Water-soluble HPMA copolymer - Prostaglandin E1 conjugates containing a cathepsin K sensitive spacer

Huaizhong Pan, Pavla Kopečková, Dong Wang, Jiyuan Yang, Scott Miller, Jindřich Kopeček

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

A novel bone targeting, N -(2-hydroxypropyl)methacrylamide (HPMA) copolymer based, prostaglandin E1 (PGE1) delivery system was designed, synthesized and characterized. PGE1 was bound to the polymer backbone via a spacer, composed of a cathepsin K sensitive tetrapeptide (Gly-Gly-Pro-Nle) and a self-eliminating 4-aminobenzyl alcohol structure. The HPMA copolymer conjugates were prepared by photo-initiated free radical copolymerization of HPMA, PGE1-containing macromonomer, and optionally a comonomer containing a reactive p -nitrophenyl ester group. The latter group was used as attachment points for the d-aspartic acid octapeptide targeting moieties. Incubation of the PGE1-containing macromonomer and HPMA copolymer-PGE1 conjugates with cathepsin K resulted in release of unmodified PGE1. The rate of release depended on the composition of the conjugate. The higher the PGE1 content in the conjugate, the slower the PGE1 release. This appeared to be the result of association of hydrophobic side-chains in aqueous media, which rendered the formation of the enzyme substrate complex more difficult. The data seems to indicate that HPMA copolymer-PGE1 conjugates have a potential in the treatment of osteoporosis and other bone diseases.

Original languageEnglish (US)
Pages (from-to)425-435
Number of pages11
JournalJournal of Drug Targeting
Volume14
Issue number6
DOIs
StatePublished - Jul 1 2006

Fingerprint

Cathepsin K
Alprostadil
Water
glycyl-glycyl-proline
N-(2-hydroxypropyl)methacrylamide
Bone Diseases
Aspartic Acid
Osteoporosis
Free Radicals
Polymers
Esters
Bone and Bones

Keywords

  • Cathepsin K sensitive spacer
  • HPMA
  • Osteoporosis
  • PGE
  • Polymer - Prostaglandin conjugates

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Water-soluble HPMA copolymer - Prostaglandin E1 conjugates containing a cathepsin K sensitive spacer. / Pan, Huaizhong; Kopečková, Pavla; Wang, Dong; Yang, Jiyuan; Miller, Scott; Kopeček, Jindřich.

In: Journal of Drug Targeting, Vol. 14, No. 6, 01.07.2006, p. 425-435.

Research output: Contribution to journalArticle

Pan, Huaizhong ; Kopečková, Pavla ; Wang, Dong ; Yang, Jiyuan ; Miller, Scott ; Kopeček, Jindřich. / Water-soluble HPMA copolymer - Prostaglandin E1 conjugates containing a cathepsin K sensitive spacer. In: Journal of Drug Targeting. 2006 ; Vol. 14, No. 6. pp. 425-435.
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