title: New celecoxib multiparticulate systems to improve glioblastoma treatment.
abstract: Treatment of malignant gliomas consists of resection followed by radiotherapy and chemotherapy. Celecoxib (CXB), a selective COX-2 inhibitor, is able to control inflammation and pain, to improve the efficacy of radiotherapy, and to inhibit at high doses the growth of cancer cells. Two new delivery systems for CXB are developed: microspheres (MPs) for implantation in the brain after partial/complete removal of the tumor, and nanoparticles (NPs) for their potential to cross the blood brain barrier and deliver CXB into the CNS. Cell culture assays performed in PC12, SKN-AS and U373-MG cells demonstrate the antiproliferative affects of CXB, with EC50 values of 99.81 μM and 82.4 μM in U373-MG and SKN-AS cells. Encapsulation efficacy of CXB in formulation MP2 (20% CXB) was 74.6 ± 2.2% with a zero-order release rate of 47.8 μg/day/20mg microspheres for 34 days. Uncoated and polysorbate 80-coated CXB-NPs are prepared by nanoprecipitation. Mean sizes of uncoated and coated CXB-NPs were 173.6 ± 44.9 nm and 100.6 ± 62.1 nm. Cerebral cortex images showed a marked increase of fluorescence when the surfactant-coated NPs were administered to rats. These results suggest that both CXB formulations (MPs and NPs) are adequate systems to enhance the effects of chemotherapy in the treatment of malignant brain tumor.
authors: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors: M
authors: M
authors: Vera
authors: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors: E
authors: E
authors: Barcia
authors: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors: S
authors: S
authors: Negro
authors: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors: P
authors: P
authors: Marcianes
authors: Cartografia cerebral, Instituto Pluricisciplinar, Universidad Complutense de Madrid, Madrid, Spain.
authors: L
authors: L
authors: García-García
authors: Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain.
authors: K
authors: K
authors: Slowing
authors: Departamento de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Universidad Complutense de Madrid, Madrid, Spain. Electronic address: afernand@ucm.es.
authors: A
authors: A
authors: Fernández-Carballido
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000188:drug therapy*; D000068579:Celecoxib; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D008863:Microspheres; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011136:Polysorbates / Q000737:chemistry; D011720:Pyrazoles / Q000008:administration & dosage / Q000737:chemistry; D017208:Rats, Wistar; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D003692:Delayed-Action Preparations; D011136:Polysorbates; D011720:Pyrazoles; D013449:Sulfonamides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000068579:Celecoxib
keywords: Celecoxib; Microspheres; Nanoparticles; Polysorbate 80