Synthesis of a novel PEG-block-poly(aspartic acid-stat-phenylalanine) copolymer shows potential for formation of a micellar drug carrier

Int J Pharm. 2005 Jun 13;297(1-2):242-53. doi: 10.1016/j.ijpharm.2005.02.025. Epub 2005 Apr 25.

Abstract

A novel functionalised copolymer with three polymeric components, poly(ethylene glycol)-block-poly(aspartic acid-stat-phenylalanine), PEG-P(asp-phe), was synthesised and investigated for its potential to form micelles via ionic interactions with a model water-soluble drug, diminazene aceturate. Drug-free solutions of structurally related PEG-P(asp-phe) 5:6:4 and PEG-P(asp-phe) 5:4:6 copolymers indicated polymeric aggregation into micellar-type constructs. The size of PEG-P(asp-phe) 5:6:4 micelles was found to be pH and drug content-dependent. The drug-loaded systems existed as discreet units and were fairly uniform in size and shape. More drug could be included in the PEG-P(asp-phe) 5:6:4 micelles as compared to if only interaction with carboxyl groups from aspartic acid units was responsible for micelle formation, indicating the augmentative role of phenylalanine moieties in drug-incorporation. The slower in vitro drug release from PEG-P(asp-phe) 5:6:4 micelles as compared to PEG-Pasp (AB) micelles indicated the role of the phenylalanine moiety in controlling drug release. This study, therefore, confirmed the potential of a novel tri-component copolymer structure, PEG-P(asp-phe), for the formation of polyionic micelles for drug delivery.

MeSH terms

  • Chemical Phenomena
  • Chemistry, Physical
  • Delayed-Action Preparations
  • Diminazene / administration & dosage
  • Diminazene / analogs & derivatives
  • Diminazene / chemistry
  • Drug Carriers / chemical synthesis*
  • Drug Carriers / chemistry
  • Drug Delivery Systems
  • Indicators and Reagents
  • Micelles*
  • Microscopy, Electron, Transmission
  • Particle Size
  • Phenylalanine / chemistry
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / chemistry
  • Scattering, Radiation

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Indicators and Reagents
  • Micelles
  • polyethylene glycol-block-polyaspartic acid
  • Polyethylene Glycols
  • Phenylalanine
  • diminazene aceturate
  • Diminazene