title: Efficiency of high molecular weight backbone degradable HPMA copolymer-prostaglandin E1 conjugate in promotion of bone formation in ovariectomized rats.
abstract: Multiblock, high molecular weight, linear, backbone degradable HPMA copolymer-prostaglandin E1 (PGE1) conjugate has been synthesized by RAFT polymerization mediated by a new bifunctional chain transfer agent (CTA), which contains an enzymatically degradable oligopeptide sequence flanked by two dithiobenzoate groups, followed by postpolymerization aminolysis and thiol-ene chain extension. The multiblock conjugate contains Asp8 as the bone targeting moiety and enzymatically degradable bonds in the polymer backbone; in vivo degradation produces cleavage products that are below the renal threshold. Using an ovariectomized (OVX) rat model, the accumulation in bone and efficacy to promote bone formation was evaluated; low molecular weight conjugates served as control. The results indicated a higher accumulation in bone, greater enhancement of bone density, and higher plasma osteocalcin levels for the backbone degradable conjugate.
authors.affiliation: Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Huaizhong
authors.initials: H
authors.lastname: Pan
authors.forename: Monika
authors.initials: M
authors.lastname: Sima
authors.forename: Scott C
authors.initials: SC
authors.lastname: Miller
authors.forename: Pavla
authors.initials: P
authors.lastname: Kopečková
authors.forename: Jiyuan
authors.initials: J
authors.lastname: Yang
authors.forename: Jindřich
authors.initials: J
authors.lastname: Kopeček
mesh_terms: D000527:Alprostadil / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D045930:Anabolic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D008689:Methacrylates / Q000737:chemistry / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D045930:Anabolic Agents; D004337:Drug Carriers; D008689:Methacrylates; D000527:Alprostadil; C032802:hydroxypropyl methacrylate