Transdermal Drug Delivery Systems and their Potential in Alzheimer’s Disease Management

Author(s): Panoraia I. Siafaka, Ece Ö. Bülbül, Gökce Mutlu, Mehmet E. Okur, Ioannis D. Karantas, Neslihan Ü. Okur*

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 19 , Issue 5 , 2020


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Alzheimer's disease is a neuropathological disease with symptoms such as language problems, confusion as to place or time, loss of interest in activities, which were previously enjoyed, behavioral changes, and memory loss. Alzheimer's disease and other types of dementia affect almost 46.8 million people globally and are estimated to strike about 131.5 million people in 2050. It has been reported that Alzheimer's is the sixth main cause of mortality. The most used drugs, which are currently approved by the Food, and Drug Administration for Alzheimer’s disease are donepezil, rivastigmine, galantamine, memantine, and the combination of donepezil and memantine. However, most of the drugs present various adverse effects. Recently, the transdermal drug delivery route has gained increasing attention as an emerging tool for Alzheimer's disease management. Besides, transdermal drug delivery systems seem to provide hope for the management of various diseases, due to the advantages that they offer in comparison with oral dosage forms. Herein, the current advancements in transdermal studies with potent features to achieve better Alzheimer's disease management are presented. Many researchers have shown that the transdermal systems provide higher efficiency since the first-pass hepatic metabolism effect can be avoided and a prolonged drug release rate can be achieved. In summary, the transdermal administration of Alzheimer's drugs is an interesting and promising topic, which should be further elaborated and studied.

Keywords: Transdermal, Alzheimer's disease, drug delivery systems, cholinesterase inhibitors, N-methyl-D-aspartate antagonists, neuropathological disease.

[1]
Dahm R. Alzheimer’s discovery. Curr Biol 2006; 16(21): R906-10.
[http://dx.doi.org/10.1016/j.cub.2006.09.056] [PMID: 17084683]
[2]
Cipriani G, Danti S, Carlesi C. Three men in a (same) boat: Alzheimer, Pick, Lewy. Historical Notes Eur Geriatr Med 2016; 7(6): 526-30.
[http://dx.doi.org/10.1016/j.eurger.2016.08.001]
[3]
Kochanek KD, Murphy SL, Xu J, Tejada-Vera B. Deaths: final data for 2014. Natl Vital Stat Rep 2016; 65(4): 1-122.
[PMID: 27378572]
[4]
Kolaj I, Imindu Liyanage S, Weaver DF. Phenylpropanoids and Alzheimer’s disease: a potential therapeutic platform. Neurochem Int 2018; 120: 99-111.
[5]
Prince M, Wimo A, Guerchet M, Gemma-Claire A, Wu Y-T, Prina M. World Alzheimer Report 2015: the global impact of dementia - an analysis of prevalence, incidence, cost and trends. Alzheimer’s Dis. Int 2015; p. 84.
[6]
Sahoo AK, Dandapat J, Dash UC, Kanhar S. Features and outcomes of drugs for combination therapy as multi-targets strategy to combat Alzheimer’s disease. J Ethnopharmacol 2018; 215: 42-73.
[http://dx.doi.org/10.1016/j.jep.2017.12.015] [PMID: 29248451]
[7]
Jiang XW, Lu HY, Xu Z, et al. In silico analyses for key genes and molecular genetic mechanism in epilepsy and Alzheimer’s disease. CNS Neurol Disord Drug Targets 2018; 17(8): 608-17.
[http://dx.doi.org/10.2174/1871527317666180724150839] [PMID: 30047339]
[8]
Gupta S, Singhal NK, Ganesh S, Sandhir R. Extending arms of insulin resistance from diabetes to Alzheimer’s disease: identification of potential therapeutic targets. CNS Neurol Disord Drug Targets 2019; 18(3): 172-84.
[http://dx.doi.org/10.2174/1871527317666181114163515] [PMID: 30430949]
[9]
Alzheimer’s Association. 2014 Alzheimer’s disease facts and figures. Alzheimers Dement 2014; 10(2): e47-92.
[http://dx.doi.org/10.1016/j.jalz.2014.02.001] [PMID: 24818261]
[10]
Takashima A. Mechanism of neurodegeneration through tau and therapy for Alzheimer’s disease. J Sport Health Sci 2016; 5(4): 391-2.
[11]
Song Y, Hu M, Zhang J, Teng ZQ, Chen C. A novel mechanism of synaptic and cognitive impairments mediated via microRNA-30b in Alzheimer’s disease. EBioMedicine 2019; 39: 409-21.
[http://dx.doi.org/10.1016/j.ebiom.2018.11.059] [PMID: 30522932]
[12]
Tan SH, Karri V, Tay NWR, et al. Emerging pathways to neurodegeneration: dissecting the critical molecular mechanisms in Alzheimer’s disease, Parkinson’s disease Biomed Pharmacother. Elsevier 2019; pp. 765-77.
[13]
Neelakandan AR, Rajanikant GK. Commentary: endophenotypes as disease modifiers: decoding the biology of Alzheimer’s by genome-wide association studies. CNS Neurol Disord Drug Targets 2018; 17(1): 6-8.
[http://dx.doi.org/10.2174/1871527317666180213143832] [PMID: 29437016]
[14]
Tejeswinee K, Shomona GJ, Athilakshmi R. Feature selection techniques for prediction of neuro-degenerative disorders: a case-study with Alzheimer’s and Parkinson’s disease. Procedia Comput Sci 2017; 115: 188-94.
