Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Review Article

Therapeutic Effects of Statins: Promising Drug for Topical and Transdermal Administration

Author(s): Fatemeh Zahedipour, Seyede Atefe Hosseini, Željko Reiner, Eugenia Tedeschi-Reiner, Tannaz Jamialahmadi and Amirhossein Sahebkar*

Volume 31, Issue 21, 2024

Published on: 26 June, 2023

Page: [3149 - 3166] Pages: 18

DOI: 10.2174/0929867330666230508141434

Price: $65

Open Access Journals Promotions 2
conference banner
Abstract

Statins are HMG-CoA reductase inhibitors and decrease plasma low-density lipoprotein cholesterol (LDL-C) levels. They are well tolerated, and because of their LDL-C-lowering effect, they are utilized to decrease the risk of atherosclerosis and cardiovascular disease. However, statins have pleiotropic effects, including immunomodulatory, anti-inflammatory, antioxidant, and anticancer. Currently, oral administration is the only Food and Drug Administration (FDA)-approved route of administration for statins. However, other administration routes have demonstrated promising results in different pre-clinical and clinical studies. For instance, statins also seem beneficial in dermatitis, psoriasis, vitiligo, hirsutism, uremic pruritus, and graft-versus-host disease. Topically applied statins have been studied to treat seborrhea, acne, rhinophyma, and rosacea. They also have beneficial effects in contact dermatitis and wound healing in animal studies, (HIV) infection, osseointegration, porokeratosis, and some ophthalmologic diseases. Topical and transdermal application of statins is a non-invasive drug administration method that has shown significant results in bypassing the first-pass metabolism in the liver, thereby reducing possible adverse effects. This study reviews the multifaceted molecular and cellular impacts of statins, their topical and transdermal application, novel delivery systems, such as nanosystems for topical and transdermal administration and the challenges concerning this approach.

Keywords: Statins, topical delivery, transdermal delivery, therapeutic effects, HMG-CoA, LDL-C.

« Previous Next »
[1]
Bedi, O.; Dhawan, V.; Sharma, P.L.; Kumar, P. Pleiotropic effects of statins: new therapeutic targets in drug design. Naunyn Schmiedebergs Arch. Pharmacol., 2016, 389(7), 695-712.
[http://dx.doi.org/10.1007/s00210-016-1252-4] [PMID: 27146293]
[2]
Bahrami, A.; Bo, S.; Jamialahmadi, T.; Sahebkar, A. Effects of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on ageing: Molecular mechanisms. Ageing Res. Rev., 2020, 58, 101024.
[http://dx.doi.org/10.1016/j.arr.2020.101024] [PMID: 32006687]
[3]
Bland, A.R.; Payne, F.M.; Ashton, J.C.; Jamialahmadi, T.; Sahebkar, A. The cardioprotective actions of statins in targeting mitochondrial dysfunction associated with myocardial ischaemia-reperfusion injury. Pharmacol. Res., 2022, 175, 105986.
[http://dx.doi.org/10.1016/j.phrs.2021.105986] [PMID: 34800627]
[4]
Ferretti, G.; Bacchetti, T.; Sahebkar, A. Effect of statin therapy on paraoxonase-1 status: A systematic review and meta-analysis of 25 clinical trials. Prog. Lipid Res., 2015, 60, 50-73.
[http://dx.doi.org/10.1016/j.plipres.2015.08.003] [PMID: 26416579]
[5]
Parizadeh, S.M.R.; Azarpazhooh, M.R.; Moohebati, M.; Nematy, M.; Ghayour-Mobarhan, M.; Tavallaie, S.; Rahsepar, A.A.; Amini, M.; Sahebkar, A.; Mohammadi, M.; Ferns, G.A.A. Simvastatin therapy reduces prooxidant-antioxidant balance: results of a placebo-controlled cross-over trial. Lipids, 2011, 46(4), 333-340.
[http://dx.doi.org/10.1007/s11745-010-3517-x] [PMID: 21207250]
[6]
Sahebkar, A.; Chew, G.T.; Watts, G.F. Recent advances in pharmacotherapy for hypertriglyceridemia. Prog. Lipid Res. , 2014, 56(1), 47-66.
[http://dx.doi.org/10.1016/j.plipres.2014.07.002] [PMID: 25083925]
[7]
Koushki, K., Shahbaz, S. K., Mashayekhi, K., Sadeghi, M., Zayeri, Z. D., Taba, M. Y., Banach, M., Al-Rasadi, K., Johnston, T. P., & Sahebkar, A. Anti-inflammatory action of statins in cardiovascular disease: The role of inflammasome and toll-Like receptor pathways. Clinical reviews in allergy & immunology,, 2021, 60(2), 175–199.
[http://dx.doi.org/10.1007/s12016-020-08791-9]
[8]
Sahebkar, A.; Serban, C.; Mikhailidis, D.P.; Undas, A.; Lip, G.Y.H.; Muntner, P.; Bittner, V.; Ray, K.K.; Watts, G.F.; Hovingh, G.K.; Rysz, J.; Kastelein, J.J.; Banach, M. Association between statin use and plasma D-dimer levels. A systematic review and meta-analysis of randomised controlled trials. Thromb. Haemost., 2015, 114(3), 546-557.
[PMID: 26017749]
[9]
Sohrevardi, S.; Nasab, F.; Mirjalili, M.; Bagherniya, M.; Tafti, A.; Jarrahzadeh, M.; Azarpazhooh, M.; Saeidmanesh, M.; Banach, M.; Jamialahmadi, T.; Sahebkar, A. Effect of atorvastatin on delirium status of patients in the intensive care unit: A randomized controlled trial. Arch. Med. Sci., 2019, 17(5), 1423-1428.
[http://dx.doi.org/10.5114/aoms.2019.89330] [PMID: 34522273]
[10]
Greenwood, J.; Steinman, L.; Zamvil, S.S. Statin therapy and autoimmune disease: From protein prenylation to immunomodulation. Nat. Rev. Immunol., 2006, 6(5), 358-370.
[http://dx.doi.org/10.1038/nri1839] [PMID: 16639429]
[11]
Davignon, J. Pleiotropic effects of pitavastatin. Br. J. Clin. Pharmacol., 2012, 73(4), 518-535.
[http://dx.doi.org/10.1111/j.1365-2125.2011.04139.x] [PMID: 22053916]
[12]
Viola, G.; Grobelny, P.; Linardi, M.A.; Salvador, A.; Dall’Acqua, S.; Sobotta, Ł.; Mielcarek, J.; Dall’Acqua, F.; Vedaldi, D.; Basso, G. Pitavastatin, a new HMG-CoA reductase inhibitor, induces phototoxicity in human keratinocytes NCTC-2544 through the formation of benzophenanthridine-like photoproducts. Arch. Toxicol., 2012, 86(3), 483-496.
[http://dx.doi.org/10.1007/s00204-011-0772-4] [PMID: 22038141]
[13]
Li, J.; Wang, Y.; Zhang, W.; Huang, Y.; Hein, K.; Hidalgo, I.J. The role of a basolateral transporter in rosuvastatin transport and its interplay with apical breast cancer resistance protein in polarized cell monolayer systems. Drug Metab. Dispos., 2012, 40(11), 2102-2108.
