Abstract
Background: Growing public awareness of chronic pain resulting from illness and injury has prompted pharmaceutical researchers and drug corporations to create better, more targeted painkillers. For effective pain management, prolonged analgesic medication delivery at the intended areas continues to be a major problem such as addiction, tolerance and other serious side effects, which can prolong suffering and decrease painkiller effectiveness.
Objective: The present paper focuses on review of current advances in the field of pain treatment by different nanoparticles formulations of various drugs, by enhancing their pharmacokinetic factors and diminishing associated adverse effects.
Results: According to literature survey, usage of nano-carriers enables the delivery of these drugs to target locations with less systemic toxicity. Nanotechnology for varied therapeutic purposes, different analgesics have been loaded onto different nano carriers, including those that are natural, synthetic, and polymeric and proven to be beneficial in pain management.
Conclusion: Overall, new nano based preparations and new ways to utilize existing medications in a variety of circumstances is a multimodal approach to pain relief, have resulted in recent advancements in the pharmacological management of pain.
Graphical Abstract
[1]
Van Rensburg R, Reuter H. An overview of analgesics: NSAIDs, paracetamol, and topical analgesics. S Afr Fam Pract 2019; 61(1): 6-12. (DOI: 10.1080/20786190.2019.1610228).
[http://dx.doi.org/10.4102/safp.v61i1.5045]
[http://dx.doi.org/10.4102/safp.v61i1.5045]
[2]
Cazacu I, Mogosan C, Loghin F. Safety issues of current analgesics: An update. Clujul Med 2015; 88(2): 128-36.
[http://dx.doi.org/10.15386/cjmed-413] [PMID: 26528060]
[http://dx.doi.org/10.15386/cjmed-413] [PMID: 26528060]
[3]
Dorner TE. Pain and chronic pain epidemiology. Wien Klin Wochenschr 2018; 130(1-2): 1-3.
[http://dx.doi.org/10.1007/s00508-017-1301-0] [PMID: 29270720]
[http://dx.doi.org/10.1007/s00508-017-1301-0] [PMID: 29270720]
[4]
van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology and its clinical relevance. Br J Anaesth 2013; 111(1): 13-8.
[http://dx.doi.org/10.1093/bja/aet123] [PMID: 23794640]
[http://dx.doi.org/10.1093/bja/aet123] [PMID: 23794640]
[5]
Doody O, Bailey ME. Understanding pain physiology and its application to person with intellectual disability. J Intellect Disabil 2019; 23(1): 5-18.
[http://dx.doi.org/10.1177/1744629517708680] [PMID: 28502222]
[http://dx.doi.org/10.1177/1744629517708680] [PMID: 28502222]
[6]
Das V. An introduction to pain pathways and pain “targets”. Prog Mol Biol Transl Sci 2015; 131: 1-30.
[http://dx.doi.org/10.1016/bs.pmbts.2015.01.003] [PMID: 25744668]
[http://dx.doi.org/10.1016/bs.pmbts.2015.01.003] [PMID: 25744668]
[7]
Karunanayake Aranjan L. Risk factors for chronic low back pain. J Community Med Health Educ 2014; 4(2): 1-4.
[http://dx.doi.org/10.4172/2161-0711.1000271]
[http://dx.doi.org/10.4172/2161-0711.1000271]
[8]
Tavares DRB, Trevisani ZFM, Okazaki JEF, et al. Risk factors of pain, physical function, and health-related quality of life in elderly people with knee osteoarthritis: A cross-sectional study. Heliyon 2020; 6(12): e05723.
[http://dx.doi.org/10.1016/j.heliyon.2020.e05723]
[http://dx.doi.org/10.1016/j.heliyon.2020.e05723]
[9]
van Hecke O, Torrance N, Smith BH. Chronic pain epidemiology: Where do lifestyle factors fit in? Br J Pain 2013; 7(4): 209-17.
[http://dx.doi.org/10.1177/2049463713493264] [PMID: 26516524]
[http://dx.doi.org/10.1177/2049463713493264] [PMID: 26516524]
[10]
Schuler M, Njoo N, Hestermann M, Oster P, Hauer K. Acute and chronic pain in geriatrics: Clinical characteristics of pain and the influence of cognition. Pain Med 2004; 5(3): 253-62.
