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Triphenylphosphonium functionalized Ficus religiosa L. extract loaded nanoparticles improve the mitochondrial function in oxidative stress induced diabetes

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ABSTRACT

The present study was aimed to enhance the mitochondrial function in oxidative stress-induced diabetes. To achieve this, Ficus religiosa L. extract loaded solid lipid nanoparticles (ETNPs) were prepared and functionalized by using triphenylphosphonium. Developed nanoparticles demonstrated desired quality attributes with sustained release for up to 24 h and excellent storage stability for up to 180 days at 40 ± 2°C and 75 ± 5% relative humidity. In vitro cytotoxicity assessment showed no toxicity of ETNPs. Interestingly, oral administration of ETNPs to diabetic rats demonstrated improved mitochondrial function by normalizing the mitochondrial morphology, intracellular calcium ion concentration, complexes I, II, IV, and V activity, mitochondrial membrane potential, and antioxidant levels. Further, reduction in apoptotic markers viz. cytochrome-C, caspase-3, and caspase-9 was observed following the ETNP treatment. Moreover, significant reduction in blood glucose and glycosylated hemoglobin while significant improvement in plasma insulin was observed as compared to the diabetic group following the treatment with developed formulation. Furthermore, histopathology studies confirmed the safety of the developed formulation and thus, data in hand collectively suggest that proposed strategy can be effectively used to improve the mitochondrial function in oxidative stress-induced diabetes along with better control over blood glucose and glycosylated hemoglobin.

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ACKNOWLEDGEMENTS

The first author is grateful to the Indian Institute of Technology (Banaras Hindu University), Varanasi for providing financial support in the form Teaching Assistantship funded by the Ministry of Human Resource Development, Government of India. Dulla Naveen Kumar is thankful to SERB for providing financial assistance in terms of JRF in one of the SERB sponsored project (SRG/2019/000150). Authors extend their sincere thanks to Mr. Vinay K Ahire, Consortium for Scientific Research, Indore, Madhya Pradesh, India for carrying out SEM study. The authors are thankful to Prof. Mukesh Doble, IIT Madras, Chennai for cell line studies. The authors are thankful to Prof. Sanjeev Kumar Mahto, School of Biomedical Engineering, IIT (BHU), Varanasi for his kind assistance in fluorescence microscopic studies.

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  1. Sanjay Singh

    Present address: Babasaheb Bhimrao Ambedkar University, Lucknow, Uttar Pradesh, 226025, India

Authors and Affiliations

  1. Department of Pharmaceutical Engineering & Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi, Uttar Pradesh, 221005, India

    Priyanka Karunanidhi, Nitin Verma, Dulla Naveen Kumar, Ashish Kumar Agrawal & Sanjay Singh

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  1. Priyanka Karunanidhi
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Karunanidhi, P., Verma, N., Kumar, D.N. et al. Triphenylphosphonium functionalized Ficus religiosa L. extract loaded nanoparticles improve the mitochondrial function in oxidative stress induced diabetes. AAPS PharmSciTech 22, 158 (2021). https://doi.org/10.1208/s12249-021-02016-8

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