[http://dx.doi.org/10.1124/dmd.112.045666] [PMID: 22855735]
[14]
Bytyçi, I.; Penson, P.E.; Mikhailidis, D.P.; Wong, N.D.; Hernandez, A.V.; Sahebkar, A.; Thompson, P.D.; Mazidi, M.; Rysz, J.; Pella, D.; Reiner, Ž.; Toth, P.P.; Banach, M. Prevalence of statin intolerance: A meta-analysis. Eur. Heart J., 2022, 43(34), 3213-3223.
[http://dx.doi.org/10.1093/eurheartj/ehac015] [PMID: 35169843]
[15]
Ward, N.C.; Watts, G.F.; Eckel, R.H. Statin toxicity. Circ. Res., 2019, 124(2), 328-350.
[http://dx.doi.org/10.1161/CIRCRESAHA.118.312782] [PMID: 30653440]
[16]
Banach, M.; Serban, C.; Ursoniu, S.; Rysz, J.; Muntner, P.; Toth, P.P.; Jones, S.R.; Rizzo, M.; Glasser, S.P.; Watts, G.F.; Blumenthal, R.S.; Lip, G.Y.H.; Mikhailidis, D.P.; Sahebkar, A. Statin therapy and plasma coenzyme Q10 concentrations—A systematic review and meta-analysis of placebo-controlled trials. Pharmacol. Res., 2015, 99, 329-336.
[http://dx.doi.org/10.1016/j.phrs.2015.07.008] [PMID: 26192349]
[17]
Tobert, J.A. Lovastatin and beyond: The history of the HMG-CoA reductase inhibitors. Nat. Rev. Drug Discov., 2003, 2(7), 517-526.
[http://dx.doi.org/10.1038/nrd1112] [PMID: 12815379]
[18]
Reiner, Ž. Statins in the primary prevention of cardiovascular disease. Nat. Rev. Cardiol., 2013, 10(8), 453-464.
[http://dx.doi.org/10.1038/nrcardio.2013.80] [PMID: 23736519]
[19]
Ostrowski, S.M.; Johnson, K.; Siefert, M.; Shank, S.; Sironi, L.; Wolozin, B.; Landreth, G.E.; Ziady, A.G. Simvastatin inhibits protein isoprenylation in the brain. Neuroscience, 2016, 329, 264-274.
[http://dx.doi.org/10.1016/j.neuroscience.2016.04.053] [PMID: 27180285]
[20]
Abrahamson, E.E.; Ikonomovic, M.D.; Dixon, C.E.; DeKosky, S.T. Simvastatin therapy prevents brain trauma-induced increases in β-amyloid peptide levels. Ann. Neurol., 2009, 66(3), 407-414.
[http://dx.doi.org/10.1002/ana.21731] [PMID: 19798641]
[21]
Ostad, S.N.; Afzali, M.; Vatankhah, M. Investigation of simvastatin-induced apoptosis and cell cycle arrest in cancer stem cells of MCF-7. J. Cancer Res. Ther., 2016, 12(2), 725-730.
[http://dx.doi.org/10.4103/0973-1482.146127] [PMID: 27461641]
[22]
Kim, Y.; Kim, T.W.; Han, S.W.; Ahn, J.B.; Kim, S.T.; Lee, J.; Park, J.O.; Park, Y.S.; Lim, H.Y.; Kang, W.K. A single arm, phase II study of simvastatin plus XELOX and bevacizumab as first-line chemotherapy in metastatic colorectal cancer patients. Cancer Res. Treat., 2019, 51(3), 1128-1134.
[http://dx.doi.org/10.4143/crt.2018.379] [PMID: 30477287]
[23]
Li, N.; Xie, X.; Hu, Y.; He, H.; Fu, X.; Fang, T.; Li, C. Herceptin-conjugated liposomes co-loaded with doxorubicin and simvastatin in targeted prostate cancer therapy. Am. J. Transl. Res., 2019, 11(3), 1255-1269.
[PMID: 30972160]
[24]
Luput, L.; Sesarman, A.; Porfire, A.; Achim, M.; Muntean, D.; Casian, T.; Patras, L.; Rauca, V.F.; Drotar, D.M.; Stejerean, I.; Tomuta, I.; Vlase, L.; Dragos, N.; Toma, V.A.; Licarete, E.; Banciu, M. Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5-fluorouracil in vivo. Cancer Sci., 2020, 111(4), 1344-1356.
[http://dx.doi.org/10.1111/cas.14312] [PMID: 31960547]
[25]
Lin, T-K; Chou, P; Lin, C-H; Hung, Y-J; Jong, G-P Long-term effect of statins on the risk of new-onset osteoporosis: A nationwide population-based cohort study. PLoS One, 2018, 13(5), e0196713.
[26]
Leutner, M.; Matzhold, C.; Bellach, L.; Deischinger, C.; Harreiter, J.; Thurner, S.; Klimek, P.; Kautzky-Willer, A. Diagnosis of osteoporosis in statin-treated patients is dose-dependent. Ann. Rheum. Dis., 2019, 78(12), 1706-1711.
[http://dx.doi.org/10.1136/annrheumdis-2019-215714] [PMID: 31558481]
[27]
Blackman, A.L.; Pandit, N.S.; Pincus, K.J. Comparing rates of statin therapy in eligible patients living with HIV versus uninfected patients. HIV Med., 2020, 21(3), 135-141.
[http://dx.doi.org/10.1111/hiv.12794] [PMID: 31876122]
[28]
Jowkar, F.; Namazi, M.R. Statins in dermatology. Int. J. Dermatol., 2010, 49(11), 1235-1243.
[http://dx.doi.org/10.1111/j.1365-4632.2010.04579.x] [PMID: 20964647]
[29]
Kellesarian, S.; Al Amri, M.; Al-Kheraif, A.; Ghanem, A.; Malmstrom, H.; Javed, F. Efficacy of local and systemic statin delivery on the osseointegration of implants: A systematic Review. Int. J. Oral Maxillofac. Implants, 2017, 32(3), 497-506.
[http://dx.doi.org/10.11607/jomi.4955] [PMID: 28494034]
[30]
Dundar, S.; Bozoglan, A. Evaluation of the effects of topically applied simvastatin on titanium implant osseointegration. J. Oral Biol. Craniofac. Res., 2020, 10(2), 149-152.
[http://dx.doi.org/10.1016/j.jobcr.2020.04.004] [PMID: 32322477]
[31]
Atzmony, L.; Lim, Y.H.; Hamilton, C.; Leventhal, J.S.; Wagner, A.; Paller, A.S.; Choate, K.A. Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy. J. Am. Acad. Dermatol., 2020, 82(1), 123-131.
[http://dx.doi.org/10.1016/j.jaad.2019.08.043] [PMID: 31449901]
[32]
Auger, F.A.; Lacroix, D.; Germain, L. Skin substitutes and wound healing. Skin Pharmacol. Physiol., 2009, 22(2), 94-102.
[http://dx.doi.org/10.1159/000178868] [PMID: 19188757]
[33]
Bellosta, S.; Fed, N.; Bernini, F.; Paoletti, R.; Corsini, A. Non-lipid-related effects of statins. Ann. Med., 2000, 32(3), 164-176.
