Nanoparticle-encapsulated P2X₇ receptor antagonist in a pH-sensitive polymer as a potential local drug delivery system to acidic inflammatory environments.

Abstract

We have developed nanoparticles of anti-inflammatory P2X7 receptor antagonist encapsulated in a pH-sensitive polymer, poly(tetrahydropyran-2-yl methacrylate) (poly(THPMA)), as a potential local drug delivery system to target to acidic inflammatory environments, in which P2X7 receptors are implicated in the pathology of inflammation via the activation of immune cells. The nanoparticles were prepared using single emulsion methods, also their size and shape were confirmed by microscopy and spectroscopy, etc. The profiles of the pH-dependent degradation, release of antagonist and biological activities were investigated. The nanoparticles that encapsulated the 3,5-dichloropyridine derivative (2) with poly(THPMA), were observed to be more slowly cleaved than the blank nanoparticles. Moreover, the free P2X7 receptor antagonists potently inhibited the receptor activation, whereas the nanoparticles of the 3,5-dichloropyridine derivative (2) encapsulated poly(THPMA) exhibited much lower P2X7 antagonistic activity through sustained encapsulation. Thus, the nanoparticles of the 3,5-dichloropyridine derivative (2) encapsulated poly(THPMA) may be utilized to develop a pH-sensitive local drug delivery system for controlled release of anti-inflammatory therapeutics in acidic physiological environments.

• Authors: Sun-Mi Lee, Joong-Heui Cho, So-Deok Lee, Yong-Chul Kim
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 19 Pg. 4197-202 (Oct 01 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26303894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Methacrylates
• P2RX7 protein, human
• Pyrans
• Receptors, Purinergic P2X7
• poly(tetrahydropyranyl-2-methyl methacrylate)

Topics

• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, pharmacology, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Delivery Systems
• Humans
• Hydrogen-Ion Concentration
• Inflammation (drug therapy)
• Methacrylates (administration & dosage, chemistry)
• Molecular Structure
• Nanoparticles (chemistry)
• Pyrans (administration & dosage, chemistry)
• Receptors, Purinergic P2X7 (metabolism)
• Structure-Activity Relationship