title: Long-term delivery of protein therapeutics.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University of Missouri-Kansas City, Pharmaceutical Sciences , Kansas City, MO , USA mitraa@umkc.edu.
authors.forename: Ravi
authors.initials: R
authors.lastname: Vaishya
authors.forename: Varun
authors.initials: V
authors.lastname: Khurana
authors.forename: Sulabh
authors.initials: S
authors.lastname: Patel
authors.forename: Ashim K
authors.initials: AK
authors.lastname: Mitra
mesh_terms: D001688:Biological Products / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004343:Drug Implants / Q000008:administration & dosage / Q000493:pharmacokinetics; D065546:Drug Liberation; D004355:Drug Stability; D005782:Gels / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D008863:Microspheres; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D001688:Biological Products; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005782:Gels; D010455:Peptides; D011108:Polymers; D011506:Proteins
keywords: formulation; hydrogel; implant; microparticle; nanoparticle; protein delivery; release mechanism; stability; sustained release; thermosensitive gel