Synthesis, characterization, drug-loading capacity and safety of novel pH-independent amphiphilic amino acid copolymer micelles

Pharmazie. 2012 Sep;67(9):756-64.

Abstract

A novel block copolymer containing two polymeric components, poly(L-aspartic acid)-b-poly (L-phenylalanine) (PAA-PPA), was synthesized and its potential for the preparation of copolymer micelles with a poorly water-soluble drug was investigated in this study. The chemical structure and physical properties of PAA-PPA were characterized by FTIR, 1H NMR and TG. The degree of polymerization of PAA-PPA was calculated by analyzing the relative area of N-CH signal and C-CH3 of 1H NMR spectra. The critical micelle concentration (CMC) of the PAA-PPA achieved a minimum of 11.1 mg/L. Studies on the drug-free PAA-PPA solutions showed PAA-PPA aggregation into micellar type in the sub-150 nm size range. Furthermore, the size of the PAA-PPA micelles was found to be pH-independent between the pH range of 4.0 and 8.0, which could be favorable to avoid the limitation of the size change at the specified pH value seeking drug stability. 4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was studied as a poorly water-soluble model drug. The drug-loading and entrapment efficiency of the ATPR-loaded PAA-PPA micelles were 30.9 wt% and 87.9 %, respectively. The high drug-loading and entrapment efficiency were due to the synergistic effect of the micellar encapsulation and the binding interaction between drug and PAA-PPA. The ATPR-loaded PAA-PPA micelles showed a narrow size distribution, low zeta potential, high drug-loading capacity and good stable. The PAA-PPA was safer than Tween-80 and Cremophor EL (CrmEL) as an injectable pharmaceutical adjuvant for ATPR as indicated by the hemolysis and cytotoxicity studies. The novel amphiphilic amino acid copolymer can be considered as a prospective injectable delivery system for ATPR in terms of the pH-independent, greater drug-loading capacity and safety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry*
  • Animals
  • Cell Line
  • Cell Survival / drug effects
  • Drug Carriers / chemistry*
  • Drug Delivery Systems
  • Drug Stability
  • Electrochemistry
  • Hemolysis / drug effects
  • Hot Temperature
  • Humans
  • In Vitro Techniques
  • Indicators and Reagents
  • Micelles
  • Molecular Weight
  • Particle Size
  • Peptides / chemistry
  • Polymers / chemistry*
  • Rabbits
  • Solubility

Substances

  • Amino Acids
  • Drug Carriers
  • Indicators and Reagents
  • Micelles
  • Peptides
  • Polymers
  • polyaspartate
  • polyphenylalanine