[http://dx.doi.org/10.1016/j.procs.2017.09.125]
[15]
Gauthier S, Ng KP, Pascoal TA, Zhang H, Rosa-Neto P. Targeting Alzheimer’s disease at the right time and the right place: validation of a personalized approach to diagnosis and treatment. J Alzheimers Dis 2018; 64(s1): S23-31.
[http://dx.doi.org/10.3233/JAD-179924] [PMID: 29504543]
[16]
Karthivashan G, Ganesan P, Park SY, Kim JS, Choi DK. Therapeutic strategies and nano-drug delivery applications in management of ageing Alzheimer’s disease. Drug Deliv 2018; 25(1): 307-20.
[http://dx.doi.org/10.1080/10717544.2018.1428243] [PMID: 29350055]
[17]
Sgarbossa A, Giacomazza D, di Carlo M. Ferulic acid: a hope for Alzheimer’s disease therapy from plants. Nutrients 2015; 7(7): 5764-82.
[http://dx.doi.org/10.3390/nu7075246] [PMID: 26184304]
[18]
Ahmad SS, Khan S, Kamal MA, Wasi U. The structure and function of α, β and γ-secretase as therapeutic target enzymes in the development of Alzheimer’s disease: a review. CNS Neurol Disord Drug Targets 2019; 18(9): 657-67.
[http://dx.doi.org/10.2174/1871527318666191011145941] [PMID: 31608840]
[19]
Ibrahim MM, Gabr MT. Multitarget therapeutic strategies for Alzheimer’s disease. Neural Regen Res 2019; 14(3): 437-40.
[http://dx.doi.org/10.4103/1673-5374.245463] [PMID: 30539809]
[20]
Reeta, Baek SC, Lee JP, et al. Ethyl acetohydroxamate incorporated chalcones: unveiling a novel class of chalcones for multitarget monoamine oxidase-b inhibitors against Alzheimer’s disease. CNS Neurol Disord - Drug Targets 2019; 18(8): 643-54.
[21]
Sakurai R, Watanabe Y, Osuka Y, et al. Overlap between apolipoprotein eε4 allele and slowing gait results in cognitive impairment. Front Aging Neurosci 2019; 11: 247.
[http://dx.doi.org/10.3389/fnagi.2019.00247] [PMID: 31572165]
[22]
Aliev G, Ashraf GM, Tarasov VV, et al. Alzheimer’s disease – future therapy based on dendrimers 2018; 17: 288-94.
[23]
Sabbagh M, Cummings J. Progressive cholinergic decline in Alzheimer’s disease: consideration for treatment with donepezil 23 mg in patients with moderate to severe symptomatology. BMC Neurol 2011; 11: 21.
[http://dx.doi.org/10.1186/1471-2377-11-21] [PMID: 21299848]
[24]
Yavarpour-Bali H, Ghasemi-Kasman M, Shojaei A. Direct reprogramming of terminally differentiated cells into neurons: a novel and promising strategy for Alzheimer’s disease treatment. Prog Neuropsychopharmacol Biol Psychiatry 2020; 98: 109820.
[25]
Gordon BA, Blazey TM, Su Y, et al. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer’s disease: a longitudinal study. Lancet Neurol 2018; 17(3): 241-50.
[http://dx.doi.org/10.1016/S1474-4422(18)30028-0] [PMID: 29397305]
[26]
Hroudová J, Singh N, Fišar Z, Ghosh KK. Progress in drug development for Alzheimer’s disease: an overview in relation to mitochondrial energy metabolism. Eur J Med Chem 2016; 121: 774-84.
[http://dx.doi.org/10.1016/j.ejmech.2016.03.084] [PMID: 27094132]
[27]
Swerdlow R, Burns J, Khan SM. The AD mitochondrial cascade hypothesis. J Alzheimers Dis 2010; 20(Suppl. 2): 265-79.
[http://dx.doi.org/10.3233/JAD-2010-100339]
[28]
Markesbery WR. Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 1997; 23(1): 134-47.
[http://dx.doi.org/10.1016/S0891-5849(96)00629-6] [PMID: 9165306]
[29]
Praticò D. Oxidative stress hypothesis in Alzheimer’s disease: a reappraisal. Trends Pharmacol Sci 2008; 29(12): 609-15.
[http://dx.doi.org/10.1016/j.tips.2008.09.001] [PMID: 18838179]
[30]
Eikelenboom P. The inflammatory hypothesis of Alzheimer’s disease: where do we stand? Eur Neuropsychopharmacol 2002; 12: 98-9.
[http://dx.doi.org/10.1016/S0924-977X(02)80031-1]
[31]
Zotova E, Nicoll JA, Kalaria R, Holmes C, Boche D. Inflammation in Alzheimer’s disease: relevance to pathogenesis and therapy. Alzheimers Res Ther 2010; 2(1): 1-9.
[http://dx.doi.org/10.1186/alzrt24] [PMID: 20122289]
[32]
Morgan AR, Touchard S, Leckey C, et al. NIMA Consortium; Annex: NIMA–Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer’s Disease. Inflammatory biomarkers in Alzheimer’s disease plasma. Alzheimers Dement 2019; 15(6): 776-87.
[http://dx.doi.org/10.1016/j.jalz.2019.03.007] [PMID: 31047856]
[33]
Chakravarty A. Unifying concept for Alzheimer’s disease, vascular dementia and normal pressure hydrocephalus - a hypothesis. Med Hypotheses 2004; 63(5): 827-33.
[http://dx.doi.org/10.1016/j.mehy.2004.03.029] [PMID: 15488655]
[34]
de la Torre JC. The vascular hypothesis of Alzheimer’s disease: bench to bedside and beyond. Neurodegener Dis 2010; 7(1-3): 116-21.
