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. 2019 Aug 27;11(9):1406.
doi: 10.3390/polym11091406.

Rapid, Single-Step Protein Encapsulation via Flash NanoPrecipitation

Shani L Levit  1 , Rebecca C Walker  1 , Christina Tang  2
Affiliations

Rapid, Single-Step Protein Encapsulation via Flash NanoPrecipitation

Shani L Levit et al. Polymers (Basel). .

Abstract

Flash NanoPrecipitation (FNP) is a rapid method for encapsulating hydrophobic materials in polymer nanoparticles with high loading capacity. Encapsulating biologics such as proteins remains a challenge due to their low hydrophobicity (logP < 6) and current methods require multiple processing steps. In this work, we report rapid, single-step protein encapsulation via FNP using bovine serum albumin (BSA) as a model protein. Nanoparticle formation involves complexation and precipitation of protein with tannic acid and stabilization with a cationic polyelectrolyte. Nanoparticle self-assembly is driven by hydrogen bonding and electrostatic interactions. Using this approach, high encapsulation efficiency (up to ~80%) of protein can be achieved. The resulting nanoparticles are stable at physiological pH and ionic strength. Overall, FNP is a rapid, efficient platform for encapsulating proteins for various applications.

Keywords: Flash NanoPrecipitation; electrostatic interactions; nanoparticles; polyethylenimine; protein encapsulation; self-assembly; tannic-acid.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Dynamic light scattering (DLS) intensity weighted size distribution results of (A) bovine serum albumin-tannic acid (BSA-TA) complex without the presence of a stabilizer, (B) BSA-TA complex with an amphiphilic block copolymer, and (C) the BSA-TA complex stabilized with 750kDa polyethylenimine (PEI), immediately upon mixing and after 24 h. The BSA-TA complex stabilized with PEI did not change in size after 24 h.
Figure 2
Figure 2
Schematic of the proposed self-assembly mechanisms using 750 kDa and 10 kDa polyethylenimine (PEI) via flash nanoprecipitation (FNP) with PEI stabilizer. In the confined impinging jet (CIJ) mixer the bovine serum albumin (BSA) and tannic acid (TA) interact via hydrogen bonding to form an insoluble complex. Then the complex is immediately diluted in a reservoir containing PEI. The BSA-TA complex interacts with the PEI via electrostatic interaction. High molecular weight 750 kDa PEI aggregates template nanoparticle assembly and absorb the BSA-TA precipitate. In contrast, 10 kDa PEI adsorbs on the precipitating BSA-TA complex forming a core-shell structure.
Figure 3
Figure 3
Effect of nanoparticle dispersion pH on size for (A) 10 kDa polyethylenimine nanoparticles (PEI NPs) and (B) 750 kDa PEI NPs. The size of the particles was measured 24 h after adjusting the pH. The 10 kDa PEI NPs destabilized under acidic conditions and released bovine serum albumin (BSA). The 750 kDa PEI NPs did not change size at acidic pH.
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