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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Remifentanil and Propofol Co-loaded Nanoemulsion: Formulation Development and In vivo Pharmacodynamic Evaluation

Author(s): Lei Hou and Hang Tian*

Volume 21, Issue 2, 2024

Published on: 20 October, 2022

Page: [320 - 328] Pages: 9

DOI: 10.2174/1570180819666220928150516

Price: $65

Abstract

Background: The present work is an effort to develop novel propofol (PPF) and remifentanil (RFT) co-loaded nanoemulsion (NME) for the treatment of anesthetic effects.

Methods: The PPF/RFT NME was prepared via the high-pressure homogenization method. Its physicochemical properties were assessed to ensure good quality and suitability for i.v. administration. We also studied the in vivo pharmacokinetics and pharmacodynamics of PPF/RFT NME in dogs with an optimized formulation.

Results: This study showed that the mean particle size of PPF/RFT NME was 124.2 nm and the zeta potential was −20.6 mV. In the stability test, the NME maintained a good round shape and did not demonstrate any significant changes in physicochemical characteristics. In terms of the in vitro release, the early burst release of the NME preparations containing PPF or RFT was ideal in clinical practice, where a loading dose or a rapid onset of the drug was required. Based on histopathological observations, no histological change occurred to the rat organs after the administration of PPF/RFT NME. Regarding pharmacodynamics, compared with the combination group at the same dose, PPF/RFT NME could make animals enter the anesthetic state faster and the anesthetic effects last longer. In addition, vital signs of PPF/RFT NME could be maintained in a good state while better effects were delivered.

Conclusion: This study used PPF and RFT to prepare a compound NME. This could reduce the anesthesiologist's administration time and make the anesthesia process more efficient.

Keywords: Remifentanil, Propofol, nanoemulsion, anesthetic effects, pharmacodynamic, anesthesia

