title: Food Protein Based Core-Shell Nanocarriers for Oral Drug Delivery: Effect of Shell Composition on in Vitro and in Vivo Functional Performance of Zein Nanocarriers.
abstract: The study was aimed at systematically investigating the influence of shell composition on the particle size, stability, release, cell uptake, permeability, and in vivo gastrointestinal distribution of food protein based nanocarriers for oral delivery applications. Three different core-shell nanocarriers were prepared using food-grade biopolymers including zein-casein (ZC) nanoparticles, zein-lactoferrin (ZLF), nanoparticles and zein-PEG (ZPEG) micelles. Nile red was used as a model hydrophobic dye for in vitro studies. The nanocarriers had negative, positive, and neutral charge, respectively. All three nanocarriers had a particle size of less than 200 nm and a low polydispersity index. The nanoparticles were stable at gastrointestinal pH (2-9) and ionic strength (10-200 mM). The nanocarriers sustained the release of Nile red in simulated gastric and intestinal fluids. ZC nanoparticles showed the slowest release followed by ZLF nanoparticles and ZPEG micelles. The nanocarriers were taken up by endocytosis in Caco-2 cells. ZPEG micelles showed the highest cell uptake and transepithelial permeability followed by ZLF and ZC nanoparticles. ZPEG micelles also showed P-gp inhibitory activity. All three nanocarriers showed bioadhesive properties. Cy 5.5, a near IR dye, was used to study the in vivo biodistribution of the nanocarriers. The nanocarriers showed longer retention in the rat gastrointestinal tract compared to the free dye. Among the three formulations, ZC nanoparticles was retained the longest in the rat gastrointestinal tract (≥24 h). Overall, the outcomes from this study demonstrate the structure-function relationship of core-shell protein nanocarriers. The findings from this study can be used to develop food protein based oral drug delivery systems with specific functional attributes.
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Alqahtani
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: M Saiful
authors.initials: MS
authors.lastname: Islam
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Satheesh
authors.initials: S
authors.lastname: Podaralla
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Radhey S
authors.initials: RS
authors.lastname: Kaushik
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Joshua
authors.initials: J
authors.lastname: Reineke
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Tofuko
authors.initials: T
authors.lastname: Woyengo
authors.affiliation: Department of Pharmaceutical Sciences, ∥Department of Biology and Microbiology/Veterinary and Biomedical Sciences, and ⊥Department of Animal Science, South Dakota State University , Brookings, South Dakota 57007, United States.
authors.forename: Omathanu
authors.identifier: 0000-0001-8645-0878
authors.initials: O
authors.lastname: Perumal
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005260:Female; D005502:Food; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008807:Mice, Inbred BALB C; D008823:Micelles; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution / Q000187:drug effects; D015028:Zein / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008823:Micelles; D011506:Proteins; D011092:Polyethylene Glycols; D015028:Zein
keywords: casein; core−shell nanocarriers; food proteins; lactoferrin; oral delivery; zein