[http://dx.doi.org/10.1159/000285520] [PMID: 20173340]
[35]
Mathew A, Yoshida Y, Maekawa T, Sakthi Kumar D. Alzheimer’s disease: cholesterol a menace? Brain Research Bulletin 2011; 86(1-2): 1-12.
[36]
Wood WG, Li L, Müller WE, Eckert GP. Cholesterol as a causative factor in Alzheimer’s disease: a debatable hypothesis. J Neurochem 2014; 129(4): 559-72.
[http://dx.doi.org/10.1111/jnc.12637] [PMID: 24329875]
[37]
Loera-Valencia R, Goikolea J, Parrado-Fernandez C, Merino-Serrais P, Maioli S. Alterations in cholesterol metabolism as a risk factor for developing Alzheimer’s disease: potential novel targets for treatment. J Steroid Biochem Mol Biol 2019; 190: 104-14.
[http://dx.doi.org/10.1016/j.jsbmb.2019.03.003] [PMID: 30878503]
[38]
Armstrong RA, Winsper SJ, Blair JA. Hypothesis: is Alzheimer’s disease a metal-induced immune disorder? Neurodegeneration 1995; 4(1): 107-11.
[http://dx.doi.org/10.1006/neur.1995.0013] [PMID: 7600179]
[39]
Bush AI, Tanzi RE. Therapeutics for Alzheimer’s disease based on the metal hypothesis. Neurotherapeutics 2008; 5(3): 421-32.
[http://dx.doi.org/10.1016/j.nurt.2008.05.001] [PMID: 18625454]
[40]
Tiiman A, Palumaa P, Tõugu V. The missing link in the amyloid cascade of Alzheimer’s disease - metal ions. Neurochem Int 2013; 62(4): 367-78.
[http://dx.doi.org/10.1016/j.neuint.2013.01.023] [PMID: 23395747]
[41]
Koseoglu E, Koseoglu R, Kendirci M, Saraymen R, Saraymen B. Trace metal concentrations in hair and nails from Alzheimer’s disease patients: relations with clinical severity. J Trace Elem Med Biol 2017; 39: 124-8.
[http://dx.doi.org/10.1016/j.jtemb.2016.09.002] [PMID: 27908403]
[42]
Neve RL, McPhie DL. The cell cycle as a therapeutic target for Alzheimer’s disease. Pharmacol Ther 2006; 111(1): 99-113.
[http://dx.doi.org/10.1016/j.pharmthera.2005.09.005] [PMID: 16274748]
[43]
Woods J, Snape M, Smith MA. The cell cycle hypothesis of Alzheimer’s disease: suggestions for drug development. Biochim Biophys Acta 2007; 1772(4): 503-8.
[http://dx.doi.org/10.1016/j.bbadis.2006.12.004] [PMID: 17223322]
[44]
Girek M, Szymański P. Tacrine hybrids as multi-target-directed ligands in Alzheimer’s disease: influence of chemical structures on biological activities. Chem Pap 2019; 73(2): 269-89.
[http://dx.doi.org/10.1007/s11696-018-0590-8]
[45]
FDA-Approved Treatments for Alzheimer’s. Alzheimer’s Assoc 2019; 1-5.
[46]
Bhattacharjee S, Patanwala AE, Lo-Ciganic WH, et al. Alzheimer’s disease medication and risk of all-cause mortality and all-cause hospitalization: a retrospective cohort study. Alzheimers Dement (N Y) 2019; 5: 294-302.
[http://dx.doi.org/10.1016/j.trci.2019.05.005] [PMID: 31338414]
[47]
Korábečný J, Nepovimová E, Cikánková T, et al. Newly developed drugs for Alzheimer’s disease in relation to energy metabolism, cholinergic and monoaminergic neurotransmission. Neuroscience 2018; 370: 191-206.
[http://dx.doi.org/10.1016/j.neuroscience.2017.06.034] [PMID: 28673719]
[48]
Agatonovic-Kustrin S, Kettle C, Morton DW. A molecular approach in drug development for Alzheimer’s disease. Biomed Pharmacother 2018; 106: 553-65.
[http://dx.doi.org/10.1016/j.biopha.2018.06.147] [PMID: 29990843]
[49]
Giacomeli R, Izoton JC, Dos Santos RB, Boeira SP, Jesse CR, Haas SE. Neuroprotective effects of curcumin lipid-core nanocapsules in a model Alzheimer’s disease induced by β-amyloid 1-42 peptide in aged female mice. Brain Res 2019; 1721: 146325.
[http://dx.doi.org/10.1016/j.brainres.2019.146325] [PMID: 31325424]
[50]
Chen H, Liu S, Ji L, et al. Folic acid supplementation mitigates Alzheimer’s disease by reducing inflammation: a randomized controlled trial. Mediators Inflamm 2016; 2016: 5912146.
[http://dx.doi.org/10.1155/2016/5912146]
[51]
Reddy PH. Mitochondrial oxidative damage in aging and Alzheimer’s disease: implications for mitochondrially targeted antioxidant therapeutics. J Biomed Biotechnol 2006; 2006(3): 31372.
[http://dx.doi.org/10.1155/JBB/2006/31372] [PMID: 17047303]
[52]
Lv H, Liu Q, Zhou J, Tan G, Deng X, Ci X. Daphnetin-mediated Nrf2 antioxidant signaling pathways ameliorate tert-butyl hydroperoxide (t-BHP)-induced mitochondrial dysfunction and cell death. Free Radic Biol Med 2017; 106: 38-52.
