title: Bioactive protein-based nanofibers interact with intestinal biological components resulting in transepithelial permeation of a therapeutic protein.
abstract: Proteins originating from natural sources may constitute a novel type of material for use in drug delivery. However, thorough understanding of the behavior and effects of such a material when processed into a matrix together with a drug is crucial prior to further development into a drug product. In the present study the potential of using bioactive electrospun fish sarcoplasmic proteins (FSP) as a carrier matrix for small therapeutic proteins was demonstrated in relation to the interactions with biological components of the intestinal tract. The inherent structural and chemical properties of FSP as a biomaterial facilitated interactions with cells and enzymes found in the gastrointestinal tract and displayed excellent biocompatibility. More specifically, insulin was efficiently encapsulated into FSP fibers maintaining its conformation, and subsequent controlled release was obtained in simulated intestinal fluid. The encapsulation of insulin into FSP fibers provided protection against chymotrypsin degradation, and resulted in an increase in insulin transport to around 12% without compromising the cellular viability. This increased transport was driven by interactions upon contact between the nanofibers and the Caco-2 cell monolayer leading to the opening of the tight junction proteins. Overall, electrospun FSP may constitute a novel material for oral delivery of biopharmaceuticals.
authors: Nano-BioScience Research Group, DTU-Food, Technical University of Denmark, Søltofts Plads, B227, DK-2800 Kgs. Lyngby, Denmark; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors: Karen
authors: K
authors: Stephansen
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors: María
authors: M
authors: García-Díaz
authors: Nano-BioScience Research Group, DTU-Food, Technical University of Denmark, Søltofts Plads, B227, DK-2800 Kgs. Lyngby, Denmark.
authors: Flemming
authors: F
authors: Jessen
authors: Nano-BioScience Research Group, DTU-Food, Technical University of Denmark, Søltofts Plads, B227, DK-2800 Kgs. Lyngby, Denmark. Electronic address: ioach@food.dtu.dk.
authors: Ioannis S
authors: IS
authors: Chronakis
authors: Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark. Electronic address: hanne.morck@sund.ku.dk.
authors: Hanne Mørck
authors: HM
authors: Nielsen
mesh_terms: D001826:Body Fluids / Q000737:chemistry / Q000378:metabolism; D018938:Caco-2 Cells; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004355:Drug Stability; D004847:Epithelial Cells / Q000378:metabolism*; D029941:Fish Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D057139:Nanofibers / Q000008:administration & dosage* / Q000737:chemistry*; D010539:Permeability; D017434:Protein Structure, Tertiary
chemical_list: D029941:Fish Proteins; D007328:Insulin
keywords: Electrospinning; Insulin; Intestinal delivery; Oral drug delivery; Protein