Encapsulation of the synthetic retinoids Am80 and LE540 into polymeric micelles and the retinoids' release control

J Control Release. 2009 Jun 19;136(3):187-95. doi: 10.1016/j.jconrel.2009.02.024. Epub 2009 Mar 14.

Abstract

The objective of this study was to encapsulate two synthetic retinoids Am80 and LE540 into polymeric micelles and to control the retinoids' release rate in vitro. Highly efficient encapsulation yields of these retinoids were obtained for micelles forming from PEG-poly(benzyl aspartate) block copolymers in the wide range of the benzyl substitution degree. The in vitro release examination for LE540 indicated very stable encapsulation of this retinoid owing to its strongly hydrophobic nature. On the other hand, Am80 exhibited a rapid release in Dulbecco's phosphate buffer saline. An addition of a hydrophobic alkyl amine in the Am80-encapsulation process successfully led to significant retardation of the Am80 release rate. A mechanism of the retardation was considered an increase of Am80 hydrophobicity due to an ion-pairing with the alkyl amine. This paper is the first report on release control in the polymeric micelle carrier system through the ion-pairing between an encapsulated drug and an additive.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspartic Acid / chemical synthesis
  • Aspartic Acid / chemistry*
  • Benzoates / chemistry*
  • Biopolymers / chemistry*
  • Delayed-Action Preparations / chemical synthesis
  • Delayed-Action Preparations / chemistry*
  • Dibenzazepines / chemistry*
  • Dimethylamines / chemistry
  • Excipients / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Micelles*
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry*
  • Retinoids / chemistry*
  • Solubility
  • Tetrahydronaphthalenes / chemistry*

Substances

  • Benzoates
  • Biopolymers
  • Delayed-Action Preparations
  • Dibenzazepines
  • Dimethylamines
  • Excipients
  • LE 540
  • Micelles
  • Retinoids
  • Tetrahydronaphthalenes
  • poly(ethylene oxide)-block-poly(beta-benzyl aspartate)
  • tamibarotene
  • Aspartic Acid
  • Polyethylene Glycols