[http://dx.doi.org/10.1016/j.freeradbiomed.2017.02.016] [PMID: 28188924]
[53]
Xing S, Zhu C, Zhang R, An L. Huperzine A in the treatment of Alzheimer’s disease and vascular dementia: a meta-analysis. Evid Based Complement Alternat Med 2014; 2014: 363985.
[54]
Chaiyana W, Saeio K, Hennink WE, Okonogi S. Characterization of potent anticholinesterase plant oil based microemulsion. Int J Pharm 2010; 401(1-2): 32-40.
[http://dx.doi.org/10.1016/j.ijpharm.2010.09.005] [PMID: 20837121]
[55]
Ali F, Siddique YH. Bioavailability and pharmaco-therapeutic potential of luteolin in overcoming Alzheimer’s disease. CNS Neurol Disord Drug Targets 2019; 18(5): 352-65.
[http://dx.doi.org/10.2174/1871527318666190319141835] [PMID: 30892166]
[56]
Singh A, Hasan A, Tiwari S, Pandey LM. Therapeutic advancement in Alzheimer disease: new hopes on the horizon? CNS Neurol Disord Drug Targets 2018; 17(8): 571-89.
[http://dx.doi.org/10.2174/1871527317666180627122448] [PMID: 29952273]
[57]
Siafaka PI, Okur ME, Ayla Ş, Er S, Cağlar EŞ, Okur NÜ. Design and characterization of nanocarriers loaded with levofloxacin for enhanced antimicrobial activity; physicochemical properties, in vitro release and oral acute toxicity. Braz J Pharm Sci 2019; 55: 1-13.
[http://dx.doi.org/10.1590/s2175-97902019000118295]
[58]
Okur ME, Karantas ID, Şenyiğit Z, Üstündağ Okur N, Siafaka PI. Recent trends on wound management; new therapeutic choices based on polymeric carriers. Asian J Pharm Sci 2020. [Epub ahead of print.]
[59]
Siafaka PI, Zisi AP, Exindari MK, Karantas ID, Bikiaris DN. Porous dressings of modified chitosan with poly(2-hydroxyethyl acrylate) for topical wound delivery of levofloxacin. Carbohydr Polym 2016; 143: 90-9.
[http://dx.doi.org/10.1016/j.carbpol.2016.02.009] [PMID: 27083347]
[60]
Üstündağ Okur N, Filippousi M, Okur ME, et al. A novel approach for skin infections: controlled release topical mats of poly(lactic acid)/poly(ethylene succinate) blends containing Voriconazole. J Drug Deliv Sci Technol 2018; 46: 74-86.
[http://dx.doi.org/10.1016/j.jddst.2018.05.005]
[61]
Perumal O, Murthy SN, Kalia YN. Turning theory into practice: the development of modern transdermal drug delivery systems and future trends. Skin Pharmacol Physiol 2013; 26(4-6): 331-42.
[http://dx.doi.org/10.1159/000351815] [PMID: 23921120]
[62]
Kearney MC, Caffarel-Salvador E, Fallows SJ, McCarthy HO, Donnelly RF. Microneedle-mediated delivery of donepezil: potential for improved treatment options in Alzheimer’s disease. Eur J Pharm Biopharm 2016; 103: 43-50.
[http://dx.doi.org/10.1016/j.ejpb.2016.03.026] [PMID: 27018330]
[63]
Siafaka PI, Barmbalexis P, Bikiaris DN. Novel electrospun nanofibrous matrices prepared from poly(lactic acid)/poly(butylene adipate) blends for controlled release formulations of an anti-rheumatoid agent. Eur J Pharm Sci 2016; 88: 12-25.
[http://dx.doi.org/10.1016/j.ejps.2016.03.021] [PMID: 27039136]
[64]
Alkilani AZ, McCrudden MTC, Donnelly RF. Transdermal drug delivery: innovative pharmaceutical developments based on disruption of the barrier properties of the stratum corneum. Pharmaceutics 2015; 7(4): 438-70.
[http://dx.doi.org/10.3390/pharmaceutics7040438] [PMID: 26506371]
[65]
Schoellhammer CM, Blankschtein D, Langer R. Skin permeabilization for transdermal drug delivery: recent advances and future prospects. Expert Opin Drug Deliv 2014; 11(3): 393-407.
[http://dx.doi.org/10.1517/17425247.2014.875528] [PMID: 24392787]
[66]
Leppert W, Malec-Milewska M, Zajaczkowska R, Wordliczek J. Transdermal and topical drug administration in the treatment of pain. Molecules 2018; 23(3): 681.
[http://dx.doi.org/10.3390/molecules23030681] [PMID: 29562618]
[67]
Frölich L. A review of the first transdermal treatment for Alzheimer’s disease - the rivastigmine patch. Eur Neurol Rev 2008; 3(1): 20.
[http://dx.doi.org/10.17925/ENR.2008.03.01.20]
[68]
Reñé R, Ricart J, Hernández B. From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease. Neurol 2014; 29(2): 86-93.
[69]
Waghule T, Singhvi G, Dubey SK, et al. Microneedles: a smart approach and increasing potential for transdermal drug delivery system. Biomed Pharmacother 2019; 109(109): 1249-58.
[http://dx.doi.org/10.1016/j.biopha.2018.10.078] [PMID: 30551375]
[70]
Szumała P, Jungnickel C, Kozłowska-Tylingo K, Jacyna B, Cal K. Transdermal transport of collagen and hyaluronic acid using water in oil microemulsion. Int J Pharm 2019; 572(July): 118738.
