The preparation and characterization of anti-VEGFR2 conjugated, paclitaxel-loaded PLLA or PLGA microspheres for the systemic targeting of human prostate tumors.
OBJECTIVE
The objective of this study was to manufacture paclitaxel (PTX) loaded polymeric microspheres, that were surface conjugated with antibodies to vascular endothelial growth factor receptor 2 (anti-VEGFR2), for systemic targeting to angiogenic sites in prostate tumors.


METHODS
Microspheres were manufactured in the 1-3 microm size range from poly (l-lactic acid) (PLLA) or poly (lactide-co-glycolide) (PLGA) by a modified solvent evaporation method using Polytron homogenization followed by high speed dispersion in poly vinyl alcohol. Antibodies were conjugated to the surface of these microspheres using cyanogen bromide activation of the polymer surface. Cell Binding was determined using human umbilical vein endothelial cells (HUVECs) in vitro. Efficacy determinations were made using human prostate tumors (PC-3) grown subcutaneously in mice.


RESULTS
Antibodies were effectively bound to the surface of PLLA and PLGA microspheres. Anti-VEGFR2 conjugated PLLA microspheres bound strongly to HUVEC's. Pilot efficacy studies in mice showed variability but demonstrated a significant inhibition of tumor growth following the systemic administration of a single dose of PTX-loaded anti-VEGFR2 conjugated PLLA microspheres as compared to non-antibody-conjugated PTX-loaded microspheres.


CONCLUSIONS
Anti-VEGFR2 conjugated PLLA microspheres containing PTX may offer an effective way of administering a controlled release formulation of the drug to target prostate tumors.
Lu
Jianjun
J
Division of Pharmaceutics and Biopharmaceutics, Faculty of Pharmaceutical Sciences, The University of British Columbia, 2146 East Mall, Vancouver, BC, Canada V6T 1Z3.
Jackson
John K
JK
Gleave
Martin E
ME
Burt
Helen M
HM
D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage / Q000627:therapeutic use*; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004339:Drug Compounding; D016503:Drug Delivery Systems; D042783:Endothelial Cells / Q000187:drug effects; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry; D019344:Lactic Acid; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D009368:Neoplasm Transplantation; D017239:Paclitaxel / Q000008:administration & dosage / Q000627:therapeutic use*; D010316:Particle Size; D010865:Pilot Projects; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000276:immunology*
D019138:Antibodies, Blocking; D000972:Antineoplastic Agents, Phytogenic; D007074:Immunoglobulin G; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D040301:Vascular Endothelial Growth Factor Receptor-2; D016650:Fluorescein-5-isothiocyanate; D017239:Paclitaxel