Biodegradable polymeric system for cisplatin delivery: Development, in vitro characterization and investigation of toxicity profile

• Published in: Materials Science & Engineering C Vol. 38; pp. 85 - 93
• Main Authors: Alam, Noor, Khare, Vaibhav, Dubey, Ravindra, Saneja, Ankit, Kushwaha, Manoj, Singh, Gurdarshan, Sharma, Neelam, Chandan, Balkrishan, Gupta, Prem N.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2014
• Subjects: Animals; Biocompatible Materials - chemistry; Biodistribution; Blood Urea Nitrogen; Body Weight - drug effects; Calorimetry, Differential Scanning; Cell Death - drug effects; Cell Line, Tumor; Cisplatin; Cisplatin - pharmacology; Cisplatin - toxicity; Creatinine - blood; Drug Delivery Systems; Female; Humans; Lactic Acid - chemistry; Mass Spectrometry; Mice; Mice, Inbred BALB C; Nanoparticle; Nanoparticles - chemistry; Nanoparticles - ultrastructure; Nephrotoxicity; Particle Size; Poly (d,l-lactic co-glycolic) acid; Polyglycolic Acid - chemistry; Spectroscopy, Fourier Transform Infrared; Static Electricity; Tissue Distribution - drug effects; Toxicity Tests; Nanoparticle; Nephrotoxicity; Biodistribution; Cisplatin; Poly (d,l-lactic co-glycolic) acid
• ISSN: 0928-4931; 1873-0191
• DOI: 10.1016/j.msec.2014.01.043

Cisplatin is one of the most potent anticancer agent used in the treatment of various solid tumors, however, its clinical use is limited due to severe adverse effects including nephrotoxicity. In this investigation cisplatin loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles were developed and characterized for various in vitro characteristics including size distribution, zeta potential, drug loading and release profile. PLGA nanoparticles were successfully developed as investigated using scanning electron microscopy and exhibited average particles size and zeta potential as 284.8nm and −15.8mV, respectively. Fourier transform infrared spectroscopy and differential scanning calorimetry indicated an absence of any polymer–drug interactions. Cisplatin nanoparticles exhibited in vitro anticancer activity against A549 cells comparable to that of cisplatin solution. The biodistribution study in mice indicated that the kidney cisplatin level was significantly (p<0.01) lower with cisplatin nanoparticles than cisplatin solution. Following two cycles of cisplatin treatment, a week apart, blood urea nitrogen level was found to be higher in case of cisplatin solution as compared to cisplatin nanoparticles. Further, there was a significant (p<0.01) increase in plasma creatinine level in case of cisplatin solution as compared to cisplatin nanoparticles. Histopathological examination of kidney from cisplatin nanoparticles treated group revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of cisplatin solution. The results suggest that PLGA nanoparticle based formulation could be a potential option for cisplatin delivery. [Display omitted] •Cisplatin is detected by LCMS following complexation with DDTC.•Nanoparticles showed lower cisplatin accumulation in the kidney.•Nephrotoxicity was evaluated by BUN and creatinine level and by histopathology.•Nanoparticles exhibited lower nephrotoxicity.