New celecoxib multiparticulate systems to improve glioblastoma treatment

• Published in: International journal of pharmaceutics Vol. 473; no. 1-2; pp. 518 - 527
• Main Authors: Vera, M., Barcia, E., Negro, S., Marcianes, P., García-García, L., Slowing, K., Fernández-Carballido, A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2014
• Subjects: Animals; Brain Neoplasms - drug therapy; Celecoxib; Cell Line, Tumor; Cell Proliferation - drug effects; Cyclooxygenase 2 Inhibitors - administration & dosage; Cyclooxygenase 2 Inhibitors - chemistry; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Glioblastoma - drug therapy; Humans; Inflammation - drug therapy; Lactic Acid - chemistry; Male; Microspheres; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Polyglycolic Acid - chemistry; Polysorbate 80; Polysorbates - chemistry; Pyrazoles - administration & dosage; Pyrazoles - chemistry; Rats, Wistar; Sulfonamides - administration & dosage; Sulfonamides - chemistry; Nanoparticles; Microspheres; Celecoxib; Polysorbate 80
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.07.028

[Display omitted] 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 99.81μM and 82.4μM 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 47.8μg/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±44.9nm and 100.6±62.1nm. 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.