title: 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.
authors.affiliation: Department of Chemical and Biological Engineering and §Department of Molecular Biology, Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Nikolas T
authors.initials: NT
authors.lastname: Weissmueller
authors.affiliation: Department of Chemical and Biological Engineering and §Department of Molecular Biology, Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Hoang D
authors.initials: HD
authors.lastname: Lu
authors.affiliation: Department of Chemical and Biological Engineering and §Department of Molecular Biology, Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Amanda
authors.initials: A
authors.lastname: Hurley
authors.affiliation: Department of Chemical and Biological Engineering and §Department of Molecular Biology, Princeton University , Princeton, New Jersey 08544, United States.
authors.forename: Robert K
authors.initials: RK
authors.lastname: Prud'homme
mesh_terms: D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology; D002364:Caseins / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010316:Particle Size; D011355:Prodrugs / Q000737:chemistry / Q000494:pharmacology; D053038:Quorum Sensing / Q000187:drug effects; D014810:Vitamin E / Q000737:chemistry; D003313:Zea mays / Q000737:chemistry; D015028:Zein / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D002364:Caseins; D004337:Drug Carriers; D011355:Prodrugs; D014810:Vitamin E; D015028:Zein