Novel local drug delivery system using thermoreversible gel in combination with polymeric microspheres or liposomes.
BACKGROUND
The purpose of our study was to evaluate the application of thermoreversible gelation polymer (TGP) as a local drug delivery system for malignant glioma.


METHODS
Polymeric microspheres or liposomes loaded with doxorubicin (sphere-dox or lipo-dox) were combined with TGP to provide continuous drug delivery of doxorubicin (dox) for kinetic release studies and cell viability assays on glioma cell lines in vitro. For in vivo studies, TGP loaded with dox alone (TGP-dox) was combined with sphere-dox or lipo-dox. Their antitumor effects on subcutaneous human glioma xenografts were evaluated in nude mice.


RESULTS
In vitro, TGP combined with sphere-dox or lipo-dox released dox for up to 30 days. In vivo, TGP-dox combined with sphere-dox or lipo-dox inhibited subcutaneous glioma tumor growth until day 32 and day 38, respectively.


CONCLUSIONS
TGP in combination with microspheres or liposomes successfully prolonged the release of dox and its antitumor effects.
Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Takao
T
Arai
Ofra
O
Benny
Tatsuhiro
T
Joki
Lata G
LG
Menon
Marcelle
M
Machluf
Toshiaki
T
Abe
Rona S
RS
Carroll
Peter M
PM
Black
D000178:Acrylamides / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004355:Drug Stability; D005909:Glioblastoma / Q000188:drug therapy*; D006358:Hot Temperature; D006801:Humans; D007150:Immunohistochemistry; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008297:Male; D008689:Methacrylates / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D008863:Microspheres; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D023041:Xenograft Model Antitumor Assays
D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D008689:Methacrylates; D011108:Polymers; D011092:Polyethylene Glycols; D004317:Doxorubicin