[http://dx.doi.org/10.3109/07853890008998823] [PMID: 10821323]
[34]
Williams, D.; Feely, J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin. Pharmacokinet., 2002, 41(5), 343-370.
[http://dx.doi.org/10.2165/00003088-200241050-00003] [PMID: 12036392]
[35]
Šimić, I.; Reiner, Z. Adverse effects of statins - myths and reality. Curr. Pharm. Des., 2015, 21(9), 1220-1226.
[http://dx.doi.org/10.2174/1381612820666141013134447] [PMID: 25312733]
[36]
Reiner, Ž. Resistance and intolerance to statins. Nutr. Metab. Cardiovasc. Dis., 2014, 24(10), 1057-1066.
[http://dx.doi.org/10.1016/j.numecd.2014.05.009] [PMID: 24996502]
[37]
Kaur, R.; Ajitha, M. Transdermal delivery of fluvastatin loaded nanoemulsion gel: Preparation, characterization and in vivo anti-osteoporosis activity. Eur. J. Pharm. Sci., 2019, 136, 104956.
[http://dx.doi.org/10.1016/j.ejps.2019.104956] [PMID: 31202895]
[38]
Prueksaritanont, T.; Gorham, L.M.; Ma, B.; Liu, L.; Yu, X.; Zhao, J.J.; Slaughter, D.E.; Arison, B.H.; Vyas, K.P. In vitro metabolism of simvastatin in humans [SBT]identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab. Dispos., 1997, 25(10), 1191-1199.
[PMID: 9321523]
[39]
Prueksaritanont, T.; Ma, B.; Yu, N. The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6. Br. J. Clin. Pharmacol., 2003, 56(1), 120-124.
[http://dx.doi.org/10.1046/j.1365-2125.2003.01833.x] [PMID: 12848784]
[40]
Backman, J.T.; Filppula, A.M.; Niemi, M.; Neuvonen, P.J. Role of cytochrome P450 2C8 in drug metabolism and interactions. Pharmacol. Rev., 2016, 68(1), 168-241.
[http://dx.doi.org/10.1124/pr.115.011411] [PMID: 26721703]
[41]
Liu, Y.; Zeng, B.H.; Shang, H.T.; Cen, Y.Y.; Wei, H. Bama miniature pigs (Sus scrofa domestica) as a model for drug evaluation for humans: Comparison of in vitro metabolism and in vivo pharmacokinetics of lovastatin. Comp. Med., 2008, 58(6), 580-587.
[PMID: 19149415]
[42]
Li, M.; Fan, L.Y.; Zhang, W.; Cao, C.X. Stacking and quantitative analysis of lovastatin in urine samples by the transient moving chemical reaction boundary method in capillary electrophoresis. Anal. Bioanal. Chem., 2007, 387(8), 2719-2725.
[http://dx.doi.org/10.1007/s00216-007-1169-3] [PMID: 17333149]
[43]
Liu, A.; Wu, Q.; Guo, J.; Ares, I.; Rodríguez, J.L.; Martínez-Larrañaga, M.R.; Yuan, Z.; Anadón, A.; Wang, X.; Martínez, M.A. Statins: Adverse reactions, oxidative stress and metabolic interactions. Pharmacol. Ther., 2019, 195, 54-84.
[http://dx.doi.org/10.1016/j.pharmthera.2018.10.004] [PMID: 30321555]
[44]
Sprecher, D.L.; Goodman, S.G.; Kannampuzha, P.; Pearce, G.L.; Langer, A. Skin tissue cholesterol (SkinTc) is related to angiographically-defined cardiovascular disease. Atherosclerosis, 2003, 171(2), 255-258.
[http://dx.doi.org/10.1016/S0021-9150(03)00290-9] [PMID: 14644394]
[45]
Babita, K.; Tiwary, A. Skin lipid synthesis inhibition: A possible means for enhancing percutaneous delivery of levodopa. Curr. Drug Deliv., 2004, 1(4), 397-403.
[http://dx.doi.org/10.2174/1567201043334579] [PMID: 16305401]
[46]
Brazzell, V.; Distante, F.; Perani, G.; Berardesca, E. Effects of systemic treatment with statins on skin barrier function and stratum corneum water-holding capacity. Dermatology, 1996, 192(3), 214-216.
[http://dx.doi.org/10.1159/000246368] [PMID: 8726633]
[47]
Dobs, A.S.; Levine, M.A.; Margolis, S. Effects of pravastatin, a new HMG-CoA reductase inhibitor, on vitamin D synthesis in man. Metabolism, 1991, 40(5), 524-528.
[http://dx.doi.org/10.1016/0026-0495(91)90235-O] [PMID: 1902546]
[48]
Albert, M.A.; Danielson, E.; Rifai, N.; Ridker, P.M. Effect of statin therapy on C-reactive protein levels: The pravastatin inflammation/CRP evaluation (PRINCE): A randomized trial and cohort study. JAMA, 2001, 286(1), 64-70.
[http://dx.doi.org/10.1001/jama.286.1.64] [PMID: 11434828]
[49]
Musial, J.; Undas, A.; Gajewski, P.; Jankowski, M.; Sydor, W.; Szczeklik, A. Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia. Int. J. Cardiol., 2001, 77(2-3), 247-253.
[http://dx.doi.org/10.1016/S0167-5273(00)00439-3] [PMID: 11182189]
[50]
Albert, M.A.; Glynn, R.J.; Ridker, P.M. Plasma concentration of C-reactive protein and the calculated framingham coronary heart disease risk score. Circulation, 2003, 108(2), 161-165.
[http://dx.doi.org/10.1161/01.CIR.0000080289.72166.CF] [PMID: 12835213]
[51]
Mowla, K.; Rajai, E.; Ghorbani, A.; Dargahi-Malamir, M.; Bahadoram, M.; Mohammadi, S. Effect of atorvastatin on the disease activity and severity of rheumatoid arthritis: Double-blind randomized controlled trial. J. Clin. Diagn. Res., 2016, 10(5), OC32-OC36.
[http://dx.doi.org/10.7860/JCDR/2016/16538.7814] [PMID: 27437268]
[52]
Nagashima, T.; Okazaki, H.; Yudoh, K.; Matsuno, H.; Minota, S. Apoptosis of rheumatoid synovial cells by statins through the blocking of protein geranylgeranylation: A potential therapeutic approach to rheumatoid arthritis. Arthritis Rheum., 2006, 54(2), 579-586.
[http://dx.doi.org/10.1002/art.21564] [PMID: 16447234]
[53]
Palinski, W.; Tsimikas, S. Immunomodulatory effects of statins: mechanisms and potential impact on arteriosclerosis. J. Am. Soc. Nephrol., 2002, 13(6), 1673-1681.
[http://dx.doi.org/10.1097/01.ASN.0000018400.39687.8C] [PMID: 12039998]
[54]
Kittleson, M.M.; Kobashigawa, J.A. Statins in heart transplantation. Clin. Transpl., 2013, 135-143.
