Feasibility of using a bone-targeted, macromolecular delivery system coupled with prostaglandin E1 to promote bone formation in aged, estrogen-deficient rats

S. C. Miller, H. Pan, Dong Wang, B. M. Bowman, P. Kopečková, J. Kopeček

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Purpose. Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer-Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods. The uptake of FITC-labeled HPMA copolymer-Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results. P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE 1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions. HPMA copolymers can be targeted to bone surfaces using Asp 8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases.

Original languageEnglish (US)
Pages (from-to)2889-2895
Number of pages7
JournalPharmaceutical Research
Volume25
Issue number12
DOIs
StatePublished - Dec 1 2008

Fingerprint

hydroxypropyl methacrylate
Alprostadil
Osteogenesis
Fluorescein-5-isothiocyanate
Rats
Bone
Estrogens
Bone and Bones
Copolymers
Tetracycline
Injections
Cathepsin K
Therapeutic Uses
Prostaglandins E

Keywords

  • Bone formation
  • HPMA
  • Macromolecular therapeutics
  • Prostaglandin
  • Rats

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

Cite this

Feasibility of using a bone-targeted, macromolecular delivery system coupled with prostaglandin E1 to promote bone formation in aged, estrogen-deficient rats. / Miller, S. C.; Pan, H.; Wang, Dong; Bowman, B. M.; Kopečková, P.; Kopeček, J.

In: Pharmaceutical Research, Vol. 25, No. 12, 01.12.2008, p. 2889-2895.

Research output: Contribution to journalArticle

@article{eb0cbbab8be64f418caa046a0b21dd7b,
title = "Feasibility of using a bone-targeted, macromolecular delivery system coupled with prostaglandin E1 to promote bone formation in aged, estrogen-deficient rats",
abstract = "Purpose. Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer-Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods. The uptake of FITC-labeled HPMA copolymer-Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results. P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE 1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions. HPMA copolymers can be targeted to bone surfaces using Asp 8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases.",
keywords = "Bone formation, HPMA, Macromolecular therapeutics, Prostaglandin, Rats",
author = "Miller, {S. C.} and H. Pan and Dong Wang and Bowman, {B. M.} and P. Kopečkov{\'a} and J. Kopeček",
year = "2008",
month = "12",
day = "1",
doi = "10.1007/s11095-008-9706-0",
language = "English (US)",
volume = "25",
pages = "2889--2895",
journal = "Pharmaceutical Research",
issn = "0724-8741",
publisher = "Springer New York",
number = "12",

}

TY - JOUR

T1 - Feasibility of using a bone-targeted, macromolecular delivery system coupled with prostaglandin E1 to promote bone formation in aged, estrogen-deficient rats

AU - Miller, S. C.

AU - Pan, H.

AU - Wang, Dong

AU - Bowman, B. M.

AU - Kopečková, P.

AU - Kopeček, J.

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Purpose. Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer-Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods. The uptake of FITC-labeled HPMA copolymer-Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results. P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE 1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions. HPMA copolymers can be targeted to bone surfaces using Asp 8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases.

AB - Purpose. Macromolecular delivery systems have therapeutic uses because of their ability to deliver and release drugs to specific tissues. The uptake and localization of HPMA copolymers using Asp8 as the bone-targeting moiety was determined in aged, ovariectomized (ovx) rats. PGE1 was attached via a cathepsin K-sensitive linkage to HPMA copolymer-Asp8 conjugate and was tested to determine if it could promote bone formation. Materials and Methods. The uptake of FITC-labeled HPMA copolymer-Asp8 conjugate (P-Asp8-FITC) on bone surfaces was compared with the mineralization marker, tetracycline. Then a targeted PGE1-HPMA copolymer conjugate (P-Asp8-FITC-PGE1) was given as a single injection and its effects on bone formation were measured 4 weeks later. Results. P-Asp8-FITC preferentially deposited on resorption surfaces, unlike tetracycline. A single injection of P-Asp8-FITC-PGE 1 resulted in greater indices of bone formation in aged, ovx rats. Conclusions. HPMA copolymers can be targeted to bone surfaces using Asp 8, with preferential uptake on resorption surfaces. Additionally, PGE1 attached to the Asp8-targeted HPMA copolymers and given by a single injection resulted in greater bone formation measured 4 weeks later. This initial in vivo study suggests that macromolecular delivery systems targeted to bone may offer some therapeutic opportunities and advantages for the treatment of skeletal diseases.

KW - Bone formation

KW - HPMA

KW - Macromolecular therapeutics

KW - Prostaglandin

KW - Rats

UR - http://www.scopus.com/inward/record.url?scp=57149144795&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57149144795&partnerID=8YFLogxK

U2 - 10.1007/s11095-008-9706-0

DO - 10.1007/s11095-008-9706-0

M3 - Article

VL - 25

SP - 2889

EP - 2895

JO - Pharmaceutical Research

JF - Pharmaceutical Research

SN - 0724-8741

IS - 12

ER -