Hydrogel-PLGA delivery system prolongs 2-methoxyestradiol-mediated anti-tumor effects in osteosarcoma cells.
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.
Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN, USA. maran.avudai@mayo.edu
Avudaiappan
A
Maran
Mahrokh
M
Dadsetan
Colleen M
CM
Buenz
Kristen L
KL
Shogren
Lichun
L
Lu
Michael J
MJ
Yaszemski
D000077584:2-Methoxyestradiol; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D001672:Biocompatible Materials; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D004958:Estradiol / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006801:Humans; D020100:Hydrogels; D019344:Lactic Acid; D008422:Materials Testing; D008863:Microspheres; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D011091:Polyesters; D011092:Polyethylene Glycols; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D018931:Antineoplastic Agents, Hormonal; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D020100:Hydrogels; D011091:Polyesters; C469550:oligo(poly(ethylene glycol)fumarate); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D004958:Estradiol; D000077584:2-Methoxyestradiol
2-methoxyestradiol; hydrogel; oligo(polyethylene glycol) fumarate; osteosarcoma; poly (lactic-co-glycolic acid)