Abstract
Background: As episodes of acute migraine for migraineurs, a self-treatment that promptly relieves headaches and eliminates the associated symptoms would be optimal. Based on the consideration, a rapidly dissolving double-layer microneedles derived from natural acacia was developed.
Methods: Under the optimized reaction conditions that was screened out through orthogonal designing test, acacia (GA) was conducted on the ionic crosslinking, a prescribed amount of cross-linking composites was applied to fabricate the double-layer microneedles loaded with sumatriptan at the tip. The mechanical strength and dissolving capability of penetrating pigskin along with in vitro release were measured. The component and content of the resulting compound were determined with FT-IR and thermal analysis, and the bonding state of cross-linker was characterized using X-ray photoelectron spectroscopy.
Results: Each needle from the constructed microneedles with the maximal drug loading consisted of the crosslinking acacia of around 10.89 μg and the encapsulated sumatriptan of around 1.821 μg. Apart from the excellent solubility, the formed microneedles possessed enough mechanical stiffness to penetrate the multilayer parafilm. The histological section of the pigskin confirmed the insertion depth of the microneedles could reach 300 ± 28 μm, and the needle bulk in the isolated pigskin could be totally dissolved within 240 s. Franz diffusion study displayed that an almost entire release of the encapsulated drug might be realized within 40 min. The coagulum created from crosslinking was composed of -COOof glucuronic acid in the component of acacia and the added crosslinker to form a double coordination bond, and the crosslinking percentage reached about 13%.
Conclusion: The release amount of drug from 12 patches made of the prepared microneedles was comparable to that of subcutaneous injection, providing a new possibility for migraine treatment.
Graphical Abstract
[1]
Landy, S.; Munjal, S.; Brand-Schieber, E.; Rapoport, A.M. Efficacy and safety of DFN-11 (sumatriptan injection, 3mg) in adults with episodic migraine: A multicenter, randomized, double-blind, placebo-controlled study. J. Headache Pain, 2018, 19, 1-9.
[2]
Woldeamanuel, Y.W.; Cowan, R.P. Migraine affects 1 in 10 people worldwide featuring recent rise: A systematic review and meta-analysis of community-based studies involving 6 million participants. J. Neurol. Sci., 2017, 372, 307-315.
[http://dx.doi.org/10.1016/j.jns.2016.11.071] [PMID: 28017235]
[http://dx.doi.org/10.1016/j.jns.2016.11.071] [PMID: 28017235]
[4]
Lipton, R.B.; Stewart, W.F.; Scher, A.I. Epidemiology and economic impact of migraine. Curr. Med. Res. Opin., 2001, 17((sup1)), s4-s12.
[http://dx.doi.org/10.1185/0300799039117005]
[http://dx.doi.org/10.1185/0300799039117005]
[5]
Woldeamanuel, Y.W.; Andreou, A.P.; Cowan, R.P. Prevalence of migraine headache and its weight on neurological burden in Africa: A 43-year systematic review and meta-analysis of community-based studies. J. Neurol. Sci., 2014, 342(1-2), 1-15.
[http://dx.doi.org/10.1016/j.jns.2014.04.019] [PMID: 24814950]
[http://dx.doi.org/10.1016/j.jns.2014.04.019] [PMID: 24814950]
[6]
Ahmed Kassem, A. Formulation approaches of triptans for management of migraine. Curr. Drug Deliv., 2016, 13(6), 882-898.
[http://dx.doi.org/10.2174/1567201813666160425112600] [PMID: 27109335]
[http://dx.doi.org/10.2174/1567201813666160425112600] [PMID: 27109335]
[7]
Joe, N.; Hayley, L.; Ashley, Q.; Ngoc, D.A.; Guillaume, H.; Mahmoud, A. Pharmacokinetics and skin tolerability of intracutaneous zolmitriptan delivery in swine using Adhesive Dermally-Applied Microarray (ADAM). J. Pharm., 2018, 107, 2192-2219.
[8]
Jhee, S.S.; Shiovitz, T.; Crawford, A.W.; Cutler, N.R. Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents. Clin. Pharmacokinet., 2001, 40(3), 189-205.
[http://dx.doi.org/10.2165/00003088-200140030-00004]
[http://dx.doi.org/10.2165/00003088-200140030-00004]
[9]
Rothrock, J.F. Injectable sumatriptan: Now needle-based or needle-free. Headache, 2010, 50(2), 343-344.
