Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers

Dong Wang, Monika Sima, R Lee Mosley, Jasmine P. Davda, Nicole Tietze, Scott C. Miller, Peter R. Gwilt, Pavla Kopečková, Jindřich Kopeček

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Osteotropicity of novel bone-targeted HPMA copolymer conjugates has been demonstrated previously with bone histomorphometric analysis. The pharmacokinetics and biodistribution of this delivery system were investigated in the current study with healthy young BALB/c mice. The 125l-labeled bone-targeted and control (nontargeted) HPMA copolymers were administered intravenously to mice, and their distribution to different organs and tissues was followed using a γ counter and single photon emission computed tomography (SPECT). Both the invasive and noninvasive data further confirmed that the incorporation of D-aspartic acid octapeptide (D-Asp8) as bone-targeting moiety could favorably deposit the HPMA copolymers to the entire skeleton, especially to the high bone turnover sites. To evaluate the influence of molecular weight, three fractions (Mw of 24, 46, and 96 KDa) of HPMA copolymer-D-Asp8 conjugate were prepared and evaluated. Higher molecular weight of the conjugate enhanced the deposition to bone due to the prolonged half-life in circulation, but it weakened the bone selectivity. A higher content of bone-targeting moiety (D-Asp8) in the conjugate is desirable to achieve superior hard tissue selectivity. Further validation of the bone-targeting efficacy of the conjugates in animal models of osteoporosis and other skeletal diseases is needed in the future.

Original languageEnglish (US)
Pages (from-to)717-725
Number of pages9
JournalMolecular Pharmaceutics
Volume3
Issue number6
DOIs
StatePublished - Nov 1 2006

Fingerprint

hydroxypropyl methacrylate
Drug Delivery Systems
Pharmacokinetics
Bone and Bones
Molecular Weight
D-Aspartic Acid
N-(2-hydroxypropyl)methacrylamide
Bone Remodeling
Single-Photon Emission-Computed Tomography
Skeleton
Osteoporosis
Half-Life
Animal Models

Keywords

  • Biodistribution
  • Bone targeting
  • Drug delivery
  • HPMA copolymer
  • Pharmacokinetics
  • SPECT

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmaceutical Science
  • Drug Discovery

Cite this

Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers. / Wang, Dong; Sima, Monika; Mosley, R Lee; Davda, Jasmine P.; Tietze, Nicole; Miller, Scott C.; Gwilt, Peter R.; Kopečková, Pavla; Kopeček, Jindřich.

In: Molecular Pharmaceutics, Vol. 3, No. 6, 01.11.2006, p. 717-725.

Research output: Contribution to journalArticle

Wang, Dong ; Sima, Monika ; Mosley, R Lee ; Davda, Jasmine P. ; Tietze, Nicole ; Miller, Scott C. ; Gwilt, Peter R. ; Kopečková, Pavla ; Kopeček, Jindřich. / Pharmacokinetic and biodistribution studies of a bone-targeting drug delivery system based on N-(2-hydroxypropyl)methacrylamide copolymers. In: Molecular Pharmaceutics. 2006 ; Vol. 3, No. 6. pp. 717-725.
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