Monoglyceride-based self-assembling copolymers as carriers for poorly water-soluble drugs

Int J Pharm. 2009 Dec 1;382(1-2):244-53. doi: 10.1016/j.ijpharm.2009.07.036. Epub 2009 Aug 8.

Abstract

To develop self-assembling polymers forming polymeric micelles and increasing the solubility of poorly soluble drugs, amphiphilic polymers containing a hydrophilic PEG moiety and a hydrophobic moiety derived from monoglycerides and polyethers were designed. The biodegradable copolymers were obtained via a polycondensation reaction of polyethylene glycol (PEG), monooleylglyceride (MOG) and succinic anhydride (SA). Polymers with molecular weight below 10,000 g/mol containing a minimum of 40 mol% PEG and a maximum of 10 mol% MOG self-assembled spontaneously in aqueous media upon gentle mixing. They formed particles with a diameter of 10 nm although some aggregation was evident. The critical micellar concentration varied between 3x10(-4) and 4x10(-3) g/ml, depending on the polymer. The cloud point (> or = 66 degrees C) and flocculation point (> or = 0.89 M) increased with the PEG chain length. At a 1% concentration, the polymers increased the solubility of poorly water-soluble drug candidates up to 500-fold. Drug solubility increased as a function of the polymer concentration. HPMC capsules filled with these polymers disintegrated and released model drugs rapidly. Polymer with long PEG chains had a lower cytotoxicity (MTT test) on Caco-2 cells. All of these data suggest that the object polymers, in particular PEG1000/MOG/SA (45/5/50) might be potential candidates for improving the oral biopharmaceutical performance of poorly soluble drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caco-2 Cells
  • Capsules
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Drug Carriers*
  • Drug Compounding
  • Flocculation
  • Humans
  • Hypromellose Derivatives
  • Inhibitory Concentration 50
  • Kinetics
  • Methylcellulose / analogs & derivatives
  • Methylcellulose / chemistry
  • Micelles
  • Molecular Weight
  • Monoglycerides / chemical synthesis*
  • Monoglycerides / toxicity
  • Particle Size
  • Pharmaceutical Preparations / chemistry*
  • Polyethylene Glycols / chemical synthesis*
  • Polyethylene Glycols / toxicity
  • Solubility
  • Solvents / chemistry*
  • Succinic Anhydrides / chemical synthesis*
  • Succinic Anhydrides / toxicity
  • Surface Properties
  • Technology, Pharmaceutical / methods
  • Water / chemistry*

Substances

  • Capsules
  • Drug Carriers
  • Micelles
  • Monoglycerides
  • Pharmaceutical Preparations
  • Solvents
  • Succinic Anhydrides
  • Water
  • Hypromellose Derivatives
  • Polyethylene Glycols
  • succinic anhydride
  • Methylcellulose