[http://dx.doi.org/10.1111/j.1526-4610.2009.01602.x] [PMID: 20456140]
[http://dx.doi.org/10.1111/j.1526-4610.2009.01602.x] [PMID: 20456140]
[10]
Nalluri, B.N.; Anusha, S.S.V.; Bramhini, S.R.; Amulya, J.; Sultana, A.S.K.; Teja, C.U.; Das, D.S. In vitro skin permeation enhancement of sumatriptan by microneedle application. Curr. Drug Deliv., 2015, 12, 761-769.
[http://dx.doi.org/10.2174/1567201812666150304123150]
[http://dx.doi.org/10.2174/1567201812666150304123150]
[11]
Ronnander, P.; Simon, L.; Spilgies, H.; Koch, A.; Scherr, S. Dissolving polyvinylpyrrolidone-based microneedle systems for in vitro delivery of sumatriptan succinate. Eur. J. Pharm. Sci., 2018, 114, 84-92.
[http://dx.doi.org/10.1016/j.ejps.2017.11.031] [PMID: 29203152]
[http://dx.doi.org/10.1016/j.ejps.2017.11.031] [PMID: 29203152]
[12]
Ronnander, J.P.; Simon, L.; Koch, A. Transdermal delivery of sumatriptan succinate using iontophoresis and dissolving microneedles. J. Pharm. Sci., 2019, 108(11), 3649-3656.
[http://dx.doi.org/10.1016/j.xphs.2019.07.020]
[http://dx.doi.org/10.1016/j.xphs.2019.07.020]
[13]
Ito, Y.; Kashiwara, S.; Fukushima, K.; Takada, K. Two-layered dissolving microneedles for percutaneous delivery of sumatriptan in rats. Drug Dev. Ind. Pharm., 2011, 37(12), 1387-1393.
[http://dx.doi.org/10.3109/03639045.2011.576426] [PMID: 21545233]
[http://dx.doi.org/10.3109/03639045.2011.576426] [PMID: 21545233]
[14]
Wu, D.; Quan, Y.; Kamiyama, F.; Kusamori, K.; Katsumi, H.; Sakane, T.; Yamamoto, A. Improvement of transdermal delivery of sumatriptan succinate using a novel self-dissolving microneedle array fabricated from sodium hyaluronate in rats. Biol. Pharm. Bull., 2015, 38(3), 365-373.
[http://dx.doi.org/10.1248/bpb.b14-00502] [PMID: 25757917]
[http://dx.doi.org/10.1248/bpb.b14-00502] [PMID: 25757917]
[15]
Wu, D.; Katsumi, H.; Quan, Y.; Kamiyama, F.; Kusamori, K.; Sakane, T.; Yamamoto, A. Permeation of sumatriptan succinate across human skin using multiple types of self-dissolving microneedle arrays fabricated from sodium hyaluronate. J. Drug Target., 2016, 24(8), 752-758.
[http://dx.doi.org/10.3109/1061186X.2016.1154565] [PMID: 26878569]
[http://dx.doi.org/10.3109/1061186X.2016.1154565] [PMID: 26878569]
[16]
Lee, J.; Park, S.H.; Seo, I.H.; Lee, K.J.; Ryu, W. Rapid and repeatable fabrication of high A/R silk fibroin microneedles using thermally-drawn micromolds. Eur. J. Pharm. Biopharm., 2015, 94, 11-19.
[http://dx.doi.org/10.1016/j.ejpb.2015.04.024] [PMID: 25936857]
[http://dx.doi.org/10.1016/j.ejpb.2015.04.024] [PMID: 25936857]
[17]
Chen, M.C.; Ling, M.H.; Kusuma, S.J. Poly-γ-glutamic acid microneedles with a supporting structure design as a potential tool for transdermal delivery of insulin. Acta Biomater., 2015, 24, 106-116.
[http://dx.doi.org/10.1016/j.actbio.2015.06.021] [PMID: 26102333]
[http://dx.doi.org/10.1016/j.actbio.2015.06.021] [PMID: 26102333]
[18]
Li, G.; Badkar, A.; Nema, S.; Kolli, C.S.; Banga, A.K. In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int. J. Pharm., 2009, 368(1-2), 109-115.
