Abstract
A soft transdermal drug-delivery (TDD) patch composed of deproteinized natural rubber (DPNR) was fabricated in this work. Sulindac (Sul), an anionic drug, was loaded on the DPNR patch using silicone oil as a plasticizer. The in vitro release-permeation behavior of Sul from the Sul-loaded DPNR patch was studied by using a modified Franz diffusion cell at a pH of 7.4 and temperature of 37 °C. A cytotoxicity test of the DPNR with silicone oil (DPNR-Si) patch was performed, and the viability percentage was 90%. When external electrical potentials of 0–9 V were applied, the maximum amounts of Sul released and permeated from the Sul-loaded DPNR patch were 8.34, 10.16, 11.86, 19.84, 54.73, 70.89, 82.25, and 83.02% for electrical potentials of 0, 0.1, 0.3, 1, 3, 5, 7, and 9 V, respectively. The release and permeation amount of Sul increased with the increasing electrical potential because of the electrorepulsive force, expanded pathway in pigskin, and pore formation in DPNR. Pore formation occurred under an applied electric field, as confirmed by optical micrographs. The porosity percentage increased with the increasing time and electrical potential due to the drug release and permeation and lack of plasticizer. The effect of storage time on the permeation characteristics was studied for 3 months. The release and permeation amount of Sul was 8.61 and 6.80 wt% for storage times of 1 and 3 months, respectively. Thus, the fabricated Sul-loaded DPNR patch is an electrically controllable TDD patch.
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Bhowmik D, Bhattacharjee C, Chandira M, Jayakar B, Sampath KP (2010) Recent advances in transdermal drug delivery system. Int J PharmTech Res 2(1):68–77
Xie Y, Xu BH, Gao Y (2005) Controlled transdermal delivery of model drug cpmpound by MEMS microneedle array. Nanomed J 1:184–190
Prausnitz MR, Langer R (2008) Transdermal drug delivery. Nat Biotechnol 26(11):1261–1268
Bose S, Ravis WR, Lin YJ, Zhang L, Hofmann GA, Banga AK (2001) Electrically-assisted transdermal delivery of buprenorphine. J Control Release 73:197–203
Pikal MJ (2001) The role of electroosmotic flow in transdermal iontophoresis. Adv Drug Deliv Rev 46:281–305
Gupta P, Vermani K, Garg S (2002) Hydrogel: from controlled release to pH-responsive drug delivery. Drug Discov Today 7(10):569–579
Thorngkham P, Paradee N, Niamlang S, Sirivat A (2015) Permeation study of indomethacin from polycarbazole/natural rubber blend film for electric field controlled transdermal delivery. J Pharm Sci 104:1795–1803
Snorradottir BS, Gudnason PI, Thorsteinsson F, Masson M (2011) Experimental design for optimizing drug release from silicone elastomer matrix and investigation of transdermal drug delivery. Eur J Pharm Sci 42:559–567
Rippel MM, Leite CAP, Lee LT, Galembeck F (2005) Formation of calcium crystallites in dry natural rubber particles. J Colloid Interface Sci 288:449–456
Suksaeree J, Boonme P, Taweepreda W, Ritthidej GC, Pichayakorn W (2012) Characterization in vitro release and permeation studies of nicotine transdermal patches prepared from deproteinized natural rubber latex blends. Chem Eng Res Des 90:906–914
Floriano JF, Barros NR, Cinman JLF, Silva RG, Loffredo AV, Borges FA, Norberto AMQ, Chagas ALD, Garms BC, Graeff CFO, Herculano RD (2017) Ketoprofen loaded in natural rubber latex transdermal patch for tendinitis treatment. J Polym Environ. https://doi.org/10.1007/s10924-017-1127-x
Afreen S, Haque KR, Huda MK (2013) Troubleshooting for the observed problems in processing latex concentrate from natural resource. IOP Conf Ser Earth Environ Sci 16:012007
Perrella FW, Gaspari AA (2002) Natural rubber latex protein reduction with an emphasis on enzyme treatment. Methods 27:77–86