[http://dx.doi.org/10.1111/j.1526-4637.2004.04040.x] [PMID: 15367303]
[http://dx.doi.org/10.1111/j.1526-4637.2004.04040.x] [PMID: 15367303]
[11]
Treede RD, Rief W, Barke A, et al. A classification of chronic pain for ICD-11. Pain 2015; 156(6): 1003-7.
[http://dx.doi.org/10.1097/j.pain.0000000000000160] [PMID: 25844555]
[http://dx.doi.org/10.1097/j.pain.0000000000000160] [PMID: 25844555]
[12]
Borsook D. Neurological diseases and pain. Brain 2012; 135(2): 320-44.
[http://dx.doi.org/10.1093/brain/awr271] [PMID: 22067541]
[http://dx.doi.org/10.1093/brain/awr271] [PMID: 22067541]
[14]
de Heer EW, Gerrits MMJG, Beekman ATF, et al. The association of depression and anxiety with pain: A study from NESDA. PLoS One 2014; 9(10): e106907.
[http://dx.doi.org/10.1371/journal.pone.0106907] [PMID: 25330004]
[http://dx.doi.org/10.1371/journal.pone.0106907] [PMID: 25330004]
[15]
Moradkhani MR, Karimi A, Negahdari B. Nanotechnology application for pain therapy. Artif Cells Nanomed Biotechnol 2018; 46(2): 368-73.
[http://dx.doi.org/10.1080/21691401.2017.1313265] [PMID: 28395516]
[http://dx.doi.org/10.1080/21691401.2017.1313265] [PMID: 28395516]
[16]
Bhansali D, Teng SL, Lee CS, Schmidt BL, Bunnett NW, Leong KW. Nanotechnology for pain management: Current and future therapeutic interventions. Nano Today 2021; 39: 101223.
[http://dx.doi.org/10.1016/j.nantod.2021.101223] [PMID: 34899962]
[http://dx.doi.org/10.1016/j.nantod.2021.101223] [PMID: 34899962]
[17]
Hulla JE, Sahu SC, Hayes AW. Nanotechnology. Hum Exp Toxicol 2015; 34(12): 1318-21.
[http://dx.doi.org/10.1177/0960327115603588] [PMID: 26614822]
[http://dx.doi.org/10.1177/0960327115603588] [PMID: 26614822]
[18]
Douglas D. Pharmaceutical nanotechnology: A therapeutic revolution. Int J Pharm Sci Res 2020; 6(1): 009-11.
[http://dx.doi.org/10.17352/ijpsdr.000027]
[http://dx.doi.org/10.17352/ijpsdr.000027]
[19]
Patra JK, Das G, Fraceto LF, et al. Nano based drug delivery systems: Recent developments and future prospects. J Nanobiotechnology 2018; 16(1): 71-5.
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[http://dx.doi.org/10.1186/s12951-018-0392-8] [PMID: 30231877]
[20]
Kargozar S, Mozafari M. Nanotechnology and Nanomedicine: Start small, think big. Mater Today Proc 2018; 5(7): 15492-500.
[http://dx.doi.org/10.1016/j.matpr.2018.04.155]
[http://dx.doi.org/10.1016/j.matpr.2018.04.155]
[21]
Shi J, Votruba AR, Farokhzad OC, Langer R. Nanotechnology in drug delivery and tissue engineering: From discovery to applications. Nano Lett 2010; 10(9): 3223-30.
[http://dx.doi.org/10.1021/nl102184c] [PMID: 20726522]
[http://dx.doi.org/10.1021/nl102184c] [PMID: 20726522]
[22]
Hamidi M, Azadi A, Rafiei P. Hydrogel nanoparticles in drug delivery. Adv Drug Deliv Rev 2008; 60(15): 1638-49.