[PMID: 25095502]
[55]
Chataway, J.; Schuerer, N.; Alsanousi, A.; Chan, D.; Mac-Manus, D.; Hunter, K.; Anderson, V.; Bangham, C.R.M.; Clegg, S.; Nielsen, C.; Fox, N.C.; Wilkie, D.; Nicholas, J.M.; Calder, V.L.; Greenwood, J.; Frost, C.; Nicholas, R. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): A randomised, placebo-controlled, phase 2 trial. Lancet, 2014, 383(9936), 2213-2221.
[http://dx.doi.org/10.1016/S0140-6736(13)62242-4] [PMID: 24655729]
[56]
Kamm, C.P.; El-Koussy, M.; Humpert, S.; Findling, O.; Bredow, F.; Burren, Y.; Schwegler, G.; Schött, D.; Donati, F.; Müller, M.; Goebels, N.; Müller, F.; Slotboom, J.; Tettenborn, B.; Kappos, L.; Naegelin, Y.; Mattle, H.P. Atorvastatin added to interferon β for relapsing multiple sclerosis: A randomized controlled trial. J. Neurol., 2012, 259(11), 2401-2413.
[http://dx.doi.org/10.1007/s00415-012-6513-7] [PMID: 22569835]
[57]
Rego, A.C.M.; Araújo Filho, I.; Damasceno, B.P.G.L.; Egito, E.S.T.; Silveira, I.A.; Brandão-Neto, J.; Medeiros, A.C. Simvastatin improves the healing of infected skin wounds of rats. Acta Cir. Bras., 2007, 22(Suppl. 1), 57-63.
[http://dx.doi.org/10.1590/S0102-86502007000700012] [PMID: 17505657]
[58]
Pruefer, D.; Makowski, J.; Schnell, M.; Buerke, U.; Dahm, M.; Oelert, H.; Sibelius, U.; Grandel, U.; Grimminger, F.; Seeger, W.; Meyer, J.; Darius, H.; Buerke, M. Simvastatin inhibits inflammatory properties of Staphylococcus aureus alpha-toxin. Circulation, 2002, 106(16), 2104-2110.
[http://dx.doi.org/10.1161/01.CIR.0000034048.38910.91] [PMID: 12379581]
[59]
Otuki, M.F.; Pietrovski, E.F.; Cabrini, D.A. Topical simvastatin: Preclinical evidence for a treatment of skin inflammatory conditions. J. Dermatol. Sci., 2006, 44(1), 45-47.
[http://dx.doi.org/10.1016/j.jdermsci.2006.04.006] [PMID: 16759838]
[60]
Jameel, A; Ooi, KG-J; Jeffs, NR; Galatowicz, G; Lightman, SL; Calder, VL Statin modulation of human T-cell proliferation, IL-1 and IL-17 production, and IFN-T cell expression: synergy with conventional immunosuppressive agents. Int. J. Inflamm., 2013, 2013
[61]
Stüve, O.; Youssef, S.; Slavin, A.J.; King, C.L.; Patarroyo, J.C.; Hirschberg, D.L.; Brickey, W.J.; Soos, J.M.; Piskurich, J.F.; Chapman, H.A.; Zamvil, S.S. The role of the MHC class II transactivator in class II expression and antigen presentation by astrocytes and in susceptibility to central nervous system autoimmune disease. J. Immunol., 2002, 169(12), 6720-6732.
[http://dx.doi.org/10.4049/jimmunol.169.12.6720] [PMID: 12471103]
[62]
Sobrin, L.; Yu, Y.; Han, S.; Susarla, G.; Kempen, J.H.; Hubbard, R.A.; VanderBeek, B.L. Decreased risk of non-infectious anterior uveitis with statin therapy in a large healthcare claims database. Graefes Arch. Clin. Exp. Ophthalmol., 2021, 259(9), 2783-2793.
[http://dx.doi.org/10.1007/s00417-021-05243-8] [PMID: 34050812]
[63]
Kim, Y.C.; Kim, K.K.; Shevach, E.M. Simvastatin induces Foxp3+ T regulatory cells by modulation of transforming growth factor-β signal transduction. Immunology, 2010, 130(4), 484-493.
[http://dx.doi.org/10.1111/j.1365-2567.2010.03269.x] [PMID: 20408897]
[64]
Namazi, M.R. Statins: novel additions to the dermatologic arsenal? Exp. Dermatol., 2004, 13(6), 337-339.
[http://dx.doi.org/10.1111/j.0906-6705.2004.00208.x] [PMID: 15186318]
[65]
Dellavalle, R.P.; Drake, A.; Graber, M.; Heilig, L.F.; Hester, E.J.; Johnson, K.R.; McNealy, K.; Schilling, L. Statins and fibrates for preventing melanoma. Cochrane Database Syst. Rev., 2005, (4), CD003697.
[PMID: 16235336]
[66]
Guasti, L.; Marino, F.; Cosentino, M.; Maio, R.C.; Rasini, E.; Ferrari, M.; Castiglioni, L.; Klersy, C.; Gaudio, G.; Grandi, A.M.; Lecchini, S.; Venco, A. Prolonged statin-associated reduction in neutrophil reactive oxygen species and angiotensin II type 1 receptor expression: 1-year follow-up. Eur. Heart J., 2008, 29(9), 1118-1126.
[http://dx.doi.org/10.1093/eurheartj/ehn138] [PMID: 18390537]
[67]
Goldstein, M.R.; Mascitelli, L.; Pezzetta, F. Statins, leptin and regulatory T cells. Nutr. Metab. Cardiovasc. Dis., 2008, 18(6), e27.
[http://dx.doi.org/10.1016/j.numecd.2008.01.001] [PMID: 18450434]
[68]
Lim, S.; Barter, P. Antioxidant effects of statins in the management of cardiometabolic disorders. J. Atheroscler. Thromb., 2014, 21(10), 997-1010.
[http://dx.doi.org/10.5551/jat.24398] [PMID: 25132378]
[69]
Sorrentino, S.; Landmesser, U. Nonlipid-lowering effects of statins. Curr. Treat. Options Cardiovasc. Med., 2005, 7(6), 459-466.
[http://dx.doi.org/10.1007/s11936-005-0031-1] [PMID: 16283973]
[70]
Ajith, T.A.; Riji, T.; Anu, V. In vitro anti-oxidant and DNA protective effects of the novel 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor rosuvastatin. Clin. Exp. Pharmacol. Physiol., 2008, 35(5-6), 625-629.
[http://dx.doi.org/10.1111/j.1440-1681.2007.04853.x] [PMID: 18177480]
[71]
Vincent, T.S.; Wülfert, E.; Merler, E. Inhibition of growth factor signaling pathways by lovastatin. Biochem. Biophys. Res. Commun., 1991, 180(3), 1284-1289.
[http://dx.doi.org/10.1016/S0006-291X(05)81334-8] [PMID: 1953779]
[72]
Louneva, N.; Huaman, G.; Fertala, J.; Jiménez, S.A. Inhibition of systemic sclerosis dermal fibroblast type I collagen production and gene expression by simvastatin. Arthritis Rheum., 2006, 54(4), 1298-1308.
[http://dx.doi.org/10.1002/art.21723] [PMID: 16575855]
[73]
Khoshneviszadeh, M.; Ashkani-Esfahani, S.; Namazi, M.R.; Noorafshan, A.; Geramizadeh, B.; Miri, R. Topical simvastatin enhances tissue regeneration in full-thickness skin wounds in rat models. Iran. J. Pharm. Res., 2014, 13(1), 263-269.