[http://dx.doi.org/10.1016/j.ijpharm.2008.10.008] [PMID: 18996461]
[http://dx.doi.org/10.1016/j.ijpharm.2008.10.008] [PMID: 18996461]
[19]
Lee, J.W.; Park, J.H.; Prausnitz, M.R. Dissolving microneedles for transdermal drug delivery. Biomaterials, 2008, 29(13), 2113-2124.
[http://dx.doi.org/10.1016/j.biomaterials.2007.12.048] [PMID: 18261792]
[http://dx.doi.org/10.1016/j.biomaterials.2007.12.048] [PMID: 18261792]
[20]
Hirobe, S.; Azukizawa, H.; Hanafusa, T.; Matsuo, K.; Quan, Y-S.; Kamiyama, F.; Katayama, I.; Okada, N.; Nakagawa, S. Clinical study and stability assessment of a novel transcutaneous influenza vaccination using a dissolving microneedle patch. Biomaterials, 2015, 57, 50-58.
[http://dx.doi.org/10.1016/j.biomaterials.2015.04.007]
[http://dx.doi.org/10.1016/j.biomaterials.2015.04.007]
[21]
Park, Y.; Kim, K.S.; Chung, M.; Sung, J.H.; Kim, B. Fabrication and characterization of dissolving microneedle arrays for improving skin permeability of cosmetic ingredients. J. Ind. Eng. Chem., 2016, 39, 121-126.
[http://dx.doi.org/10.1016/j.jiec.2016.05.022]
[http://dx.doi.org/10.1016/j.jiec.2016.05.022]
[22]
Larrañeta, E.; Lutton, R.E.M.; Woolfson, A.D.; Donnelly, R.F. Microneedle arrays as transdermal and intradermal drug delivery systems: Materials science, manufacture and commercial development. Mater. Sci. Eng. Rep., 2016, 104, 1-32.
[http://dx.doi.org/10.1016/j.mser.2016.03.001]
[http://dx.doi.org/10.1016/j.mser.2016.03.001]
[23]
Renard, D.; Garnier, C.; Lapp, A.; Schmitt, C.; Sanchez, C. Structure of arabinogalactan-protein from Acacia gum: From porous ellipsoids to supramolecular architectures. Carbohydr. Polym., 2012, 90(1), 322-332.
[http://dx.doi.org/10.1016/j.carbpol.2012.05.046] [PMID: 24751048]
[http://dx.doi.org/10.1016/j.carbpol.2012.05.046] [PMID: 24751048]
[24]
Toti, U.S.; Soppimath, K.S.; Mallikarjuna, N.N.; Aminabhavi, T.M. Acrylamide-grafted-acacia gum polymer matrix tablets as erosion-controlled drug delivery systems. J. Appl. Polym. Sci., 2004, 93(5), 2245-2253.
[http://dx.doi.org/10.1002/app.20768]
[http://dx.doi.org/10.1002/app.20768]
[25]
Sanchez, C.; Nigen, M.; Tamayo, V.M.; Doco, T.; Williams, P.; Amine, C.; Renard, D. Acacia gum: History of the future. Food Hydrocoll., 2018, 78, 140-160.
[26]
de Oliveira, J.L.; Campos, E.V.R.; Pereira, A.E.S.; Nunes, L.E.S.; da Silva, C.C.L.; Pasquoto, T.; Lima, R.; Smaniotto, G.; Polanczyk, R.A.; Fraceto, L.F. Geraniol encapsulated in chitosan/gum arabic nanoparticles: A promising system for pest management in sustainable agriculture. J. Agric. Food Chem., 2018, 66(21), 5325-5334.
[http://dx.doi.org/10.1021/acs.jafc.8b00331]
[http://dx.doi.org/10.1021/acs.jafc.8b00331]
[27]
Li, M.; Li, H.; Li, X.; Zhu, H.; Xu, Z.; Liu, L.; Ma, J.; Zhang, M. A bioinspired alginate-gum arabic hydrogel with micro-/nanoscale structures for controlled drug release in chronic wound healing. ACS Appl. Mater. Interfaces, 2017, 9(27), 22160-22175.
[http://dx.doi.org/10.1021/acsami.7b04428] [PMID: 28640580]
[http://dx.doi.org/10.1021/acsami.7b04428] [PMID: 28640580]
[28]
Chu, L.Y.; Choi, S.O.; Prausnitz, M.R. Fabrication of dissolving polymer microneedles for controlled drug encapsulation and delivery: Bubble and pedestal microneedle designs. J. Pharm. Sci., 2010, 99(10), 4228-4238.
