Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcu
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ORIGINAL ARTICLE
Pharmacokinetic and pharmacodynamic evaluation of Solid self-nanoemulsifying delivery system (SSNEDDS) loaded with curcumin and duloxetine in attenuation of neuropathic pain in rats Bimlesh Kumar 1 & Sachin Kumar Singh 1 & T. Prakash 2 & Amit Bhatia 3 & Monica Gulati 1 & Varun Garg 1 & Narendra Kumar Pandey 1 & Saurabh Singh 1 & Indu Melkani 1 Received: 17 December 2019 / Accepted: 23 July 2020 # Fondazione Società Italiana di Neurologia 2020
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 SSNEDDS-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 SSNEDDS. 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. Keywords Curcumin . Duloxetine . Chronic constriction injury . TNF-α . Calcium inhibition
Introduction
* T. Prakash [email protected] 1
School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab 144411, India
2
Department of Physiology and Pharmacology, Acharya and B.M. Reddy College of Pharmacy, Soladeuanahalli Hesargatta Road, Chikkabanawara Post, Bangalore, Karnataka 560 090, India
3
Department of Pharm. Sci. & Tech, Maharaja Ranjit Singh Punjab Technical University, Bathinda, Punjab, India
Abnormal sensory processing in peripheral as well as central nervous systems develops a chronic painful condition known as neuropathic pain (NP) which is characterized by allodynia and hyperalgesia [1]. Conventional therapies like non-steroidal anti-inflammatory drugs (NSAIDs), opioid analgesics, tricyclic antidepressants (
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