Noor Alam1, Ravindra Dhar Dubey1, Ashok Kumar2, Mytre Koul2, Neelam Sharma2, Parduman Raj Sharma2, Bal Krishan Chandan2, Shashank K Singh2, Gurdarshan Singh3, Prem N Gupta4. 1. Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. 2. Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. 3. Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; PK-PD-Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. 4. Formulation & Drug Delivery Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India; PK-PD-Toxicology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India. Electronic address: pngupta10@gmail.com.
Abstract
AIMS: Cisplatin is one of the most potent chemotherapeutic agents acting against a variety of tumors, however, its use is mainly limited due to the dose limiting toxicities and acquired resistance to cisplatin. Folate functionalized albumin nanoparticles were developed for targeted delivery of drug to limit the adverse effects of cisplatin. MAIN METHODS: Cisplatin loaded nanoparticles functionalized with folate (CP-FA-BSA-NPs) were developed and characterized for various parameters. In order to investigate the targeting ability of folate conjugated nanoparticles, in vitro cellular uptake study was performed in folate receptor over expressing cells (MCF-7). Further, blood urea nitrogen (BUN) level, plasma creatinine level, body weight and kidney weight of the mice were measured followed by histopathological examination of various tissues to have an insight into the potential of developed formulation in the reduction of drug associated adverse effects. KEY FINDINGS: The cellular uptake studies demonstrated higher internalization of folate conjugated nanoparticles as compared to plain counterpart (CP-BSA-NPs). Following two cycles of cisplatin treatment, a week apart, BUN and plasma creatinine level were found to be significantly higher in case of free cisplatin as compared to saline, CP-BSA-NPs and CP-FA-BSA-NPs treated groups. Body weight and kidney weight of free cisplatin treated mice were significantly reduced as compared to other group. Histopathological examination of kidney from CP-BSA-NPs and CP-FA-BSA-NPs treated groups revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of free cisplatin. SIGNIFICANCE: The results demonstrated the potential of developed formulation in reducing the adverse effects of cisplatin.
AIMS: Cisplatin is one of the most potent chemotherapeutic agents acting against a variety of tumors, however, its use is mainly limited due to the dose limiting toxicities and acquired resistance to cisplatin. Folate functionalized albumin nanoparticles were developed for targeted delivery of drug to limit the adverse effects of cisplatin. MAIN METHODS:Cisplatin loaded nanoparticles functionalized with folate (CP-FA-BSA-NPs) were developed and characterized for various parameters. In order to investigate the targeting ability of folate conjugated nanoparticles, in vitro cellular uptake study was performed in folate receptor over expressing cells (MCF-7). Further, blood ureanitrogen (BUN) level, plasma creatinine level, body weight and kidney weight of the mice were measured followed by histopathological examination of various tissues to have an insight into the potential of developed formulation in the reduction of drug associated adverse effects. KEY FINDINGS: The cellular uptake studies demonstrated higher internalization of folate conjugated nanoparticles as compared to plain counterpart (CP-BSA-NPs). Following two cycles of cisplatin treatment, a week apart, BUN and plasma creatinine level were found to be significantly higher in case of free cisplatin as compared to saline, CP-BSA-NPs and CP-FA-BSA-NPs treated groups. Body weight and kidney weight of free cisplatin treated mice were significantly reduced as compared to other group. Histopathological examination of kidney from CP-BSA-NPs and CP-FA-BSA-NPs treated groups revealed no kidney damage, however, a sign of nephrotoxicity was observed in the case of free cisplatin. SIGNIFICANCE: The results demonstrated the potential of developed formulation in reducing the adverse effects of cisplatin.