[PMID: 24734079]
[74]
Sawaya, A.P.; Pastar, I.; Stojadinovic, O.; Lazovic, S.; Davis, S.C.; Gil, J.; Kirsner, R.S.; Tomic-Canic, M. Topical mevastatin promotes wound healing by inhibiting the transcription factor c-Myc via the glucocorticoid receptor and the long non-coding RNA Gas5. J. Biol. Chem., 2018, 293(4), 1439-1449.
[http://dx.doi.org/10.1074/jbc.M117.811240] [PMID: 29158265]
[75]
Meyer-ter-Vehn, T.; Katzenberger, B.; Han, H.; Grehn, F.; Schlunck, G. Lovastatin inhibits TGF-β-induced myofibroblast transdifferentiation in human tenon fibroblasts. Invest. Ophthalmol. Vis. Sci., 2008, 49(9), 3955-3960.
[http://dx.doi.org/10.1167/iovs.07-1610] [PMID: 18421080]
[76]
Kamio, K.; Liu, X.D.; Sugiura, H.; Togo, S.; Kawasaki, S.; Wang, X.; Ahn, Y.; Hogaboam, C.; Rennard, S.I. Statins inhibit matrix metalloproteinase release from human lung fibroblasts. Eur. Respir. J., 2010, 35(3), 637-646.
[http://dx.doi.org/10.1183/09031936.00134707] [PMID: 19797126]
[77]
Oliver, M.F. Might treatment of hypercholesterolaemia increase non-cardiac mortality? Lancet, 1991, 337(8756), 1529-1531.
[http://dx.doi.org/10.1016/0140-6736(91)93208-Q] [PMID: 1675380]
[78]
Demierre, M.F.; Higgins, P.D.R.; Gruber, S.B.; Hawk, E.; Lippman, S.M. Statins and cancer prevention. Nat. Rev. Cancer, 2005, 5(12), 930-942.
[http://dx.doi.org/10.1038/nrc1751] [PMID: 16341084]
[79]
Edwards, P.A.; Ericsson, J. Sterols and isoprenoids: Signaling molecules derived from the cholesterol biosynthetic pathway. Annu. Rev. Biochem., 1999, 68(1), 157-185.
[http://dx.doi.org/10.1146/annurev.biochem.68.1.157] [PMID: 10872447]
[80]
Mo, H.; Elson, C.E. Studies of the isoprenoid-mediated inhibition of mevalonate synthesis applied to cancer chemotherapy and chemoprevention. Exp. Biol. Med. (Maywood), 2004, 229(7), 567-585.
[http://dx.doi.org/10.1177/153537020422900701] [PMID: 15229351]
[81]
Safwat, S.; Ishak, R.A.; Hathout, R.M.; Mortada, N.D. Statins anticancer targeted delivery systems: re-purposing an old molecule. J. Pharm. Pharmacol., 2017, 69(6), 613-624.
[http://dx.doi.org/10.1111/jphp.12707] [PMID: 28271498]
[82]
Bellosta, S.; Bernini, F.; Ferri, N.; Quarato, P.; Canavesi, M.; Arnaboldi, L.; Fumagalli, R.; Paoletti, R.; Corsini, A. Direct vascular effects of HMG-CoA reductase inhibitors. Atherosclerosis, 1998, 137(Suppl.), S101-S109.
[http://dx.doi.org/10.1016/S0021-9150(97)00319-5] [PMID: 9694549]
[83]
Chan, K.K.; Oza, A.M.; Siu, L.L. The statins as anticancer agents. Clin. Cancer Res., 2003, 9(1), 10-19.
[PMID: 12538446]
[84]
Wright, R.S.; Murphy, J.G.; Bybee, K.A.; Kopecky, S.L.; LaBlanche, J.M. Statin lipid-lowering therapy for acute myocardial infarction and unstable angina: Efficacy and mechanism of benefit. Mayo Clin. Proc., 2002, 77(10), 1085-1092.
[http://dx.doi.org/10.4065/77.10.1085] [PMID: 12374252]
[85]
Denoyelle, C.; Albanese, P.; Uzan, G.; Hong, L.; Vannier, J.P.; Soria, J.; Soria, C. Molecular mechanism of the anti-cancer activity of cerivastatin, an inhibitor of HMG-CoA reductase, on aggressive human breast cancer cells. Cell. Signal., 2003, 15(3), 327-338.
[http://dx.doi.org/10.1016/S0898-6568(02)00124-9] [PMID: 12531431]
[86]
Rao, S.; Porter, D.C.; Chen, X.; Herliczek, T.; Lowe, M.; Keyomarsi, K. Lovastatin-mediated G 1 arrest is through inhibition of the proteasome, independent of hydroxymethyl glutaryl-CoA reductase. Proc. Natl. Acad. Sci. USA, 1999, 96(14), 7797-7802.
[http://dx.doi.org/10.1073/pnas.96.14.7797] [PMID: 10393901]
[87]
Weitz-Schmidt, G.; Welzenbach, K.; Brinkmann, V.; Kamata, T.; Kallen, J.; Bruns, C.; Cottens, S.; Takada, Y.; Hommel, U. Statins selectively inhibit leukocyte function antigen-1 by binding to a novel regulatory integrin site. Nat. Med., 2001, 7(6), 687-692.
[http://dx.doi.org/10.1038/89058] [PMID: 11385505]
[88]
Pedersen, T.R.; Wilhelmsen, L.; Færgeman, O.; Strandberg, T.E.; Thorgeirsson, G.; Troedsson, L.; Kristianson, J.; Berg, K.; Cook, T.J.; Haghfelt, T.; Kjekshus, J.; Miettinen, T.; Olsson, A.G.; Pyörälä, K.; Wedel, H. Follow-up study of patients randomized in the scandinavian simvastatin survival study (4S) of cholesterol lowering. Am. J. Cardiol., 2000, 86(3), 257-262.
[http://dx.doi.org/10.1016/S0002-9149(00)00910-3] [PMID: 10922429]
[89]
Ghosh-Choudhury, N.; Mandal, C.C.; Ghosh-Choudhury, N.; Ghosh Choudhury, G. Simvastatin induces derepression of PTEN expression via NFκB to inhibit breast cancer cell growth. Cell. Signal., 2010, 22(5), 749-758.
[http://dx.doi.org/10.1016/j.cellsig.2009.12.010] [PMID: 20060890]
[90]
Katz, M.S. Therapy Insight: potential of statins for cancer chemoprevention and therapy. Nat. Clin. Pract. Oncol., 2005, 2(2), 82-89.
[http://dx.doi.org/10.1038/ncponc0097] [PMID: 16264880]
[91]
Ghasemi, A.; Ghashghai, Z.; Akbari, J.; Yazdani-Charati, J.; Salehifar, E.; Hosseinimehr, S.J. Topical atorvastatin 1% for prevention of skin toxicity in patients receiving radiation therapy for breast cancer: A randomized, double-blind, placebo-controlled trial. Eur. J. Clin. Pharmacol., 2019, 75(2), 171-178.
