First report on the efficacy of l-alanine-based in situ-forming implants for the long-term parenteral delivery of drugs

J Control Release. 2005 Nov 28;108(2-3):433-41. doi: 10.1016/j.jconrel.2005.08.016. Epub 2005 Sep 21.

Abstract

The recent advent of biotechnologies has led to the development of labile macromolecular therapeutic agents that require complex formulations for their efficient administration. This work reports a novel concept for the systemic, sustained delivery of such agents. The proposed approach is based on the spontaneous self-assembly of low-molecular weight amphiphilic amino acid derivatives in a hydrophobic pharmaceutical vehicle. The injectable, in situ-forming organogels were obtained by mixing N-stearoyl l-alanine (m)ethyl esters with a vegetable oil and a biocompatible hydrophilic solvent. The gels' in vivo-delivering properties were evaluated in rats with leuprolide, a luteinizing hormone-releasing hormone agonist used in prostate cancer, endometriosis and precocious puberty treatment. Following subcutaneous injection, the gels degraded and gradually released leuprolide for 14 to 25 days. Drug release was accompanied by sustained castration lasting up to 50 days, as assessed by testosterone levels. This study demonstrates that in situ-forming implants based on l-alanine derivatives represent a novel injectable platform for the controlled delivery of hydrophilic compounds, which is simpler than currently available implant and microsphere technologies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / analogs & derivatives*
  • Alanine / chemistry*
  • Animals
  • Antineoplastic Agents, Hormonal / administration & dosage
  • Antineoplastic Agents, Hormonal / pharmacokinetics
  • Area Under Curve
  • Chromatography, High Pressure Liquid
  • Delayed-Action Preparations
  • Drug Delivery Systems*
  • Drug Implants*
  • Esters
  • Gels
  • Leuprolide / administration & dosage
  • Leuprolide / pharmacokinetics
  • Lipids / chemistry
  • Male
  • Microspheres
  • Pharmaceutical Vehicles
  • Plant Oils
  • Rats
  • Rats, Wistar
  • Solvents
  • Testosterone / blood

Substances

  • Antineoplastic Agents, Hormonal
  • Delayed-Action Preparations
  • Drug Implants
  • Esters
  • Gels
  • Lipids
  • Pharmaceutical Vehicles
  • Plant Oils
  • Solvents
  • Testosterone
  • Leuprolide
  • Alanine