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Enhanced Drug Carriage Efficiency of Curcumin-Loaded PLGA Nanoparticles in Combating Diabetic Nephropathy via Mitigation of Renal Apoptosis

  • Asmita Samadder (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Banani Bhattacharjee (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Sudatta Dey (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Arnob Chakrovorty (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Rishita Dey (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Priyanka Sow (Cytogenetics and Molecular Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Debojyoti Tarafdar (Department of Chemistry, Chanchal College, Affiliated to The University of Gour Banga) ;
  • Maharaj Biswas (Endocrinology and Reproductive Biology Laboratory, Department of Zoology, University of Kalyani) ;
  • Sisir Nandi (Department of Pharmaceutical Chemistry, Global Institute of Pharmaceutical Education and Research, Veer Madho Singh Bhandari Uttarakhand Technical University)
  • 투고 : 2023.06.16
  • 심사 : 2023.12.18
  • 발행 : 2024.03.31

초록

Background: Diabetic nephropathy (DN) is one of the major complications of chronic hyperglycaemia affecting normal kidney functioning. The ayurvedic medicine curcumin (CUR) is pharmaceutically accepted for its vast biological effects. Objectives: The Curcuma-derived diferuloylmethane compound CUR, loaded on Poly (lactide-co-glycolic) acid (PLGA) nanoparticles was utilized to combat DN-induced renal apoptosis by selectively targeting and modulating Bcl2. Methods: Upon in silico molecular docking and screening study CUR was selected as the core phytocompound for nanoparticle formulation. PLGA-nano-encapsulated-curcumin (NCUR) were synthesized following standard solvent displacement method. The NCUR were characterized for shape, size and other physico-chemical properties by Atomic Force Microscopy (AFM), Dynamic Light Scattering (DLS) and Fourier-Transform Infrared (FTIR) Spectroscopy studies. For in vivo validation of nephro-protective effects, Mus musculus were pre-treated with CUR at a dose of 50 mg/kg b.w. and NCUR at a dose of 25 mg/kg b.w. (dose 1), 12.5 mg/kg b.w (dose 2) followed by alloxan administration (100 mg/kg b.w) and serum glucose levels, histopathology and immunofluorescence study were conducted. Results: The in silico study revealed a strong affinity of CUR towards Bcl2 (dock score -10.94 Kcal/mol). The synthesized NCUR were of even shape, devoid of cracks and holes with mean size of ~80 nm having -7.53 mV zeta potential. Dose 1 efficiently improved serum glucose levels, tissue-specific expression of Bcl2 and reduced glomerular space and glomerular sclerosis in comparison to hyperglycaemic group. Conclusion: This study essentially validates the potential of NCUR to inhibit DN by reducing blood glucose level and mitigating glomerular apoptosis by selectively promoting Bcl2 protein expression in kidney tissue.

키워드

과제정보

The authors acknowledge the Department of Zoology and S.N. Bose Innovation Centre, University of Kalyani and GIPER, Uttarakhand for providing the infrastructural and instrumentation support for this study. SD, PS and RD extend their thankfulness to UGC for the SRF-fellowship. AC is grateful to University of Kalyani for URS (University Research Scholar) fellowship. BB is grateful to Govt. of West Bengal for SVMCM fellowship.

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