Optimization of the hydrophobic domain in poly(ethylene oxide)-poly(varepsilon-caprolactone) based nano-carriers for the solubilization and delivery of Amphotericin B.

Abstract

The aim of the study was to develop a polymeric nano-carrier based on methoxy poly(ethylene oxide)-b-poly(epsilon-caprolactone) (MePEO-b-PCL) for the optimum solubilization and delivery of Amphotericin B (AmB). For this purpose, MePEO-b-PCL block co-polymers containing palmitoyl substituent on PCL (at a 100% substitution level) were synthesized through preparation of substituted monomer, that is, alpha-palmitoyl-epsilon-caprolactone, and further ring opening polymerization of this monomer by methoxy PEO (5000 g mol(-1)) using stannous octoate as catalyst. Prepared block co-polymers were characterized for their molecular weight by (1)H NMR and gel permeation chromatography, and assembled to polymeric nano-carriers. The self-assembly of synthesized MePEO-b-PPaCL to spherical particles of nanometer size range was shown by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The efficacy of nano-carriers formed from this structure (abbreviated as MePEO-b-PPaCL) in comparison to unmodified MePEO-b-PCL and those with benzyl and cholesteryl substituent on PCL (abbreviated as MePEO-b-PBCL and MePEO-b-PChCL, respectively) on the solubilization and hemolytic activity of AmB against rat red blood cells was assessed. Under identical conditions, the maximum solubilization of AmB was achieved by nano-carriers prepared from MePEO-b-PPaCL (436 microg/mL), followed by MePEO-b-PChCL (355 microg/mL), MePEO-b-PBCL (296 microg/mL) and MePEO-b-PCL (222 microg/mL). The hemolytic activity of AmB was reduced the most by its encapsulation in MePEO-b-PChCL nano-particles which showed only 7% hemolysis at 30 microg/mL AmB concentration. This was followed by MePEO-b-PCL nano-particles which illustrated 15% hemolysis, MePEO-b-PPaCL with 40% hemolysis and MePEO-b-PBCL with 60% hemolysis at 30 microg/mL AmB concentrations, respectively. In contrast Fungizone showed 90% hemolysis at 30 microg/mL AmB concentration. Based on the improved solubility and reduced hemolytic activity, the MePEO-b-PChCL nano-carriers are considered as optimum structures for AmB delivery.

• Authors: Arash Falamarzian, Afsaneh Lavasanifar
• Journal: Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 81 Issue 1 Pg. 313-20 (Nov 01 2010) ISSN: 1873-4367 [Electronic] Netherlands
• PMID: 20674292 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• Capsules
• Drug Carriers
• Lactones
• poly(ethylene oxide)-b-poly(caprolactone)
• Polyethylene Glycols
• Amphotericin B

Topics

• Amphotericin B (administration & dosage, chemistry, pharmacology)
• Animals
• Capsules
• Dose-Response Relationship, Drug
• Drug Carriers (chemistry)
• Drug Delivery Systems
• Hemolysis (drug effects)
• Hydrophobic and Hydrophilic Interactions
• Lactones (chemical synthesis, chemistry)
• Microscopy, Electron, Transmission
• Models, Chemical
• Molecular Structure
• Nanoparticles (chemistry, ultrastructure)
• Polyethylene Glycols (chemical synthesis, chemistry)
• Rats
• Rats, Sprague-Dawley
• Solubility