[http://dx.doi.org/10.1016/j.addr.2008.08.002] [PMID: 18840488]
[http://dx.doi.org/10.1016/j.addr.2008.08.002] [PMID: 18840488]
[23]
Chirani N, Yahia L, Gritsch L, et al. History and application of hydrogels. J Biomed Sci 2015; 4: 1-23.
[http://dx.doi.org/10.4172/2254-609X.100013]
[http://dx.doi.org/10.4172/2254-609X.100013]
[24]
dos Santos AC, Akkari ACS, Ferreira IRS, et al. Poloxamer-based binary hydrogels for delivering tramadol hydrochloride: Sol-gel transition studies, dissolution-release kinetics, in vitro toxicity, and pharmacological evaluation. Int J Nanomedicine 2015; 10: 2391-401.
[http://dx.doi.org/10.2147/IJN.S72337] [PMID: 25848258]
[http://dx.doi.org/10.2147/IJN.S72337] [PMID: 25848258]
[25]
Li X, Du L, Chen X, et al. Nasal delivery of analgesic ketorolac tromethamine thermo- and ion-sensitive in situ hydrogels. Int J Pharm 2015; 489(1-2): 252-60.
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.009] [PMID: 25957699]
[http://dx.doi.org/10.1016/j.ijpharm.2015.05.009] [PMID: 25957699]
[26]
Yokoyama M. Polymeric micelles as drug carriers: Their lights and shadows. J Drug Target 2014; 22(7): 576-83.
[http://dx.doi.org/10.3109/1061186X.2014.934688] [PMID: 25012065]
[http://dx.doi.org/10.3109/1061186X.2014.934688] [PMID: 25012065]
[27]
Yokoyama M. Clinical applications of polymeric micelle carrier systems in chemotherapy and image diagnosis of solid tumors. J Exp Clin Med 2011; 3(4): 151-8.
[http://dx.doi.org/10.1016/j.jecm.2011.06.002]
[http://dx.doi.org/10.1016/j.jecm.2011.06.002]
[28]
Prencipe F, Diaferia C, Rossi F, Ronga L, Tesauro D. Forward precision medicine: Micelles for active targeting driven by peptides. Molecules 2021; 26(13): 4049.
[http://dx.doi.org/10.3390/molecules26134049] [PMID: 34279392]
[http://dx.doi.org/10.3390/molecules26134049] [PMID: 34279392]
[29]
Aziz ZAA, Nasir HM, Ahmad A, et al. Enrichment of eucalyptus oil nanoemulsion by micellar nanotechnology: Transdermal analgesic activity using hot plate test in rats’ assay. Sci Rep 2019; 9(1): 13678.
[http://dx.doi.org/10.1038/s41598-019-50134-y] [PMID: 31548590]
[http://dx.doi.org/10.1038/s41598-019-50134-y] [PMID: 31548590]
[30]
Banerjee R. Liposomes: Applications in medicine. J Biomater Appl 2001; 16(1): 3-21.
[http://dx.doi.org/10.1106/RA7U-1V9C-RV7C-8QXL] [PMID: 11475357]
[http://dx.doi.org/10.1106/RA7U-1V9C-RV7C-8QXL] [PMID: 11475357]
[31]
Shivhare U, Mathur V, Bhusari K, et al. Formulation and evaluation of pentoxifylline liposome formulation. Dig J Nanomater Biostruct 2009; 4(4): 857-62.
[32]
Iwaszkiewicz KS, Hua S. Development of an effective topical liposomal formulation for localized analgesia and anti-inflammatory actions in the complete freund’s adjuvant rodent model of acute inflammatory pain. Pain Physician 2014; 17(6): E719-35.
[PMID: 25415787]
[PMID: 25415787]
[33]
Grant GJ, Barenholz Y, Bolotin EM, et al. A novel liposomal bupivacaine formulation to produce ultralong: Acting analgesia. Anesthesiology 2004; 101(1): 133-7.
[http://dx.doi.org/10.1097/00000542-200407000-00021] [PMID: 15220782]
[http://dx.doi.org/10.1097/00000542-200407000-00021] [PMID: 15220782]
[34]
Puri A, Loomis K, Smith B, et al. Lipid-based nanoparticles as pharmaceutical drug carriers: From concepts to clinic. Crit Rev Ther Drug Carrier Syst 2009; 26(6): 523-80.
