Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells

Avudaiappan Maran, Mahrokh Dadsetan, Colleen M. Buenz, Kristen L. Shogren, Lichun Lu, Michael J Yaszemski

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2491-2499, 2013.

Original languageEnglish (US)
Pages (from-to)2491-2499
Number of pages9
JournalJournal of Biomedical Materials Research - Part A
Volume101 A
Issue number9
DOIs
StatePublished - Sep 2013

Fingerprint

Hydrogel
Hydrogels
Tumors
Acids
Composite materials
Polymers
Kinetics
Osteoblasts
Cell proliferation
Metabolites
Microspheres
Polyethylene glycols
Bone
Cells
Milk
2-methoxyestradiol
polylactic acid-polyglycolic acid copolymer
Fumarates
Chemical analysis
Estrogens

Keywords

  • 2-methoxyestradiol
  • hydrogel
  • oligo(polyethylene glycol) fumarate
  • osteosarcoma
  • poly (lactic-co-glycolic acid)

ASJC Scopus subject areas

  • Biomedical Engineering
  • Biomaterials
  • Ceramics and Composites
  • Metals and Alloys

Cite this

Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells. / Maran, Avudaiappan; Dadsetan, Mahrokh; Buenz, Colleen M.; Shogren, Kristen L.; Lu, Lichun; Yaszemski, Michael J.

In: Journal of Biomedical Materials Research - Part A, Vol. 101 A, No. 9, 09.2013, p. 2491-2499.

Research output: Contribution to journalArticle

Maran, Avudaiappan ; Dadsetan, Mahrokh ; Buenz, Colleen M. ; Shogren, Kristen L. ; Lu, Lichun ; Yaszemski, Michael J. / Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells. In: Journal of Biomedical Materials Research - Part A. 2013 ; Vol. 101 A, No. 9. pp. 2491-2499.
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AB - Osteosarcoma is a bone tumor that affects children and young adults. 2-Methoxyestradiol (2-ME), a naturally occurring estrogen metabolite, kills osteosarcoma cells, but does not affect normal osteoblasts. In order to effectively target osteosarcoma and improve the therapeutic index of the drug 2-ME, we have encapsulated 2-ME in a composite of oligo-(polyethylene glycol) fumarate (OPF) hydrogel and poly (lactic-co-glycolic acid) (PLGA) microspheres and investigated the effect of polymer composition on 2-ME release kinetics and osteosarcoma cell survival. The in vitro study shows that 2-ME can be released in a controlled manner over 21-days. The initial burst releases observed on day 1 were 50% and 32% for OPF and OPF/PLGA composites, respectively. The extended release kinetics show that 100% of the encapsulated 2-ME is released by day 12 from OPF, whereas the OPF/PLGA composites showed a release of 85% on day 21. 2-ME released from the polymers was biologically active and blocked osteosarcoma cell proliferation in vitro. Also, comparison of 2-ME delivery in osteosarcoma cells in culture, shows that direct treatment has no effect after 3 days, whereas polymer-mediated delivery produces anti-tumor effects that could be sustained for 21 days. These findings show that the OPF and PLGA polymeric system may prove to be useful in controlled and sustained delivery of 2-ME and could be further explored in the treatment of osteosarcoma. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 101A: 2491-2499, 2013.

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