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  3. Bioflavonoid hesperetin overcome bicalutamide induced toxicity by co-delivery in novel SNEDDS formulations: Optimization, in vivo evaluation and uptake mechanism

Bioflavonoid hesperetin overcome bicalutamide induced toxicity by co-delivery in novel SNEDDS formulations: Optimization, in vivo evaluation and uptake mechanism

  • Mater Sci Eng C Mater Biol Appl. 2017 Feb 1;71:954-964. doi: 10.1016/j.msec.2016.11.006.
Abhishek Arya 1,  Hafsa Ahmad 2,  Sachin Tulsankar 3,  Satish Agrawal 4,  Naresh Mittapelly 4,  Rajkumar Boda 2,  Rabi S Bhatta 5,  Kalyan Mitra 6,  Anil K Dwivedi 7
Affiliations

Affiliations

  • 1 Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226021, India; Academy of Scientific & Innovative Research, Chennai 600113, India. Electronic address: abhishekarya55@gmail.com.
  • 2 Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226021, India.
  • 3 Academy of Scientific & Innovative Research, Chennai 600113, India; Pharmacokinetics and Metabolism, CSIR-Central Drug Research Institute, Lucknow 226031, India.
  • 4 Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226021, India; Academy of Scientific & Innovative Research, Chennai 600113, India.
  • 5 Pharmacokinetics and Metabolism, CSIR-Central Drug Research Institute, Lucknow 226031, India.
  • 6 Electron Microscopy Unit, Sophisticated Analytical Equipment Facility, CSIR-Central Drug Research Institute, Lucknow, India.
  • 7 Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow 226021, India. Electronic address: anilcdri@gmail.com.
PMID: 27987794 DOI: 10.1016/j.msec.2016.11.006
Abstract

In the present study, we designed Bicalutamide (BCT) and Hesperetin (HSP) co-loaded self nano-emulsifying Drug Delivery system (SNEDDS) to encounter the problem of BCT induced toxicity, low solubility, and bioavailability. Optimized BCT-HSP SNEDDS would produce an emulsion of globule size 30.84±1.24nm with a high encapsulation efficiency of BCT (91.29%) and HSP (88.19%), and showed rapid drug release. DPPH assay confirmed the retention of antioxidant potential of HSP in SNEDDS. DCFH-DA confirmed intense green fluorescence in HSP treated groups due to the generation of Reactive Oxygen Species. Thermogravimetric analysis showed the change in the polymorphic form of BCT. After 14days of sub-acute toxicity study, no significant increase (p>0.05) in the hepatotoxicity markers was observed but BCT-HSP SNEDDS significantly decreased (p<0.001) the levels of nephrotoxicity biochemical markers. Additionally, the histopathological study showed that pulmonary fibrosis and alteration in the bowman's by BCT treatment were conquered by co-administration of HSP. BCT-HSP SNEDDS revealed high AUC0-t of BCT (1.23 fold) and HSP (3.42 fold) than aqueous suspension in male Sprague-Dawley rats. The BCT-HSP SNEDDS were absorbed by clathrin-mediated endocytosis and lymphatic transport absorption pathway. Our results proposed that the co-delivery approach may be useful for in vivo management of prostate Cancer.

Keywords

Antioxidant; Bicalutamide; Hesperetin; Prostate cancer; Reactive oxygen species; Toxicity.

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