Paradee N, Sirivat A (2014) Electrically controlled release of benzoic acid from poly(3,4-ethylenedioxythiophene)/alginate matrix: effect of conductive poly(3,4-ethylenedioxythiophene. Morphol J Phys Chem 118:9263 – 9271
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA (1983) Mechanisms of solute release from porous hydrophilic polymers. Int J Pharm 15(1):25–35
Higuchi T (1963) Mechanism of sustained-action medication: theoretical analysis of rate of release of solid drug dispersed in solid matrices. J Pharm Sci 2:1145–1149
Ozdemir KG, Yilmaz H, Yilmaz S (2009) In vitro evaluation of cytotoxicity of soft liming materials on L929 Cells by MTT assay. J Biomed Mater Res B 90:82–86. https://doi.org/10.1002/jbm.b.31256
Bouillaguet S, Shaw L, Gonzalez L, Wataha JC, Krejci I (2002) Long-term cytotoxicity of resin-based dental restorative materials. J Oral Rehabil 29:7–13
Sussman GL, Beezhold DH, Kurup VP (2002) Allergens and natural rubber proteins. J Allergy Clin Immunol 110:33–39
Nawamawat K, Sakdapipanich JT, Ho CC (2010) Effect of deproteinized methods on the proteins and properties of natural rubber latex during storage. Macromol Symp 288:95–103
Aprem AS, Pal SN (2002) Latex allergy and recent development in deproteinsation of natural rubber latex. J Rubber Res 5(2):94–134
Lee JH, Lee EJ, Kwon JS, Hwang CJ, Kim KN (2014) Cytotoxicity comparison of the nanoparticles deposited on latex rubber between the original and stertched state. J Nanomater. https://doi.org/10.1155/2014/567827
Herculano RD, Guimaraes SAC, Belmonte GC, Duarte MAH, Junior ONO, Kinoshita A, Graeff CFO (2010) Metronidazole release using natural rubber latex as matrix. Mater Res 13:57–61
Shazly GA (2016) Effect of sulindac binary system on in vitro and vivo release profiles: an assessment of polymer type and its ratio. BioMed Res Int. https://doi.org/10.1155/2016/3182358
Cavallari C, Tarterini F, Fini A (2016) Thermal characterization of some polymer solvates of the anti-inflammatory/anti-cancer sulindac. Thermochim Acta 633:129–139
Paradee N, Sirivat A, Niamlang S, Prissanaroom-Ouajai W (2012) Effect of crosslinking ratio model drug, and electric field strength on electrically controlled release for alginate-based hydrogel. Mater J Sci 23:999–1010
Sittiwong J, Niamlang S, Paradee N, Sirivat A (2012) Electric field-controlled benzoic acid and sulphanilamide delivery from poly(vinyl alcohol) hydrogel. J AAPS PharmSciTech 13:1407–1415
Juntanon K, Niamlang S, Rujiravanit R, Sirivat A (2008) Electrically controlled release of sulfosalicylic acid from crosslinked poly(vinyl alcohol) hydrogel. Int J Pharm 356:1–11
Weaver JC, Vaughan TE, Chizmadzhev Y (1999) Theory of electrical creation of aqueous pathways across skin transport barriers. Adv Drug Deliv Rev 35:21–39
Barros NR, Miranda MCR, Borges FA, Gemeinder JLP, Mendonça RJ, Cilli EM, Herculano RD (2017) Natural rubber latex: development and in vitro characterization of a future transdermal patch for enuresis treatment. Int J Polym Mater. https://doi.org/10.1080/00914037.2017.1280795
Acknowledgements
This work was financially supported by the Conductive and Electroactive Polymer Research Unit of Chulalongkorn University, the Advance Materials Research Group, RMUTT, the Thailand Research Fund (TRF) and the Royal Thai Government.
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Banpean, A., Paradee, N., Sirivat, A. et al. Deproteinized Natural Rubber as an Electrically Controllable, Transdermal Drug-Delivery Patch. J Polym Environ 26, 3745–3753 (2018). https://doi.org/10.1007/s10924-018-1252-1
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DOI: https://doi.org/10.1007/s10924-018-1252-1