Nanocarriers from GRAS Zein Proteins to Encapsulate Hydrophobic Actives

Abstract

One factor limiting the expansion of nanomedicines has been the high cost of the materials and processes required for their production. We present a continuous, scalable, low cost nanoencapsulation process, Flash Nanoprecipitation (FNP) that enables the production of nanocarriers (NCs) with a narrow size distribution using zein corn proteins. Zein is a low cost, GRAS protein (having the FDA status of "Generally Regarded as Safe") currently used in food applications, which acts as an effective encapsulant for hydrophobic compounds using FNP. The four-stream FNP configuration allows the encapsulation of very hydrophobic compounds in a way that is not possible with previous precipitation processes. We present the encapsulation of several model active compounds with as high as 45 wt % drug loading with respect to zein concentration into ∼100 nm nanocarriers. Three examples are presented: (1) the pro-drug antioxidant, vitamin E-acetate, (2) an anticholera quorum-sensing modulator CAI-1 ((S)-3-hydroxytridecan-4-one; CAI-1 that reduces Vibrio cholerae virulence by modulating cellular communication), and (3) hydrophobic fluorescent dyes with a range of hydrophobicities. The specific interaction between zein and the milk protein, sodium caseinate, provides stabilization of the NCs in PBS, LB medium, and in pH 2 solutions. The stability and size changes in the three media provide information on the mechanism of assembly of the zein/active/casein NC.

Design and Solidification of Fast-Releasing Clofazimine Nanoparticles for Treatment of Cryptosporidiosis

“…31 Zein was dissolved at 6 mg/mL in 60% ethanol (EtOH) in DI water while NaCas was dissolved at 1 mg/mL in citrate buffer at pH 7.4 (10 mM sodium citrate, pH adjusted with citric acid). In addition, clofazimine was dissolved in acetone at 6 mg/mL.…”

Fabrication and Characterisation of a Photo-Responsive, Injectable Nanosystem for Sustained Delivery of Macromolecules

“…Zein is a cost-effective hydrophobic prolamin polymer extracted from maize that easily forms self-assembled spherical nanosized particles suitable as potential drug carriers. It is also biodegradable, non-toxic, biocompatible and considered generally recognised as safe (GRAS) [ 4 , 8 ]. An antioxidative property in zein resultant from its high aliphatic index, fatty acid content and surface hydrophobicity has been reported [ 9 ].…”

Single-Step Self-Assembly and Physical Crosslinking of PEGylated Chitosan Nanoparticles by Tannic Acid

“…For example, rapid mixing and precipitation reactions have been combined to produce lead sulfate nanoparticles stabilized by a chitosan shell [17]. Hydrophobic zein protein nanocarriers stabilized by casein have also been reported [18]. The zein defined the nanoparticle size and the particle was stabilized by casein interactions.…”