[http://dx.doi.org/10.1007/s00228-018-2570-x] [PMID: 30291370]
[92]
Capanema, N.S.V.; Carvalho, I.C.; Mansur, A.A.P.; Carvalho, S.M.; Lage, A.P.; Mansur, H.S. Hybrid hydrogel composed of carboxymethylcellulose–silver nanoparticles–doxorubicin for anticancer and antibacterial therapies against melanoma skin cancer cells. ACS Appl. Nano Mater., 2019, 2(11), 7393-7408.
[http://dx.doi.org/10.1021/acsanm.9b01924]
[93]
Akbarzadeh, I.; Keramati, M.; Azadi, A.; Afzali, E.; Shahbazi, R.; chiani, M.; Norouzian, D.; Bakhshandeh, H. Optimization, physicochemical characterization, and antimicrobial activity of a novel simvastatin nano-niosomal gel against E. coli and S. aureus. Chem. Phys. Lipids, 2021, 234, 105019.
[http://dx.doi.org/10.1016/j.chemphyslip.2020.105019] [PMID: 33232724]
[94]
Malta, R.; Loureiro, J.B.; Costa, P.; Sousa, E.; Pinto, M.; Saraiva, L.; Amaral, M.H. Development of lipid nanoparticles containing the xanthone LEM2 for topical treatment of melanoma. J. Drug Deliv. Sci. Technol., 2021, 61, 102226.
[http://dx.doi.org/10.1016/j.jddst.2020.102226]
[95]
Suterio, N.; Bazzo, G.C.; Rauber, G.S.; Silva, A.H.; Caon, T.; Parize, A.L.; Creczynski-Pasa, T.B.; Stulzer, H.K. Laponite® gel formulation containing simvastatin for melanoma treatment. Appl. Clay Sci., 2022, 228, 106651.
[http://dx.doi.org/10.1016/j.clay.2022.106651]
[96]
Llevadot, J.; Asahara, T. Efecto de las estatinas en la inducción de angiogénesis y vasculogénesis. Rev. Esp. Cardiol., 2002, 55(8), 838-844.
[http://dx.doi.org/10.1016/S0300-8932(02)76713-4] [PMID: 12199980]
[97]
Kureishi, Y.; Luo, Z.; Shiojima, I.; Bialik, A.; Fulton, D.; Lefer, D.J.; Sessa, W.C.; Walsh, K. The HMG-CoA reductase inhibitor simvastatin activates the protein kinase Akt and promotes angiogenesis in normocholesterolemic animals. Nat. Med., 2000, 6(9), 1004-1010.
[http://dx.doi.org/10.1038/79510] [PMID: 10973320]
[98]
Dimmeler, S.; Fleming, I.; Fisslthaler, B.; Hermann, C.; Busse, R.; Zeiher, A.M. Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature, 1999, 399(6736), 601-605.
[http://dx.doi.org/10.1038/21224] [PMID: 10376603]
[99]
Fulton, D.; Gratton, J.P.; McCabe, T.J.; Fontana, J.; Fujio, Y.; Walsh, K.; Franke, T.F.; Papapetropoulos, A.; Sessa, W.C. Regulation of endothelium-derived nitric oxide production by the protein kinase Akt. Nature, 1999, 399(6736), 597-601.
[http://dx.doi.org/10.1038/21218] [PMID: 10376602]
[100]
Vincent, L.; Chen, W.; Hong, L.; Mirshahi, F.; Mishal, Z.; Mirshahi-Khorassani, T.; Vannier, J.P.; Soria, J.; Soria, C. Inhibition of endothelial cell migration by cerivastatin, an HMG-CoA reductase inhibitor: Contribution to its anti-angiogenic effect. FEBS Lett., 2001, 495(3), 159-166.
[http://dx.doi.org/10.1016/S0014-5793(01)02337-7] [PMID: 11334884]
[101]
Urbich, C.; Dernbach, E.; Zeiher, A.M.; Dimmeler, S. Double-edged role of statins in angiogenesis signaling. Circ. Res., 2002, 90(6), 737-744.
[http://dx.doi.org/10.1161/01.RES.0000014081.30867.F8] [PMID: 11934843]
[102]
Asai, J.; Takenaka, H.; Hirakawa, S.; Sakabe, J.; Hagura, A.; Kishimoto, S.; Maruyama, K.; Kajiya, K.; Kinoshita, S.; Tokura, Y.; Katoh, N. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis. Am. J. Pathol., 2012, 181(6), 2217-2224.
[http://dx.doi.org/10.1016/j.ajpath.2012.08.023] [PMID: 23138019]
[103]
Farsaei, S.; Khalili, H.; Farboud, E.S. Potential role of statins on wound healing: review of the literature. Int. Wound J., 2012, 9(3), 238-247.
[http://dx.doi.org/10.1111/j.1742-481X.2011.00888.x] [PMID: 22050652]
[104]
Simko, F.; Matuskova, J.; Luptak, I.; Krajcirovicova, K.; Kucharska, J.; Gvozdjakova, A.; Babal, P.; Pechanova, O. Effect of simvastatin on remodeling of the left ventricle and aorta in L-NAME-induced hypertension. Life Sci., 2004, 74(10), 1211-1224.
[http://dx.doi.org/10.1016/j.lfs.2003.07.032] [PMID: 14697405]
[105]
Vukelic, S.; Stojadinovic, O.; Pastar, I.; Rabach, M.; Krzyzanowska, A.; Lebrun, E.; Davis, S.C.; Resnik, S.; Brem, H.; Tomic-Canic, M. Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. J. Biol. Chem., 2011, 286(12), 10265-10275.
[http://dx.doi.org/10.1074/jbc.M110.188268] [PMID: 21239489]
[106]
Pastar, I.; Stojadinovic, O.; Sawaya, A.P.; Stone, R.C.; Lindley, L.E.; Ojeh, N.; Vukelic, S.; Samuels, H.H.; Tomic-Canic, M. Skin metabolite, farnesyl pyrophosphate, regulates epidermal response to inflammation, oxidative stress, and migration. J. Cell. Physiol., 2016, 231(11), 2452-2463.
[http://dx.doi.org/10.1002/jcp.25357] [PMID: 26916741]
[107]
Lindley, L.E.; Stojadinovic, O.; Pastar, I.; Tomic-Canic, M. Biology and biomarkers for wound healing. Plast. Reconstr. Surg., 2016, 138(3)(Suppl.), 18S-28S.
[http://dx.doi.org/10.1097/PRS.0000000000002682] [PMID: 27556760]
[108]
Stojadinovic, O.; Pastar, I.; Nusbaum, A.G.; Vukelic, S.; Krzyzanowska, A.; Tomic-Canic, M. Deregulation of epidermal stem cell niche contributes to pathogenesis of nonhealing venous ulcers. Wound Repair Regen., 2014, 22(2), 220-227.
[http://dx.doi.org/10.1111/wrr.12142] [PMID: 24635172]
[109]
Toker, S.; Gulcan, E.; Çaycı, M.K.; Olgun, E.G.; Erbilen, E.; Özay, Y. Topical atorvastatin in the treatment of diabetic wounds. Am. J. Med. Sci., 2009, 338(3), 201-204.
[http://dx.doi.org/10.1097/MAJ.0b013e3181aaf209] [PMID: 19667969]
[110]
Erdogan, S. Liposomal nanocarriers for tumor imaging. J. Biomed. Nanotechnol., 2009, 5(2), 141-150.