[http://dx.doi.org/10.1016/j.ijpharm.2019.118738] [PMID: 31705977]
[71]
Galipoğlu M, Erdal MS, Güngör S. Biopolymer-based transdermal films of donepezil as an alternative delivery approach in Alzheimer’s disease treatment. AAPS PharmSciTech 2015; 16(2): 284-92.
[http://dx.doi.org/10.1208/s12249-014-0224-6] [PMID: 25273029]
[72]
Shi J, Cong W, Wang Y, Liu Q, Luo G. Microemulsion-based patch for transdermal delivery of huperzine A and ligustrazine phosphate in treatment of Alzheimer’s disease. Drug Dev Ind Pharm 2012; 38(6): 752-61.
[http://dx.doi.org/10.3109/03639045.2011.625031] [PMID: 22014311]
[73]
Tanwar H, Sachdeva R. Transdermal drug delivery systems: a review. Int J Pharm Sci Res 2013; 3: 2274-90.
[74]
Ng LC, Gupta M. Transdermal drug delivery systems in diabetes management: a review. Asian J Pharm Sci 2020; 15(1): 13-25.
[75]
Bruschi ML. Drug delivery systems strategies to modify the drug release from pharmaceutical systems 2015. 87-194.
[76]
Haque T, Talukder MMU. Chemical enhancer: a simplistic way to modulate barrier function of the stratum corneum. Adv Pharm Bull 2018; 8(2): 169-79.
[http://dx.doi.org/10.15171/apb.2018.021] [PMID: 30023318]
[77]
Rehman K, Zulfakar MH. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm 2014; 40(4): 433-40.
[http://dx.doi.org/10.3109/03639045.2013.828219] [PMID: 23937582]
[78]
Abdulbaqi IM, Darwis Y, Assi RA, Khan NAK. Transethosomal gels as carriers for the transdermal delivery of colchicine: statistical optimization, characterization, and ex vivo evaluation. Drug Des Devel Ther 2018; 12: 795-813.
[http://dx.doi.org/10.2147/DDDT.S158018] [PMID: 29670336]
[79]
Lu GW, Gao P. Emulsions and Microemulsions for Topical and Transdermal Drug Delivery Handbook of Non-Invasive Drug Delivery Systems. Amsterdam: Elsevier 2010; pp. 59-94.
[http://dx.doi.org/10.1016/B978-0-8155-2025-2.10003-4]
[80]
Prausnitz MR, Langer R. Transdermal drug delivery. Nat Biotechnol 2008; 26(11): 1261-8.
[http://dx.doi.org/10.1038/nbt.1504] [PMID: 18997767]
[81]
Nandagopal MSG, Antony R, Rangabhashiyam S, Sreekumar N, Selvaraju N. Overview of microneedle system: a third generation transdermal drug delivery approach. Microsyst Technol 2014; 20: 1249-72.
[http://dx.doi.org/10.1007/s00542-014-2233-5]
[82]
Kathe K, Kathpalia H. Film forming systems for topical and transdermal drug delivery. Asian J Pharm Sci 2017; 12(6): 487-97.
[http://dx.doi.org/10.1016/j.ajps.2017.07.004] [PMID: 32104362]
[83]
Zeeshan M, Mukhtar M, Ul Ain Q, Khan S, Ali H. Nanopharmaceuticals: a boon to the brain-targeted drug delivery. Pharmaceutical Formulation Design - Recent Practices 2020.
[http://dx.doi.org/10.5772/intechopen.83040]
[84]
Chalbot S, Zetterberg H, Blennow K, et al. Blood-cerebrospinal fluid barrier permeability in Alzheimer’s disease. J Alzheimers Dis 2011; 25(3): 505-15.
[http://dx.doi.org/10.3233/JAD-2011-101959] [PMID: 21471645]
[85]
Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol 2015; 7(1): a020412.
[http://dx.doi.org/10.1101/cshperspect.a020412] [PMID: 25561720]
[86]
Banks WA. From blood-brain barrier to blood-brain interface: new opportunities for CNS drug delivery. Nat Rev Drug Discov 2016; 15(4): 275-92.
[http://dx.doi.org/10.1038/nrd.2015.21] [PMID: 26794270]
[87]
Dong X. Current strategies for brain drug delivery. Theranostics 2018; 8(6): 1481-93.
[http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
[88]
Farlow M R, Somogyi M. Transdermal patches for the treatment of neurologic conditions in elderly patients: a review. Prim Care Companion CNS Disord 2011; 13(6): PCC.11r01149.
[http://dx.doi.org/10.4088/PCC.11r01149]
[89]
Lu C-T, Zhao Y-Z, Wong HL, Cai J, Peng L, Tian X-Q. Current approaches to enhance CNS delivery of drugs across the brain barriers. Int J Nanomedicine 2014; 9: 2241-57.
[http://dx.doi.org/10.2147/IJN.S61288] [PMID: 24872687]
[90]
Lehrer S, Rheinstein PH. Transspinal delivery of drugs by transdermal patch back-of-neck for Alzheimer’s disease: a new route of administration. Discov Med 2019; 27(146): 37-43.
[PMID: 30721650]
[91]
Alexander A, Agrawal M, Uddin A, et al. Recent expansions of novel strategies towards the drug targeting into the brain. Int J Nanomedicine 2019; 14: 5895-909.
[http://dx.doi.org/10.2147/IJN.S210876] [PMID: 31440051]
[92]
Agrawal L, Vimal SK, Chen M-H, Shiga T. An idea of using microneedles for the targeted drug delivery to overcome the blood brain barrier for the treatment of brain diseases. J Pharmacovigil 2018; 6(5): 1-4.
