalter et al, 2019). The exit stream was collected in 9× volume of water and the nanoparticles were dialyzed against water using a 3.5 kDa MW cutoff dialysis cassette.…”

Translational formulation of nanoparticle therapeutics from laboratory discovery to clinical scale

“…1). The confined impinging jet mixer (CIJ) can be used in a batch, hand-held mode with syringes to feed the device, which produces NP formulations with sub-milligram active pharmaceutical ingredient (API) requirements [22]. The CIJ can also be driven by syringe pumps to make samples with larger volume of 200–300 mL [10].…”