Toroidal-spiral particles for codelivery of anti-VEGFR-2 antibody and irinotecan: a potential implant to hinder recurrence of glioblastoma multiforme.
Heterogeneous toroidal-spiral particles (TSPs) were generated by polymer droplet sedimentation, interaction, and cross-linking. TSPs provide a platform for encapsulation and release of multiple compounds of different sizes and physicochemical properties. As a model system, we demonstrate the encapsulation and independently controlled release of an anti-VEGFR-2 antibody and irinotecan for the treatment of glioblastoma multiforme. The anti-VEGFR-2 antibody was released from the TS channels and its binding to HUVECs was confirmed by confocal microscopy and flow cytometry, suggesting active antibody encapsulation and release. Irinotecan, a small molecule drug, was released from the dense polymer matrix of poly(ethylene glycol) diacrylate (MW ~ 700 g/mol; PEGDA 700). Released irinotecan inhibited the proliferation of U251 malignant glioma cells. Since the therapeutic compounds are released through different pathways, specifically diffusion through the polymer matrix versus TS channels, the release rate can be controlled independently through the design of the structure and material of particle components.
Department of Chemical Engineering and §Department of Bioengineering, University of Illinois at Chicago , Chicago, Illinois 60607, United States.
Vishal
V
Sharma
Melanie
M
Köllmer
Magdalena
M
Szymusiak
Ludwig C
LC
Nitsche
Richard A
RA
Gemeinhart
Ying
Y
Liu
D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage* / Q000737:chemistry; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D016503:Drug Delivery Systems; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000276:immunology; D006801:Humans; D000077146:Irinotecan; D010316:Particle Size; D011108:Polymers / Q000737:chemistry; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000008:administration & dosage / Q000276:immunology*
D000888:Antibodies, Anti-Idiotypic; D011108:Polymers; D000077146:Irinotecan; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2; D002166:Camptothecin