[http://dx.doi.org/10.4172/2329-6887.1000270]
[93]
Altinoglu G, Adali T. Alzheimer’s disease targeted nano-based drug delivery systems. Curr Drug Targets 2020; 21(7): 628-46.
[http://dx.doi.org/10.2174/1389450120666191118123151] [PMID: 31744447]
[94]
Wong KH, Riaz MK, Xie Y, et al. Review of current strategies for delivering Alzheimer’s disease drugs across the blood-brain barrier. Int J Mol Sci 2019; 20(2): 381.
[http://dx.doi.org/10.3390/ijms20020381] [PMID: 30658419]
[95]
Scheindlin S. Transdermal drug delivery: past, present, future. Mol Interv 2004; 4(6): 308-12.
[http://dx.doi.org/10.1124/mi.4.6.1] [PMID: 15616157]
[96]
Wokovich AM, Prodduturi S, Doub WH, Hussain AS, Buhse LF. Transdermal Drug Delivery System (TDDS) adhesion as a critical safety, efficacy and quality attribute. Eur J Pharm Biopharm 2006; 64(1): 1-8.
[http://dx.doi.org/10.1016/j.ejpb.2006.03.009] [PMID: 16797171]
[97]
Woo FY, Basri M, Masoumi HRF, Ahmad MB, Ismail M. Formulation optimization of galantamine hydrobromide loaded gel drug reservoirs in transdermal patch for Alzheimer’s disease. Int J Nanomedicine 2015; 10: 3879-86.
[http://dx.doi.org/10.2147/IJN.S80253] [PMID: 26089664]
[98]
Blesa González R, Boada Rovira M, Martínez Parra C, Gil-Saladié D, Almagro CA, Gobartt Vázquez AL. Evaluation of the convenience of changing the rivastigmine administration route in patients with Alzheimer disease. Neurol 2011; 26(5): 262-71.
[http://dx.doi.org/10.1016/S2173-5808(11)70057-8]
[99]
Değirmenci Y, Keçeci H. Visual hallucinations due to rivastigmine transdermal patch application in Alzheimer’s disease; the first case report. Int J Gerontol 2016; 10(4): 240-1.
[http://dx.doi.org/10.1016/j.ijge.2015.10.010]
[100]
Kim H, Han HJ. The effect of rivastigmine transdermal patch on sleep apnea in patients with probable Alzheimer’s disease. Dement Neurocognitive Disord 2016; 15(4): 153-8.
[http://dx.doi.org/10.12779/dnd.2016.15.4.153] [PMID: 30906358]
[101]
Zhang ZX, Hong Z, Wang YP, et al. Rivastigmine patch in Chinese patients with probable Alzheimer’s disease: a 24-week, randomized, double-blind parallel-group study comparing rivastigmine patch (9.5 mg/24 h) with capsule (6 mg twice daily). CNS Neurosci Ther 2016; 22(6): 488-96.
[http://dx.doi.org/10.1111/cns.12521] [PMID: 27012596]
[102]
Adler G, Mueller B, Articus K. The transdermal formulation of rivastigmine improves caregiver burden and treatment adherence of patients with Alzheimer’s disease under daily practice conditions. Int J Clin Pract 2014; 68(4): 465-70.
[http://dx.doi.org/10.1111/ijcp.12374] [PMID: 24588972]
[103]
Farlow MR, Grossberg GT, Sadowsky CH, Meng X, Velting DMA. A 24-week, open-label extension study to investigate the long-term safety, tolerability, and efficacy of 13.3 mg/24 h rivastigmine patch in patients with severe Alzheimer disease. Alzheimer Dis Assoc Disord 2015; 29(2): 110-6.
[PMID: 25437301]
[104]
Tezel G, Timur SS, Bozkurt İ, et al. A snapshot on the current status of Alzheimer’s disease, treatment perspectives, in vitro and in vivo research studies and future opportunities. Chem Pharm Bull (Tokyo) 2019; 67(10): 1030-41.
[http://dx.doi.org/10.1248/cpb.c19-00511] [PMID: 31341111]
[105]
Atri A. the alzheimer’s disease clinical spectrum: diagnosis and management. Med Clin North Am 2019; 103(2): 263-93.
[106]
Fong Yen W, Basri M, Ahmad M, Ismail M. Formulation and evaluation of galantamine gel as drug reservoir in transdermal patch delivery system. ScientificWorldJournal 2015; 2015: 495271.
[http://dx.doi.org/10.1155/2015/495271] [PMID: 25853145]
[107]
Ameen D, Michniak-Kohn B. Development and in vitro evaluation of pressure sensitive adhesive patch for the transdermal delivery of galantamine: effect of penetration enhancers and crystallization inhibition. Eur J Pharm Biopharm 2019; 139: 262-71.
[http://dx.doi.org/10.1016/j.ejpb.2019.04.008] [PMID: 30981946]
[108]
Park CW, Son DD, Kim JY, et al. Investigation of formulation factors affecting in vitro and in vivo characteristics of a galantamine transdermal system. Int J Pharm 2012; 436(1-2): 32-40.
[http://dx.doi.org/10.1016/j.ijpharm.2012.06.057] [PMID: 22771734]
[109]
Yoon SK, Bae K-S, Hong D, et al. Pharmacokinetic and pharmacodynamic modeling and simulation analysis of icure donepezil patch in healthy male volunteers. Clin Ther 2017; 39(8): e55.
[http://dx.doi.org/10.1016/j.clinthera.2017.05.171]
[110]
Kodoth AK, Ghate VM, Lewis SA, Prakash B, Badalamoole V. Pectin-based silver nanocomposite film for transdermal delivery of Donepezil. Int J Biol Macromol 2019; 134: 269-79.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.04.191] [PMID: 31047929]
[111]
Madan RJS, Argade N, Dua K. Formulation and evaluation of transdermal patches of donepezil. Recent Pat Drug Deliv Formul 2015; 9(1): 95-103.