[http://dx.doi.org/10.1166/jbn.2009.1016] [PMID: 20055092]
[111]
Prow, T.W.; Grice, J.E.; Lin, L.L.; Faye, R.; Butler, M.; Becker, W.; Wurm, E.M.T.; Yoong, C.; Robertson, T.A.; Soyer, H.P.; Roberts, M.S. Nanoparticles and microparticles for skin drug delivery. Adv. Drug Deliv. Rev., 2011, 63(6), 470-491.
[http://dx.doi.org/10.1016/j.addr.2011.01.012] [PMID: 21315122]
[112]
Schmalfuß, U.; Neubert, R.; Wohlrab, W. Modification of drug penetration into human skin using microemulsions. J. Control. Release, 1997, 46(3), 279-285.
[http://dx.doi.org/10.1016/S0168-3659(96)01609-4]
[113]
Jia, S; Xie, P; Hong, SJ; Galiano, RD; Mustoe, TA Local application of statins significantly reduced hypertrophic scarring in a rabbit ear model. Plast. Reconstr. Surg. Glob. Open, 2017, 5(6), e1294.
[http://dx.doi.org/10.1097/GOX.0000000000001294]
[114]
Xie, P.; Dolivo, D.M.; Jia, S.; Cheng, X.; Salcido, J.; Galiano, R.D.; Hong, S.J.; Mustoe, T.A. Liposome-encapsulated statins reduce hypertrophic scarring through topical application. Wound Repair Regen., 2020, 28(4), 460-469.
[http://dx.doi.org/10.1111/wrr.12811] [PMID: 32428986]
[115]
Yadav, M.; Schiavone, N.; Guzman-Aranguez, A.; Giansanti, F.; Papucci, L.; Perez de Lara, M.J.; Singh, M.; Kaur, I.P. Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD). Drug Deliv. Transl. Res., 2020, 10(4), 919-944.
[http://dx.doi.org/10.1007/s13346-020-00733-4] [PMID: 32270439]
[116]
Hao, Y.; Li, W.; Zhou, X.; Yang, F.; Qian, Z. Microneedles-based transdermal drug delivery systems: A review. J. Biomed. Nanotechnol., 2017, 13(12), 1581-1597.
[http://dx.doi.org/10.1166/jbn.2017.2474] [PMID: 29490749]
[117]
Marwah, H.; Garg, T.; Goyal, A.K.; Rath, G. Permeation enhancer strategies in transdermal drug delivery. Drug Deliv., 2016, 23(2), 564-578.
[http://dx.doi.org/10.3109/10717544.2014.935532] [PMID: 25006687]
[118]
Ranade, V.V.; Cannon, J.B. (2011). Drug Delivery Systems (3rd ed.). CRC Press.
[http://dx.doi.org/10.1201/b10846]
[119]
Korani, S.; Bahrami, S.; Korani, M.; Banach, M.; Johnston, T.P.; Sahebkar, A. Parenteral systems for statin delivery: A review. Lipids Health Dis., 2019, 18(1), 193.
[http://dx.doi.org/10.1186/s12944-019-1139-8] [PMID: 31690335]
[120]
Zhou, X.; Hao, Y.; Yuan, L.; Pradhan, S.; Shrestha, K.; Pradhan, O.; Liu, H.; Li, W. Nano-formulations for transdermal drug delivery: A review. Chin. Chem. Lett., 2018, 29(12), 1713-1724.
[http://dx.doi.org/10.1016/j.cclet.2018.10.037]
[121]
Lane, E. Transdermal delivery system for statin combination therapy; Google Patents, 2005.
[122]
Tiwari, R.; Pathak, K. Statins therapy: A review on conventional and novel formulation approaches. J. Pharm. Pharmacol., 2011, 63(8), 983-998.
[http://dx.doi.org/10.1111/j.2042-7158.2011.01273.x] [PMID: 21718281]
[123]
Zidan, A.S.; Hosny, K.M.; Ahmed, O.A.; Fahmy, U.A. Assessment of simvastatin niosomes for pediatric transdermal drug delivery. Drug Deliv., 2016, 23(5), 1536-1549.
[PMID: 25386740]
[124]
Xiang, N.; Zhou, X.; He, X.; Zhang, Y.; Zhang, J.; Zhang, Z.R.; Sun, X.; Gong, T.; Fu, Y. An injectable gel platform for the prolonged therapeutic effect of pitavastatin in the management of hyperlipidemia. J. Pharm. Sci., 2016, 105(3), 1148-1155.
[http://dx.doi.org/10.1016/j.xphs.2015.12.002] [PMID: 26886326]
[125]
Vasnawala, H.; Kavalipati, N.; Shah, J.; Ramakrishan, A. Pleiotropic effects of statins. Indian J. Endocrinol. Metab., 2015, 19(5), 554-562.
[http://dx.doi.org/10.4103/2230-8210.163106] [PMID: 26425463]
[126]
Liao, J.K.; Laufs, U. Pleiotropic effects of statins. Annu. Rev. Pharmacol. Toxicol., 2005, 45(1), 89-118.
[http://dx.doi.org/10.1146/annurev.pharmtox.45.120403.095748] [PMID: 15822172]
[127]
Davies, J.T.; Delfino, S.F.; Feinberg, C.E.; Johnson, M.F.; Nappi, V.L.; Olinger, J.T.; Schwab, A.P.; Swanson, H.I. Current and Emerging Uses of Statins in Clinical Therapeutics: A Review. Lipid Insights, 2016, 9, LPI.S37450.
[http://dx.doi.org/10.4137/LPI.S37450] [PMID: 27867302]
[128]
Eming, SA; Martin, P; Tomic-Canic, M Wound repair and regeneration: mechanisms, signaling, and translation. Sci. Transl. Med., 2014, 6(265), 265sr6.
[http://dx.doi.org/10.1126/scitranslmed.3009337]
[129]
Seto, H.; Ohba, H.; Tokunaga, K.; Hama, H.; Horibe, M.; Nagata, T. Topical administration of simvastatin recovers alveolar bone loss in rats. J. Periodontal Res., 2008, 43(3), 261-267.
[http://dx.doi.org/10.1111/j.1600-0765.2007.01024.x] [PMID: 18447852]
[130]
Moriyama, Y.; Ayukawa, Y.; Ogino, Y.; Atsuta, I.; Koyano, K. Topical application of statin affects bone healing around implants. Clin. Oral Implants Res., 2008, 19(6), 600-605.
[http://dx.doi.org/10.1111/j.1600-0501.2007.01508.x] [PMID: 18422989]
[131]
Mansour, G.; Al Ashwah, A.; Koura, A. Evaluation of simvastatin grafting around immediate dental implants in dogs. Implant Dent., 2014, 23(2), 195-199.
[http://dx.doi.org/10.1097/ID.0000000000000051] [PMID: 24637528]
[132]
Moriyama, Y.; Ayukawa, Y.; Ogino, Y.; Atsuta, I.; Todo, M.; Takao, Y.; Koyano, K. Local application of fluvastatin improves peri-implant bone quantity and mechanical properties: A rodent study. Acta Biomater., 2010, 6(4), 1610-1618.