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i6.10] [PMID: 20402623]
[http://dx.doi.org/10.1615/CritRevTherDrugCarrierSyst.v26.i6.10] [PMID: 20402623]
[35]
Scioli Montoto S, Muraca G, Ruiz ME. Solid lipid nanoparticles for drug delivery: Pharmacological and biopharmaceutical aspects. Front Mol Biosci 2020; 7: 587997.
[http://dx.doi.org/10.3389/fmolb.2020.587997] [PMID: 33195435]
[http://dx.doi.org/10.3389/fmolb.2020.587997] [PMID: 33195435]
[36]
Dandagi PM, Dessai GA, Gadad AP, et al. Formulation and evaluation of nanostructured lipid carrier (NLC) of lornoxicam. Int J Pharma Sci 2014; 6(2): 73-7. [Corpus ID: 59400803].
[37]
Yang Y, Qiu D, Liu Y, Chao L. Topical anesthetic analgesic therapy using the combination of ropivacaine and dexmedetomidine: Hyaluronic acid modified long-acting nanostructured lipid carriers containing a skin penetration enhancer. Drug Des Devel Ther 2019; 13: 3307-19.
[http://dx.doi.org/10.2147/DDDT.S211443] [PMID: 31571832]
[http://dx.doi.org/10.2147/DDDT.S211443] [PMID: 31571832]
[38]
Tayeb HH, Sainsbury F. Nanoemulsions in drug delivery: Formulation to medical application. Nanomedicine 2018; 13(19): 2507-25.
[http://dx.doi.org/10.2217/nnm-2018-0088] [PMID: 30265218]
[http://dx.doi.org/10.2217/nnm-2018-0088] [PMID: 30265218]
[39]
Wang JJ, Hung CF, Yeh CH, Fang JY. The release and analgesic activities of morphine and its ester prodrug, morphine propionate, formulated by water-in-oil nanoemulsions. J Drug Target 2008; 16(4): 294-301.
[http://dx.doi.org/10.1080/10611860801900090] [PMID: 18446608]
[http://dx.doi.org/10.1080/10611860801900090] [PMID: 18446608]
[40]
Tang SY, Sivakumar M, Ng AMH, Shridharan P. Anti-inflammatory and analgesic activity of novel oral aspirin-loaded nanoemulsion and nano multiple emulsion formulations generated using ultrasound cavitation. Int J Pharm 2012; 430(1-2): 299-306.
[http://dx.doi.org/10.1016/j.ijpharm.2012.03.055] [PMID: 22503988]
[http://dx.doi.org/10.1016/j.ijpharm.2012.03.055] [PMID: 22503988]
[41]
Ghiasi Z, Esmaeli F, Aghajani M, Ghazi-Khansari M, Faramarzi MA, Amani A. Enhancing analgesic and anti-inflammatory effects of capsaicin when loaded into olive oil nanoemulsion: An in vivo study. Int J Pharm 2019; 559: 341-7.
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.043] [PMID: 30710660]
[http://dx.doi.org/10.1016/j.ijpharm.2019.01.043] [PMID: 30710660]
[42]
Liong M, Lu J, Kovochich M, et al. Multifunctional inorganic nanoparticles for imaging, targeting, and drug delivery. ACS Nano 2008; 2(5): 889-96.
[http://dx.doi.org/10.1021/nn800072t] [PMID: 19206485]
[http://dx.doi.org/10.1021/nn800072t] [PMID: 19206485]
[43]
Paul W, Sharma CP. Inorganic nanoparticles for targeted drug delivery. Bioint Med Implant Mat 2020; 2: 333-64.
[http://dx.doi.org/10.1016/B978-0-08-102680-9.00013-5]
[http://dx.doi.org/10.1016/B978-0-08-102680-9.00013-5]
[44]
Giljohann DA, Seferos DS, Daniel WL, Massich MD, Patel PC, Mirkin CA. Gold nanoparticles for biology and medicine. Angew Chem Int Ed 2010; 49(19): 3280-94.