[PMID: 25354347]
[112]
Saluja S, Kasha PC, Paturi J, Anderson C, Morris R, Banga AK. A novel electronic skin patch for delivery and pharmacokinetic evaluation of donepezil following transdermal iontophoresis. Int J Pharm 2013; 453(2): 395-9.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.029] [PMID: 23735902]
[113]
del Rio-Sancho S, Serna-Jiménez CE, Calatayud-Pascual MA, et al. Transdermal absorption of memantin--effect of chemical enhancers, iontophoresis, and role of enhancer lipophilicity. Eur J Pharm Biopharm 2012; 82(1): 164-70.
[http://dx.doi.org/10.1016/j.ejpb.2012.06.005] [PMID: 22732268]
[114]
Del Río-Sancho S, Serna-Jiménez CE, Sebastián-Morelló M, et al. Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport. Int J Pharm 2017; 517(1-2): 104-11.
[http://dx.doi.org/10.1016/j.ijpharm.2016.11.038] [PMID: 27865983]
[115]
Otto A, du Plessis J. The Effects of Emulsifiers and Emulsion Formulation Types on Dermal and Transdermal Drug Delivery Percutaneous Penetration Enhancers Chemical Methods in Penetration Enhancement. Berlin, Heidelberg: Springer Berlin Heidelberg 2015; pp. 223-41.
[116]
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Adv Drug Deliv Rev 2012; 64(Suppl.): 175-93.
[http://dx.doi.org/10.1016/j.addr.2012.09.018] [PMID: 11104900]
[117]
Üstündağ Okur N, Çağlar EŞ, Siafaka PI. Novel ocular drug delivery systems: an update on microemulsions. J Ocul Pharmacol Ther 2020; 36(6)
[118]
Okur NÜ, Er S, Çağlar EŞ, Ekmen TZ, Sala F. Formulation of microemulsions for dermal delivery of cephalexin. ACTA Pharm Sci 2017; 55(4): 27.
[http://dx.doi.org/10.23893/1307-2080.APS.05524]
[119]
Fanun M. Microemulsions as delivery systems. Curr Opin Colloid Interface Sci 2012; 17(5): 306-13.
[http://dx.doi.org/10.1016/j.cocis.2012.06.001]
[120]
Nastiti CMRR, Ponto T, Abd E, Grice JE, Benson HAE, Roberts MS. Topical nano and microemulsions for skin delivery. Pharmaceutics 2017; 9(4): 37.
[http://dx.doi.org/10.3390/pharmaceutics9040037] [PMID: 28934172]
[121]
Zhang Y, Cao Y, Meng X, Li C, Wang H, Zhang S. Enhancement of transdermal delivery of artemisinin using microemulsion vehicle based on ionic liquid and lidocaine ibuprofen. Colloids Surf B Biointerfaces 2020; 189: 110886.
[http://dx.doi.org/10.1016/j.colsurfb.2020.110886] [PMID: 32109824]
[122]
Callender SP, Mathews JA, Kobernyk K, Wettig SD. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery. Int J Pharm 2017; 526(1-2): 425-42.
[http://dx.doi.org/10.1016/j.ijpharm.2017.05.005] [PMID: 28495500]
[123]
Singh V, Bushettii SS, Appala Raju S, Ahmad R, Singh M, Bisht A. Microemulsions as promising delivery systems: a review. Indian J Pharm Educ Res 2011; 45(4): 392-401.
[124]
Espinoza LC, Vacacela M, Clares B, Garcia ML, Fabrega MJ, Calpena AC. Development of a nasal donepezil-loaded microemulsion for the treatment of Alzheimer’s disease: in vitro and ex vivo characterization. CNS Neurol Disord Drug Targets 2018; 17(1): 43-53.
[http://dx.doi.org/10.2174/1871527317666180104122347] [PMID: 29299992]
[125]
Shinde RL, Jindal AB, Devarajan PV. Microemulsions and nanoemulsions for targeted drug delivery to the brain. Curr Nanosci 2011; 7(1): 119-33.
[http://dx.doi.org/10.2174/157341311794480282]
[126]
Hellweg T, Gradzielski M, Farago B, Langevin D. Shape fluctuations of microemulsion droplets: a neutron spin-echo study. Colloids Surf A Physicochem Eng Asp 2001; 183-185: 159-69.
[http://dx.doi.org/10.1016/S0927-7757(01)00567-2]
[127]
Ghosh V, Mukherjee A, Chandrasekaran N. Mustard oil microemulsion formulation and evaluation of bactericidal activity. Int J Pharm Pharm Sci 2012; 4(4): 497-500.
[128]
Shingitha KP. Futuristic drug delivery system microemulsions: a review. PharmaTutor 2014; 2(3): 54-60.
[129]
Singh PK, Kashif Iqubal M, Shukla VK, Shuaib M. Microemulsions: current trends in novel drug delivery systems. J Pharm Chem Biol Sci 2014; 1(11): 39-5139.
[130]
Karande P, Mitragotri S. Enhancement of transdermal drug delivery via synergistic action of chemicals. Biochim Biophys Acta 2009; 1788(11): 2362-73.
[http://dx.doi.org/10.1016/j.bbamem.2009.08.015] [PMID: 19733150]
[131]
Shinde UA, Modani SH, Singh KH. Design and development of repaglinide microemulsion gel for transdermal delivery. AAPS PharmSciTech 2018; 19(1): 315-25.
