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Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats

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Abstract

The present investigation is focused on improving oral bioavailability of poorly soluble and lipophilic drugs, curcumin (CRM) and duloxetine (DXH), through the solid self-nanoemulsifying drug delivery system (S-SNEDDS) and identifying their potential against attenuation of NP in chronic constriction injury (CCI)–induced rats through the solid self-nanoemulsifying drug delivery system (S-SNEDDS). The optimized batch of S-SNEDDS reported was containing CRM and DXH (30 mg each), castor oil (20% w/w), tween-80 (40% w/w), transcutol-P (40% w/w), and syloid 244 FP (1 g). The high dose of each of naïve CRM (NCH), naïve DXH (NDH), physical mixture of DXH and CRM (C-NCM-DXH), S-SNEDDS-CRM (SCH), S-SNEDDS-DXH (SDH), and S-SNEDDS-CRM-DXH (C-SCH-SDH) was subjected for MTT assay. The developed formulations were subjected to pharmacokinetic studies and results showed about 8 to 11.06 and 2-fold improvement in oral bioavailability of CRM and DXH through S-SNEDDS. Furthermore, CCI-induced male Wistar rats were treated with SSNEDDS containing CRM and DXH, S-SNEDDS containing individual drug, individual naïve forms, and their combination from the day of surgery for 14 days and evaluated for behavioral at pre-determined time intervals. On the terminal day, animals were sacrificed to assess tissue myeloperoxidase, superoxide anion, protein, tumor necrosis factor-α, total calcium levels, and histopathological changes. Pronounced effect was observed in rats treated with S-SNEDDS containing both drugs with respect to rats receiving any of other treatments owing to enhanced oral bioavailability through S-SNEDDS. Therefore, it can be concluded that S-SNEDDS of both drugs and their coadministration can accelerate the prevention of NP.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, 144411, India

    Bimlesh Kumar, Sachin Kumar Singh, Monica Gulati, Varun Garg, Narendra Kumar Pandey, Saurabh Singh & Indu Melkani

  2. Department of Physiology and Pharmacology, Acharya and B.M. Reddy College of Pharmacy, Soladeuanahalli Hesargatta Road, Chikkabanawara Post, Bangalore, Karnataka, 560 090, India

    T. Prakash

  3. Department of Pharm. Sci. & Tech, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India

    Amit Bhatia

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  1. Bimlesh Kumar
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Correspondence to T. Prakash.

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Approval for this study was granted with protocol no: LPU/LSPS/IAEC/CPCSEA/MEETING NO.1/SEPTEMBER2015/2016 PROTOCOL NO.2. All parts of experiment were strictly carried out in accordance with the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA).

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Kumar, B., Singh, S.K., Prakash, T. et al. Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats. Neurol Sci 42, 1785–1797 (2021). https://doi.org/10.1007/s10072-020-04628-7

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