[http://dx.doi.org/10.1016/j.actbio.2009.10.045] [PMID: 19887121]
[133]
Parihar, S.P.; Hartley, M.A.; Hurdayal, R.; Guler, R.; Brombacher, F. Topical simvastatin as host-directed therapy against severity of cutaneous leishmaniasis in mice. Sci. Rep., 2016, 6(1), 33458.
[http://dx.doi.org/10.1038/srep33458] [PMID: 27632901]
[134]
Thangamani, S.; Mohammad, H.; Abushahba, M.F.N.; Hamed, M.I.; Sobreira, T.J.P.; Hedrick, V.E.; Paul, L.N.; Seleem, M.N. Exploring simvastatin, an antihyperlipidemic drug, as a potential topical antibacterial agent. Sci. Rep., 2015, 5(1), 16407.
[http://dx.doi.org/10.1038/srep16407] [PMID: 26553420]
[135]
Castañeda, P.S.; Domínguez Delgado, C.L.; Cruz, I.M.R.; Contreras, L.M.M.; Trinidad, E.M.M.; Cervantes, M.L.; Escobar-Chávez, J.J. Development of poly (methyl vinyl ether-alt-maleic acid) microneedles for transdermal delivery of atorvastatin calcium. Curr. Pharm. Biotechnol., 2020, 21(9), 852-861.
[http://dx.doi.org/10.2174/1389201021666200217103302] [PMID: 32065098]
[136]
Anod, H.V.; Gupta, N.V.; Gowda, D.V.; M, M. Preparation and evaluation of simvastatin transdermal film. Int. J. Appl. Pharm., 2018, 10(5), 235.
[http://dx.doi.org/10.22159/ijap.2018v10i5.26657]
[137]
Shaker, D.S.; Ishak, R.A.H.; Elhuoni, M.A.; Ghoneim, A.M. Boosting transdermal delivery of atorvastatin calcium via o/w nanoemulsifying system: Two-step optimization, ex vivo and in vivo evaluation. Int. J. Pharm., 2020, 578, 119073.
[http://dx.doi.org/10.1016/j.ijpharm.2020.119073] [PMID: 31982556]
[138]
El Menshawe, S.F.; Nafady, M.M.; Aboud, H.M.; Kharshoum, R.M.; Elkelawy, A.M.M.H.; Hamad, D.S. Transdermal delivery of fluvastatin sodium via tailored spanlastic nanovesicles: mitigated Freund’s adjuvant-induced rheumatoid arthritis in rats through suppressing p38 MAPK signaling pathway. Drug Deliv., 2019, 26(1), 1140-1154.
[http://dx.doi.org/10.1080/10717544.2019.1686087] [PMID: 31736366]
[139]
Mahmoud, MO; Aboud, HM; Hassan, AH; Ali, AA; Johnston, TP Transdermal delivery of atorvastatin calcium from novel nanovesicular systems using polyethylene glycol fatty acid esters: Ameliorated effect without liver toxicity in poloxamer 407-induced hyperlipidemic rats. Journal of controlled release, 2017, 254, 10-22.
[140]
Gutierrez, GE; Lalka, D; Garrett, IR; Rossini, G; Mundy, GR Transdermal application of lovastatin to rats causes profound increases in bone formation and plasma concentrations. Osteoporos Int., 2006, 17(7), 1033-1042.
[http://dx.doi.org/10.1007/s00198-006-0079-0]
[141]
Madi, M.; Kassem, A. Topical simvastatin gel as a novel therapeutic modality for palatal donor site wound healing following free gingival graft procedure. Acta Odontol. Scand., 2018, 76(3), 212-219.
[http://dx.doi.org/10.1080/00016357.2017.1403648] [PMID: 29145771]
[142]
Ala, S.; Alvandipour, M.; Saeedi, M.; Hamidian, M.; Shiva, A.; Rahmani, N.; Faramarzi, F. Effects of topical atorvastatin (2%) on posthemorrhoidectomy pain and wound healing: A randomized double-blind placebo-controlled clinical trial. World J. Surg., 2017, 41(2), 596-602.
[http://dx.doi.org/10.1007/s00268-016-3749-x] [PMID: 27738832]
[143]
Farsaei, S.; Khalili, H.; Farboud, E.S.; Karimzadeh, I.; Beigmohammadi, M.T. Efficacy of topical atorvastatin for the treatment of pressure ulcers: A randomized clinical trial. Pharmacotherapy, 2014, 34(1), 19-27.
[http://dx.doi.org/10.1002/phar.1339] [PMID: 23940000]
[144]
Joshi, R; Olver, I; Keefe, D; Marafioti, T; Smith, K. A phase I study to assess the safety and activity of topical lovastatin (FP252S) for the prevention of chemotherapy-induced alopecia. Supportive Care Cancer, 2007, 15(9), 1109-1112.
[145]
Ahmadvand, A.; Yazdanfar, A.; Yasrebifar, F.; Mohammadi, Y.; Mahjub, R.; Mehrpooya, M. Evaluating the effects of oral and topical simvastatin in the treatment of acne vulgaris: A double-blind, randomized, placebo-controlled clinical trial. Curr. Clin. Pharmacol., 2019, 13(4), 279-283.
[http://dx.doi.org/10.2174/1574884713666180821143545] [PMID: 30129417]
[146]
Paudel, K.S.; Milewski, M.; Swadley, C.L.; Brogden, N.K.; Ghosh, P.; Stinchcomb, A.L. Challenges and opportunities in dermal/transdermal delivery. Ther. Deliv., 2010, 1(1), 109-131.
[http://dx.doi.org/10.4155/tde.10.16] [PMID: 21132122]
[147]
Barry, B.W. Novel mechanisms and devices to enable successful transdermal drug delivery. Eur. J. Pharm. Sci., 2001, 14(2), 101-114.
[http://dx.doi.org/10.1016/S0928-0987(01)00167-1] [PMID: 11500256]
[148]
Raza, K.; Singh, B.; Lohan, S.; Sharma, G.; Negi, P.; Yachha, Y.; Katare, O.P. Nano-lipoidal carriers of tretinoin with enhanced percutaneous absorption, photostability, biocompatibility and anti-psoriatic activity. Int. J. Pharm., 2013, 456(1), 65-72.
[http://dx.doi.org/10.1016/j.ijpharm.2013.08.019] [PMID: 23973754]
[149]
Raza, K.; Katare, O.P.; Setia, A.; Bhatia, A.; Singh, B. Improved therapeutic performance of dithranol against psoriasis employing systematically optimized nanoemulsomes. J. Microencapsul., 2013, 30(3), 225-236.
[http://dx.doi.org/10.3109/02652048.2012.717115] [PMID: 23088318]
[150]
Kurmi, B.D.; Tekchandani, P.; Paliwal, R.; Paliwal, S.R. Transdermal drug delivery: Opportunities and challenges for controlled delivery of therapeutic agents using nanocarriers. Curr. Drug Metab., 2017, 18(5), 481-495.
[http://dx.doi.org/10.2174/1389200218666170222150555] [PMID: 28228076]

Rights & Permissions Print Cite
Article Metrics
84
2
Wayfinder Image
Open Access Journals Promotions
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy