Biomaterials 2013-09-01

Efficiency of high molecular weight backbone degradable HPMA copolymer-prostaglandin E1 conjugate in promotion of bone formation in ovariectomized rats.

Huaizhong Pan, Monika Sima, Scott C Miller, Pavla Kopečková, Jiyuan Yang, Jindřich Kopeček

Index: Biomaterials 34(27) , 6528-38, (2013)

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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.Copyright © 2013 Elsevier Ltd. All rights reserved.