[http://dx.doi.org/10.1002/jps.22140] [PMID: 20737630]
[http://dx.doi.org/10.1002/jps.22140] [PMID: 20737630]
[29]
Coyne, J.; Davis, B.; Kauffman, D.; Zhao, N.; Wang, Y. Polymer microneedle mediated local aptamer delivery for blocking the function of vascular endothelial growth factor. ACS Biomater. Sci. Eng., 2017, 3(12), 3395-3403.
[http://dx.doi.org/10.1021/acsbiomaterials.7b00718] [PMID: 29707631]
[http://dx.doi.org/10.1021/acsbiomaterials.7b00718] [PMID: 29707631]
[30]
Yu, W.; Jiang, G.; Zhang, Y.; Liu, D.; Xu, B.; Zhou, J. Polymer microneedles fabricated from alginate and hyaluronate for transdermal delivery of insulin. Mater. Sci. Eng. C, 2017, 80, 187-196.
[http://dx.doi.org/10.1016/j.msec.2017.05.143]
[http://dx.doi.org/10.1016/j.msec.2017.05.143]
[31]
Chinese Pharmacopoeia Committee. Vol. 1. Chinese Medicine Science and Technology Press. Beijing, China. Pharmacopoeia of the People's Republic of China , 2015; pp. 1249-1250.
[32]
Chiu, Y.H.; Chen, M.C.; Wan, S.W. Sodium hyaluronate/chitosan composite microneedles as a single-dose intradermal immunization system. Biomacromolecules, 2018, 19(6), 2278-2285.
[http://dx.doi.org/10.1021/acs.biomac.8b00441] [PMID: 29722966]
[http://dx.doi.org/10.1021/acs.biomac.8b00441] [PMID: 29722966]
[33]
Machekposhti, S.A.; Soltani, M.; Najafizadeh, P.; Ebrahimi, S.A.; Chen, P. Biocompatible polymer microneedle for transdermal delivery of tranexamic acid biocompatible polymer microneedle for transdermal delivery of tranexamic acid. J. Control. Release, 2017, 261, 87-92.
[34]
Plosker, G.L.; Mctavish, D. A reappraisal of its pharmacology and therapeutic efficacy in the acute treatment of migraine and cluster headache. Drugs, 1994, 47, 622-651.
[PMID: 7516861]
[PMID: 7516861]
[35]
Paredes, A.J.; Volpe-Zanutto, F.; Permana, A.D.; Murphy, A.J.; Picco, C.J.; Vora, L.K.; Coulter, J.A.; Donnelly, R.F. Novel tip-loaded dissolving and implantable microneedle array patches for sustained release of finasteride. Int. J. Pharm., 2021, 606.
[36]
Larra˜neta, E.; Moore, J.; Vicente-P’erez, E.M.; Gonz’alez-V’azquez, P.; Lutton, R.; Woolfson, A.D.; Donnelly, R.F. A proposed model membrane and test method for microneedle insertion studies. Int. J. Pharm., 2014, 472, 65-73.
[37]
Liu, W.; Guo, W.; Yang, M.; Zhang, X.; Wu, F. Grafted poly (vinyl alcohol) functionalized by folic acid and its transdermal microneedles. Polym. Bull., 2021, 5, 1-16.
[38]
Goodman and Gilman’s The Pharmacological Basis of Therapeutics; Brunton, L.L.; Chabner, B.A.; Knollmann, B.C.; Sanders-Bush, E.; Hazelwood, L., Eds.; McGraw-Hill: New York, 2011, pp. 381-417.
[39]
Renard, D.; Lickliter, J.; Mardell, J.; von Stein, T. Pharmacokinetics and tolerability of a new Intracutaneous microneedle system of Zolmitriptan (ZP-Zolmitriptan). Headache, 2016, 56, 5774-07030.
[40]
Renard, D.; Lavenant-Gourgeon, L.; Ralet, M.C.; Sanchez, C. Acacia senegal gum: continuum of molecular species differing by their protein to sugar ratio, molecular weight, and charges. Biomacromolecules, 2006, 7(9), 2637-2649.
[http://dx.doi.org/10.1021/bm060145j] [PMID: 16961328]
[http://dx.doi.org/10.1021/bm060145j] [PMID: 16961328]
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