Long-term delivery of protein therapeutics

Expert Opin Drug Deliv. 2015 Mar;12(3):415-40. doi: 10.1517/17425247.2015.961420. Epub 2014 Sep 24.

Abstract

Introduction: Proteins are effective biotherapeutics with applications in diverse ailments. Despite being specific and potent, their full clinical potential has not yet been realized. This can be attributed to short half-lives, complex structures, poor in vivo stability, low permeability, frequent parenteral administrations and poor adherence to treatment in chronic diseases. A sustained release system, providing controlled release of proteins, may overcome many of these limitations.

Areas covered: This review focuses on recent development in approaches, especially polymer-based formulations, which can provide therapeutic levels of proteins over extended periods. Advances in particulate, gel-based formulations and novel approaches for extended protein delivery are discussed. Emphasis is placed on dosage form, method of preparation, mechanism of release and stability of biotherapeutics.

Expert opinion: Substantial advancements have been made in the field of extended protein delivery via various polymer-based formulations over last decade despite the unique delivery-related challenges posed by protein biologics. A number of injectable sustained-release formulations have reached market. However, therapeutic application of proteins is still hampered by delivery-related issues. A large number of protein molecules are under clinical trials, and hence, there is an urgent need to develop new methods to deliver these highly potent biologics.

Keywords: formulation; hydrogel; implant; microparticle; nanoparticle; protein delivery; release mechanism; stability; sustained release; thermosensitive gel.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Biological Products / administration & dosage*
  • Biological Products / pharmacokinetics
  • Chemistry, Pharmaceutical
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Drug Implants / administration & dosage
  • Drug Implants / pharmacokinetics
  • Drug Liberation
  • Drug Stability
  • Gels / chemistry*
  • Hydrogen-Ion Concentration
  • Microspheres
  • Nanoparticles / chemistry
  • Peptides / administration & dosage
  • Peptides / pharmacokinetics
  • Polymers / chemistry*
  • Proteins / administration & dosage*
  • Proteins / pharmacokinetics

Substances

  • Biological Products
  • Delayed-Action Preparations
  • Drug Implants
  • Gels
  • Peptides
  • Polymers
  • Proteins