[http://dx.doi.org/10.1208/s12249-017-0811-4] [PMID: 28717973]
[132]
Shukla T, Upmanyu N, Agrawal M, Saraf S, Saraf S, Alexander A. Biomedical applications of microemulsion through dermal and transdermal route. Biomed Pharmacother 2018; 108: 1477-94.
[http://dx.doi.org/10.1016/j.biopha.2018.10.021] [PMID: 30372850]
[133]
Chaiyana W, Rades T, Okonogi S. Characterization and in vitro permeation study of microemulsions and liquid crystalline systems containing the anticholinesterase alkaloidal extract from Tabernaemontana divaricata. Int J Pharm 2013; 452(1-2): 201-10.
[http://dx.doi.org/10.1016/j.ijpharm.2013.05.005] [PMID: 23680734]
[134]
Mendes IT, Ruela ALM, Carvalho FC, Freitas JTJ, Bonfilio R, Pereira GR. Development and characterization of nanostructured lipid carrier-based gels for the transdermal delivery of donepezil. Colloids Surf B Biointerfaces 2019; 177: 274-81.
[http://dx.doi.org/10.1016/j.colsurfb.2019.02.007] [PMID: 30763792]
[135]
Setya S, Madaan T, Razdan BK, Farswan M, Talegaonkar S. Design and development of novel transdermal nanoemulgel for Alzheimer’s disease: pharmacokinetic, pharmacodynamic and biochemical investigations. Curr Drug Deliv 2019; 16(10): 902-12.
[http://dx.doi.org/10.2174/1567201816666191022105036] [PMID: 31642410]
[136]
Moghaddam AA, Aqil M, Ahmad FJ, Ali MM, Sultana Y, Ali A. Nanoethosomes mediated transdermal delivery of vinpocetine for management of Alzheimer’s disease. Drug Deliv 2015; 22(8): 1018-26.
[http://dx.doi.org/10.3109/10717544.2013.846433] [PMID: 24717007]
[137]
Sabri AH, Kim Y, Marlow M, et al. Intradermal and transdermal drug delivery using microneedles - Fabrication, performance evaluation and application to lymphatic delivery. Adv Drug Deliv Rev 2020; 153: 195-215.
[http://dx.doi.org/10.1016/j.addr.2019.10.004] [PMID: 31634516]
[138]
Fonseca DFS, Vilela C, Silvestre AJD, Freire CSR. A compendium of current developments on polysaccharide and protein-based microneedles. Int J Biol Macromol 2019; 136: 704-28.
[http://dx.doi.org/10.1016/j.ijbiomac.2019.04.163] [PMID: 31028807]
[139]
Lee K, Goudie MJ, Tebon P, et al. Non-transdermal microneedles for advanced drug delivery. Adv Drug Deliv Rev 2019. Epub ahead of print
[http://dx.doi.org/10.1016/j.addr.2019.11.010]
[140]
Larrañeta E, Lutton REM, Woolfson AD, Donnelly RF. Microneedle arrays as transdermal and intradermal drug delivery systems: materials science, manufacture and commercial development mater. Sci Eng R Reports 2016; 104: 1-32.
[141]
Lee KJ, Jeong SS, Roh DH, Kim DY, Choi K, Lee EH. A practical guide to the development of microneedle systems. Int J Pharm 2019; 573: 118778.
[142]
Kim JY, Han MR, Kim YH, Shin SW, Nam SY, Park JH. Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer’s disease. Eur J Pharm Biopharm 2016; 105: 148-55.
[http://dx.doi.org/10.1016/j.ejpb.2016.06.006] [PMID: 27288938]
[143]
Matsuo K, Okamoto H, Kawai Y, et al. Vaccine efficacy of transcutaneous immunization with amyloid β using a dissolving microneedle array in a mouse model of Alzheimer’s disease. J Neuroimmunol 2014; 266(1-2): 1-11.
[http://dx.doi.org/10.1016/j.jneuroim.2013.11.002] [PMID: 24315156]
[144]
Won KN, Kyuri L, Sang LM, Hoon JJ. Efficient delivery DNA vaccine for Alzheimer’s disease by triggered release of polyplexes from microneedles. Mol Ther 2013; 21: S220.
[http://dx.doi.org/10.1016/S1525-0016(16)34908-5]
[145]
Takeuchi I, Takeshita T, Suzuki T, Makino K. Iontophoretic transdermal delivery using chitosan-coated PLGA nanoparticles for positively charged drugs. Colloids Surf B Biointerfaces 2017; 160: 520-6.
[http://dx.doi.org/10.1016/j.colsurfb.2017.10.011] [PMID: 29017147]
[146]
Choi J, Choi MK, Chong S, Chung SJ, Shim CK, Kim DD. Effect of fatty acids on the transdermal delivery of donepezil: in vitro and in vivo evaluation. Int J Pharm 2012; 422(1-2): 83-90.
[http://dx.doi.org/10.1016/j.ijpharm.2011.10.031] [PMID: 22037444]
[147]
Nan L, Liu C, Li Q, et al. Investigation of the enhancement effect of the natural transdermal permeation enhancers from Ledum palustre L. var. angustum N. Busch: mechanistic insight based on interaction among drug, enhancers and skin. Eur J Pharm Sci 2018; 124: 105-13.
[http://dx.doi.org/10.1016/j.ejps.2018.08.025] [PMID: 30153525]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 5
Year: 2020
Page: [360 - 373]
Pages: 14
DOI: 10.2174/1871527319666200618150046
Price: $65

Article Metrics

PDF: 85
HTML: 1