Protein-loaded emulsion electrospun fibers optimized for bioactivity retention and pH-controlled release for peroral delivery of biologic therapeutics

Int J Pharm. 2017 Nov 25;533(1):99-110. doi: 10.1016/j.ijpharm.2017.09.043. Epub 2017 Sep 21.

Abstract

Biologics are the most rapidly growing class of therapeutics, but commonly suffer from low stability. Peroral administration of these therapeutics is an attractive delivery route; however, this route introduces unique physiological challenges that increase the susceptibility of proteins to lose function. Formulation of proteins into biomaterials, such as electrospun fibers, is one strategy to overcome these barriers, but such platforms need to be optimized to ensure protein stability and maintenance of bioactivity during the formulation process. This work develops an emulsion electrospinning method to load proteins into Eudragit® L100 fibers for peroral delivery. Horseradish peroxidase and alkaline phosphatase are encapsulated with high efficiency into fibers and released with pH-specificity. Recovery of protein bioactivity is enhanced through reduction of the emulsion aqueous phase and the inclusion of a hydrophilic polymer excipient. Finally, we show that formulation of proteins in lyophilized electrospun fibers extends the therapeutic shelf life compared to aqueous storage. Thus, this platform shows promise as a novel dosage form for the peroral delivery of biotherapeutics.

Keywords: Controlled release; Emulsion electrospinning; Nanofibers; Peroral drug delivery; Protein delivery.

MeSH terms

  • Administration, Oral
  • Alkaline Phosphatase / chemistry*
  • Biological Products / chemistry
  • Drug Delivery Systems*
  • Drug Liberation
  • Emulsions
  • Freeze Drying
  • Horseradish Peroxidase / chemistry*
  • Hydrogen-Ion Concentration
  • Nanofibers / chemistry*
  • Polymethacrylic Acids / chemistry

Substances

  • Biological Products
  • Emulsions
  • Polymethacrylic Acids
  • methylmethacrylate-methacrylic acid copolymer
  • Horseradish Peroxidase
  • Alkaline Phosphatase