title: Production methods and stabilization strategies for polymer-based nanoparticles and microparticles for parenteral delivery of peptides and proteins.
abstract: BACKGROUND
  Therapeutic proteins and peptides often require parenteral administration, which compels frequent administration and patient discomfort. This ultimately decreases compliance and leads to therapy failure. Biocompatible and biodegradable polymers offer a versatile matrix for particles suitable for the parenteral delivery of these biomacromolecules, with the added possibility of long-term controlled release. During the past decade, research on polymeric microparticles and nanoparticles as delivery vehicles has intensified; nevertheless, only few products have been commercialized.
  
  
  METHODS
  This review discusses the different production techniques for microparticles and nanoparticles suitable for peptide and protein delivery, including examples of recently developed formulations. Stability of the biomacromolecules related to these production techniques is evaluated, as it is a critical parameter to be considered during product development. Additionally, several strategies to improve stability are described in detail, providing insight and guidance for further formulation development.
  
  
  CONCLUSIONS
  In the conventionally used and thoroughly investigated emulsification method, stability of peptides and proteins is still a challenge. Emerging methods like solvent displacement, layer-by-layer polymer deposition, electrospraying and supercritical fluid technologies have the potential to improve stability of the protein and peptide. Nonetheless, these methods are still under development and they need critical evaluation to improve production efficiency before proceeding to in vivo efficacy studies. Improvement should be achieved by strengthening cooperation between academic research groups, pharmaceutical companies and regulatory authorities.
authors.affiliation: University of Groningen, Department of Pharmaceutical Technology and Biopharmacy , Antonius Deusinglaan 1, Groningen , Netherlands p.olinga@rug.nl.
authors.forename: Naomi
authors.initials: N
authors.lastname: Teekamp
authors.forename: Luisa F
authors.initials: LF
authors.lastname: Duque
authors.forename: Henderik W
authors.initials: HW
authors.lastname: Frijlink
authors.forename: Wouter L J
authors.initials: WL
authors.lastname: Hinrichs
authors.forename: Peter
authors.initials: P
authors.lastname: Olinga
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods; D005079:Excipients / Q000737:chemistry; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000008:administration & dosage*; D011108:Polymers / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage*; D012997:Solvents / Q000737:chemistry
chemical_list: D005079:Excipients; D010455:Peptides; D011108:Polymers; D011506:Proteins; D012997:Solvents
keywords: formulation development; microparticles; nanoparticles; peptide delivery; peptide stability; polymer; protein delivery; protein stability; sustained release