Pharmacodynamics of cisplatin-loaded PLGA nanoparticles administered to tumor-bearing mice.
Biodegradable poly (lactic-co-glycolic) acid (PLGA) nanoparticles incorporating cisplatin have been developed to evaluate its in vivo efficacy in tumor-bearing mice. In vitro study proved two mechanisms of action for cisplatin depending on the dose and the rate at which this dose is delivered. In vivo study, 5mg/kg of cisplatin nanoparticles administered to mice, exhibited a tumor inhibition similar to free cisplatin, although the area under cisplatin concentration-time curve between 0 and 21days (AUC(0-21)) had lower value for the formulation than for drug solution (P<0.05). This result was associated with a higher activation of apoptosis in tumor, mediated by caspase-3, after nanoparticles administration. Toxicity measured as the change in body weight, and blood urea nitrogen (BUN) plasma levels showed that cisplatin nanoparticles treatment did not induce significant changes in both parameters compared to control, while for free drug, a statistical (P<0.01) increase was observed. In addition, a good correlation was found between time profiles of tumor volume and vascular endothelial growth factor (VEGF) plasma levels, suggesting that its expression could help to follow the efficacy of the treatment. Therefore, the PLGA nanoparticles seem to provide a promising carrier for cisplatin administration avoiding its side effects without a reduction of the efficacy, which was consistent with a higher activation of apoptosis than free drug.
Moreno
Daniel
D
Department of Pharmacy and Pharmaceutical Technology, University of Navarra, Pamplona, Spain.
Zalba
Sara
S
Navarro
Iñigo
I
Tros de Ilarduya
Conchita
C
Garrido
María J
MJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects; D001806:Blood Urea Nitrogen; D001835:Body Weight / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D005260:Female; D019344:Lactic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004337:Drug Carriers; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D053148:Caspase 3; D002945:Cisplatin