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[1]
Zhou, C.; Liu, J.; Chen, X.D. General anesthesia mediated by effects on ion channels. World J. Crit. Care Med., 2012, 1(3), 80-93.
[http://dx.doi.org/10.5492/wjccm.v1.i3.80] [PMID: 24701405]
[2]
Yoo, S.; Lee, H.B.; Han, W.; Noh, D.Y.; Park, S.K.; Kim, W.H.; Kim, J.T. Total intravenous anesthesia versus inhalation anesthesia for breast cancer surgery. Anesthesiology, 2019, 130(1), 31-40.
[http://dx.doi.org/10.1097/ALN.0000000000002491] [PMID: 30376457]
[3]
Goh, A.C.N.; Bagshaw, O.; Courtman, S. A follow-up survey of total intravenous anesthesia usage in children in the U.K. and Ireland. Paediatr. Anaesth., 2019, 29(2), 180-185.
[http://dx.doi.org/10.1111/pan.13556] [PMID: 30472794]
[4]
Eleveld, D.J.; Colin, P.; Absalom, A.R.; Struys, M.M.R.F. Target-controlled-infusion models for remifentanil dosing consistent with approved recommendations. Br. J. Anaesth., 2020, 125(4), 483-491.
[http://dx.doi.org/10.1016/j.bja.2020.05.051] [PMID: 32654750]
[5]
Anderson, B.J.; Bagshaw, O. Practicalities of total intravenous anesthesia and target-controlled infusion in children. Anesthesiology, 2019, 131(1), 164-185.
[http://dx.doi.org/10.1097/ALN.0000000000002657] [PMID: 30920966]
[6]
Struys, M.M.R.F.; De Smet, T.; Glen, J.I.B.; Vereecke, H.E.M.; Absalom, A.R.; Schnider, T.W. The history of target-controlled infusion. Anesth. Analg., 2016, 122(1), 56-69.
[http://dx.doi.org/10.1213/ANE.0000000000001008] [PMID: 26516804]
[7]
Chidambaran, V.; Costandi, A.; D’Mello, A. Propofol: a review of its role in pediatric anesthesia and sedation. CNS Drugs, 2015, 29(7), 543-563.
[http://dx.doi.org/10.1007/s40263-015-0259-6] [PMID: 26290263]
[8]
Marik, P. Propofol: therapeutic indications and side-effects. Curr. Pharm. Des., 2004, 10(29), 3639-3649.
[http://dx.doi.org/10.2174/1381612043382846] [PMID: 15579060]
[9]
Yuki, K.; Bu, W.; Eckenhoff, R.G.; Yokomizo, T.; Okuno, T.; Yuki, K. The role of propofol hydroxyl group in 5-lipoxygenase recognition. Biochem. Biophys. Res. Commun., 2020, 525(4), 909-914.
[http://dx.doi.org/10.1016/j.bbrc.2020.03.037] [PMID: 32171526]
[10]
Vanlersberghe, C.; Camu, F. Propofol. Handb. Exp. Pharmacol., 2008, 182(182), 227-252.
[http://dx.doi.org/10.1007/978-3-540-74806-9_11] [PMID: 18175094]
[11]
Sahinovic, M.M.; Struys, M.M.R.F.; Absalom, A.R. Clinical pharmacokinetics and pharmacodynamics of propofol. Clin. Pharmacokinet., 2018, 57(12), 1539-1558.
[http://dx.doi.org/10.1007/s40262-018-0672-3] [PMID: 30019172]
[12]
Absalom, A.R.; Mani, V.; De Smet, T.; Struys, M.M.R.F. Pharmacokinetic models for propofol—defining and illuminating the devil in the detail. Br. J. Anaesth., 2009, 103(1), 26-37.
[http://dx.doi.org/10.1093/bja/aep143] [PMID: 19520702]
[13]
Feldman, P.L. Insights into the chemical discovery of remifentanil. Anesthesiology, 2020, 132(5), 1229-1234.
[http://dx.doi.org/10.1097/ALN.0000000000003170] [PMID: 32028373]
[14]
Santonocito, C.; Noto, A.; Crimi, C.; Sanfilippo, F. Remifentanil-induced postoperative hyperalgesia: current perspectives on mechanisms and therapeutic strategies. Local Reg. Anesth., 2018, 11, 15-23.
[http://dx.doi.org/10.2147/LRA.S143618] [PMID: 29670398]
[15]
Yu, E.H.Y.; Tran, D.H.D.; Lam, S.W.; Irwin, M.G. Remifentanil tolerance and hyperalgesia: short-term gain, long-term pain? Anaesthesia, 2016, 71(11), 1347-1362.
[http://dx.doi.org/10.1111/anae.13602] [PMID: 27734470]
[16]
Fletcher, D.; Martinez, V. Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis. Br. J. Anaesth., 2014, 112(6), 991-1004.
[http://dx.doi.org/10.1093/bja/aeu137] [PMID: 24829420]
[17]
Gunasekaran, T.; Haile, T.; Nigusse, T.; Dhanaraju, M.D. Nanotechnology: an effective tool for enhancing bioavailability and bioactivity of phytomedicine. Asian Pac. J. Trop. Biomed., 2014, 4(Suppl. 1), S1-S7.
[http://dx.doi.org/10.12980/APJTB.4.2014C980] [PMID: 25183064]
[18]
Joye, I.J.; Davidov-Pardo, G.; McClements, D.J. Nanotechnology for increased micronutrient bioavailability. Trends Food Sci. Technol., 2014, 40(2), 168-182.
[http://dx.doi.org/10.1016/j.tifs.2014.08.006]
[19]
Shin, G.H.; Kim, J.T.; Park, H.J. Recent developments in nanoformulations of lipophilic functional foods. Trends Food Sci. Technol., 2015, 46(1), 144-157.
[http://dx.doi.org/10.1016/j.tifs.2015.07.005]
[20]
Zorzi, G.K.; Carvalho, E.L.S.; von Poser, G.L.; Teixeira, H.F. On the use of nanotechnology-based strategies for association of complex matrices from plant extracts. Rev. Bras. Farmacogn., 2015, 25(4), 426-436.
[http://dx.doi.org/10.1016/j.bjp.2015.07.015]
[21]
McClements, D.J. Emulsion design to improve the delivery of functional lipophilic components. Annu. Rev. Food Sci. Technol., 2010, 1(1), 241-269.
[http://dx.doi.org/10.1146/annurev.food.080708.100722] [PMID: 22129337]
[22]
Singh, Y.; Meher, J.G.; Raval, K.; Khan, F.A.; Chaurasia, M.; Jain, N.K.; Chourasia, M.K. Nanoemulsion: Concepts, development and applications in drug delivery. J. Control. Release, 2017, 252, 28-49.
[http://dx.doi.org/10.1016/j.jconrel.2017.03.008] [PMID: 28279798]
[23]
Pandey, P.; Gulati, N.; Makhija, M.; Purohit, D.; Dureja, H. Nanoemulsion: A novel drug delivery approach for enhancement of bioavailability. Recent Pat. Nanotechnol., 2020, 14(4), 276-293.
[http://dx.doi.org/10.2174/1872210514666200604145755] [PMID: 32496999]
[24]
Xiao, W.; Zhao, Y.; Yang, J.; Ren, Y.; Yang, W.; Huang, X.; Zhang, L. Effect of sodium oleate on the adsorption morphology and mechanism of nanobubbles on the mica surface. Langmuir, 2019, 35(28), 9239-9245.
[http://dx.doi.org/10.1021/acs.langmuir.9b01384] [PMID: 31268336]
[25]
Chen, L.H.; Cheng, L.C.; Doyle, P.S. Nanoemulsion-loaded capsules for controlled delivery of lipophilic active ingredients. Adv. Sci. (Weinh.), 2020, 7(20), 2001677.
[http://dx.doi.org/10.1002/advs.202001677] [PMID: 33101868]
[26]
Lauder, G.R. Total intravenous anesthesia will supercede inhalational anesthesia in pediatric anesthetic practice. Paediatr. Anaesth., 2015, 25(1), 52-64.
[http://dx.doi.org/10.1111/pan.12553] [PMID: 25312700]
[27]
Berry, S.H. Injectable anesthetics. In: Veterinary anesthesia and analgesia—the fifth edition of Lumb and Jones; Grimm, K.A.; Lamont, L.A.; Tranquilli, W.J.; Greene, S.A.; Robertson, S.A., Eds.; Wiley: Ames Iowa, 2015; pp. 559-583.
[http://dx.doi.org/10.1002/9781119421375.ch15]
[28]
Servin, F.S.; Billard, V. Remifentanil and other opioids. Handb. Exp. Pharmacol., 2008, 182(182), 283-311.
[http://dx.doi.org/10.1007/978-3-540-74806-9_14] [PMID: 18175097]

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