[http://dx.doi.org/10.1002/anie.200904359] [PMID: 20401880]
[http://dx.doi.org/10.1002/anie.200904359] [PMID: 20401880]
[45]
Dykman LA, Khlebtsov NG. Gold nanoparticles in biology and medicine: Recent advances and prospects. Acta Nat 2011; 3(2): 34-55.
[http://dx.doi.org/10.32607/20758251-2011-3-2-34-55] [PMID: 22649683]
[http://dx.doi.org/10.32607/20758251-2011-3-2-34-55] [PMID: 22649683]
[46]
Murad U. Barkatullah, Khan SA, Ibrar M, Ullah S, Khattak U. Synthesis of silver and gold nanoparticles from leaf of Litchi chinensis and its biological activities. Asian Pac J Trop Biomed 2018; 8(3): 142-9.
[http://dx.doi.org/10.4103/2221-1691.227995]
[http://dx.doi.org/10.4103/2221-1691.227995]
[47]
Khuda F, Ul Haq Z, Ilahi I, et al. Synthesis of gold nanoparticles using Sambucus wightiana extract and investigation of its antimicrobial, anti-inflammatory, antioxidant and analgesic activities. Arab J Chem 2021; 14(10): 103343.
[http://dx.doi.org/10.1016/j.arabjc.2021.103343]
[http://dx.doi.org/10.1016/j.arabjc.2021.103343]
[48]
Slowing II, Trewyn BG, Giri S, Lin VS-Y. Mesoporous silica nanoparticles for drug delivery and biosensing applications. Adv Funct Mater 2007; 17(8): 1225-36.
[http://dx.doi.org/10.1002/adfm.200601191]
[http://dx.doi.org/10.1002/adfm.200601191]
[49]
Castillo RR, Lozano D, González B, Manzano M, Izquierdo-Barba I, Vallet-Regí M. Advances in mesoporous silica nanoparticles for targeted stimuli-responsive drug delivery: An update. Expert Opin Drug Deliv 2019; 16(4): 415-39.
[http://dx.doi.org/10.1080/17425247.2019.1598375] [PMID: 30897978]
[http://dx.doi.org/10.1080/17425247.2019.1598375] [PMID: 30897978]
[50]
Xie J, Xiao D, Zhao J, et al. Mesoporous silica particles as a multifunctional delivery system for pain relief in experimental neuropathy. Adv Healthc Mater 2016; 5(10): 1213-21.
[http://dx.doi.org/10.1002/adhm.201500996] [PMID: 27028159]
[http://dx.doi.org/10.1002/adhm.201500996] [PMID: 27028159]
[51]
Dobson J. Magnetic nanoparticles for drug delivery. Drug Dev Res 2006; 67(1): 55-60.
[http://dx.doi.org/10.1002/ddr.20067]
[http://dx.doi.org/10.1002/ddr.20067]
[52]
Wu PC, Hsiao HT, Lin YC, Shieh DB, Liu YC. The analgesia efficiency of ultrasmall magnetic iron oxide nanoparticles in mice chronic inflammatory pain model. Nanomedicine 2017; 13(6): 1975-81.
[http://dx.doi.org/10.1016/j.nano.2017.05.005] [PMID: 28539274]
[http://dx.doi.org/10.1016/j.nano.2017.05.005] [PMID: 28539274]
[53]
Liu H, Zhang R, Liang G. Effect of ropivacaine-loaded magnetic nanoparticles on ankle nerve block in rats. Comput Math Methods Med 2021; 2021: 1-6.
[http://dx.doi.org/10.1155/2021/8553015] [PMID: 34899971]
[http://dx.doi.org/10.1155/2021/8553015] [PMID: 34899971]
[54]
Ziental D, Czarczynska-Goslinska B, Mlynarczyk DT, et al. Titanium dioxide nanoparticles: Prospects and applications in medicine. Nanomaterials 2020; 10(2): 387.
[http://dx.doi.org/10.3390/nano10020387] [PMID: 32102185]
[http://dx.doi.org/10.3390/nano10020387] [PMID: 32102185]
