title: 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: Department of Medical System Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea.
authors: Sun-Mi
authors: SM
authors: Lee
authors: New Drug Development Center (NDDC), Daegu-Gyeongbuk Medical Innovation Foundation (DGMIF), 80 Cheombok-ro, Dong-gu, Daegu 701-310, Republic of Korea.
authors: Joong-Heui
authors: JH
authors: Cho
authors: School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro (Oryong-dong), Buk-gu, Gwangju 500-712, Republic of Korea.
authors: So-Deok
authors: SD
authors: Lee
authors: Department of Medical System Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 500-712, Republic of Korea; School of Life Sciences, Gwangju Institute of Science and Technology (GIST), 123 Cheomdan-gwagiro (Oryong-dong), Buk-gu, Gwangju 500-712, Republic of Korea. Electronic address: yongchul@gist.ac.kr.
authors: Yong-Chul
authors: YC
authors: Kim
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007249:Inflammation / Q000188:drug therapy; D008689:Methacrylates / Q000008:administration & dosage* / Q000737:chemistry*; D015394:Molecular Structure; D053758:Nanoparticles / Q000737:chemistry*; D011714:Pyrans / Q000008:administration & dosage* / Q000737:chemistry*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008689:Methacrylates; C546468:P2RX7 protein, human; D011714:Pyrans; D058486:Receptors, Purinergic P2X7; C515107:poly(tetrahydropyranyl-2-methyl methacrylate)
keywords: Encapsulation; Nanoparticles; P2X(7) receptor antagonists; Poly(tetrahydropyran-2-yl methacrylate)(poly(THPMA)); pH sensitive polymer