Effective antiproliferative effect of meloxicam on prostate cancer cells: development of a new controlled release system.
Recent studies have shown that COX-2 inhibitors, such as meloxicam, have demonstrated promising results when used with chemotherapy. Based on these findings, this is the first study in which the antiproliferative effect of meloxicam is investigated on two prostate cancer cell lines (PC3 and DU-145). We have also evaluated if this antiproliferative effect is dose- and/or time-dependent. Meloxicam is assayed at a concentration range of 10-800 microM for 24, 48 and 72 h. Our results reveal that meloxicam has a selective dose- and time-dependent antiproliferative effect against PC3 but not against DU-145 cells. In PC3 cells the IC(50) decreased from 740 microM at 24 h to 515 microM at 72 h after meloxicam treatment. Chemoembolization based on microspheres has been emerged as a novel and promising way for antitumoural therapy; therefore, in our study we have developed and characterized a new controlled release system consisting of biodegradable PLGA/PEG-derivative meloxicam microspheres. The optimized formulation has a mean particle size of 13.06+/-0.09 microm, mean encapsulation efficiency of 58.44+/-4.53% and releases 0.45+/-0.05 microg meloxicam/day/mg microspheres between days 3 and 28 of the in vitro release assay. In conclusion, we should consider meloxicam as a possible adjuvant agent in the treatment of prostate cancer.
Montejo
C
C
Departamento de Ciencias Farmacéuticas y de la Alimentación, Area de Farmacia y Tecnología Farmacéutica, Facultad de Farmacia, Ctra. Boadilla del Monte Km 5,300, Universidad CEU San Pablo, 28668 Madrid, Spain. debyrp@usp.b
Barcia
E
E
Negro
S
S
Fernández-Carballido
A
A
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020128:Inhibitory Concentration 50; D019344:Lactic Acid / Q000737:chemistry; D008297:Male; D000077239:Meloxicam; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013843:Thiazines / Q000008:administration & dosage / Q000494:pharmacology*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D003692:Delayed-Action Preparations; D013843:Thiazines; D013844:Thiazoles; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; D000077239:Meloxicam