Generic placeholder image

Current Drug Delivery

Editor-in-Chief

ISSN (Print): 1567-2018
ISSN (Online): 1875-5704

Research Article

Engineering of Nanospheres Dispersed Microneedle System for Antihypertensive Action

Author(s): Mrunmayi Sardesai and Pravin Shende*

Volume 17 , Issue 9 , 2020

Page: [776 - 786] Pages: 11

DOI: 10.2174/1567201817666200804110003

Price: $65

Abstract

Background: A combinational therapy is mostly preferred in hypertension treatment because of low-dose and less side effects like pretibial edema, and gastrointestinal bleeding.

Objective: So the objective of the present work was to formulate an advanced drug delivery system in the form of bio-responsive microneedles by incorporating nifedipine, a cardiodepressant and diltiazem, a vasodilator for effective synergism in the treatment of hypertension.

Methods: The pH-responsive PLGA nanospheres of diltiazem were formulated using Water-in-Oil-in- Water (W/O/W) double emulsion and solvent-diffusion-evaporation technique. These nanospheres were added to nifedipine-PVP mixture and then incorporated into mold to develop microneedles.

Results: The microneedles showed the release of nifedipine almost 96.93± 2.31% for 24 h due to high PVP solubilization. The nanospheres of diltiazem on contact with acidic pH of skin managed to form of CO2 bubbles and increase the internal pressure to burst PLGA shell due to pore formation. The mean blood pressure observed for the normal group was 89.58 ± 3.603 mmHg, whereas the treatment with the new formulation significantly reduced the mean blood pressure up to 84.11 ± 2.98 mmHg in comparison to the disease control group (109.9 ± 1.825 mm Hg).

Conclusion: This system co-delivers the drugs nifedipine and diltiazem in hypertension and shows an advance alternative approach over conventional drug delivery system.

Keywords: Hypertension, nanospheres, microneedles, nifedipine, diltiazem, vasodilator.

Graphical Abstract
[1]
Neupane, R.; Boddu, S.H.S.; Renukuntla, J.; Babu, R.J.; Tiwari, A.K. Alternatives to biological skin in permeation studies: current trends and possibilities. Pharmaceutics, 2020, 12(2), 152.
[http://dx.doi.org/10.3390/pharmaceutics12020152 ] [PMID: 32070011]
[2]
Kolhar, P.; Doshi, N.; Mitragotri, S. Polymer nanoneedle-mediated intracellular drug delivery. Small, 2011, 7(14), 2094-2100.
[http://dx.doi.org/10.1002/smll.201100497 ] [PMID: 21695782]
[3]
Yang, J.; Liu, X.; Fu, Y.; Song, Y. Recent advances of microneedles for biomedical applications: drug delivery and beyond; Acta Pharma. Sin. B, 2019, pp. 4177-4183.
[4]
Kim, Y.C.; Park, J.H.; Prausnitz, M.R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev., 2012, 64(14), 1547-1568.
[http://dx.doi.org/10.1016/j.addr.2012.04.005 ] [PMID: 22575858]
[5]
Shende, P.; Sardesai, M.; Gaud, R.S. Micro to nanoneedles: a trend of modernized transepidermal drug delivery system. Artif. Cells Nanomed. Biotechnol., 2018, 46(1), 19-25.
[http://dx.doi.org/10.1080/21691401.2017.1304409 ] [PMID: 28355887]
[6]
Hong, X.; Wu, Z.C.; Lizhu, Z.; Wu, F.; Wei, L.; Yuan, W. Hydrogel Microneedle array for trandermal. Drug Delivery, Nano-Micr. Lett., 2014, 3, 191-199.
[7]
Pawar, S.; Shende, P. 22 factorial design-based biocompatible microneedle arrays containing artemether co-loaded with lumefantrine nanoparticles for transepidermal delivery. Biomed. Microdevices, 2020, 22(1), 19.
[http://dx.doi.org/10.1007/s10544-020-0476-8 ] [PMID: 32076890]
[8]
Zhang, Y.; Chai, D.; Gao, M.; Xu, B.; Jiang, G. Thermal ablation of separable microneedles for transdermal delivery of metformin on diabetic rats. Int. J. Polym. Mater. Pol., 2019, 68, 850-858.
[http://dx.doi.org/10.1080/00914037.2018.1517347]
[9]
Zhang, Y.; Jiang, G.; Hong, W.; Gao, M.; Xu, B.; Zhu, J.; Song, G.; Liu, T. Polymeric microneedles integrated with metformin-loaded and PDA/LA-coated hollow mesoporous SiO2 for NIR-triggered transdermal delivery on diabetic rats. ACS Appl. Bio. Mater., 2018, 6, 1906-1917.
[http://dx.doi.org/10.1021/acsabm.8b00470]
[10]
Zhang, Y.; Wang, D.; Gao, M.; Xu, B.; Zhu, J.; Yu, W.; Liu, D.; Jiang, G. Separable microneedles for near-infrared light-triggered transdermal delivery of metformin in diabetic rats. ACS Biomater. Sci. Eng., 2018, 8, 2879-2888.
[http://dx.doi.org/10.1021/acsbiomaterials.8b00642]
[11]
Roberts, M.E.; Epstein, B.J. Optimizing management of hypertension with combination therapy: considerations for the nurse practitioner. J. Cardiovasc. Nurs., 2009, 24(5), 380-389.
[http://dx.doi.org/10.1097/JCN.0b013e3181aed18e ] [PMID: 19707098]
[12]
Striessnig, J.; Ortner, N.J.; Pinggera, A. Pharmacology of L-type calcium channels: novel drugs for old targets? Curr. Mol. Pharmacol., 2015, 8(2), 110-122.
[http://dx.doi.org/10.2174/1874467208666150507105845 ] [PMID: 25966690]
[13]
McConville, A.; Hegarty, C.; Davis, J. Mini-review: assessing the potential impact of microneedle technologies on home healthcare applications. Medicines (Basel), 2018, 5(2), 1-15.
[http://dx.doi.org/10.3390/medicines5020050 ] [PMID: 29890643]
[14]
Busse, J.C.; de Velasco, R.E.; Pellegrini, E.L. Combined use of nifedipine and diltiazem for the treatment of severe hypertension. South. Med. J., 1991, 84(4), 502-504.
[http://dx.doi.org/10.1097/00007611-199104000-00025 ] [PMID: 2014439]
[15]
Temkin, L.P. High-dose monotherapy and combination therapy with calcium channel blockers for angina. A comprehensive review of the literature. Am. J. Med., 1989, 86(1A), 23-27.
[http://dx.doi.org/10.1016/0002-9343(89)90006-5 ] [PMID: 2563636]
[16]
Toyosaki, N.; Toyo-oka, T.; Natsume, T.; Katsuki, T.; Tateishi, T.; Yaginuma, T.; Hosoda, S. Combination therapy with diltiazem and nifedipine in patients with effort angina pectoris. Circulation, 1988, 77(6), 1370-1375.
[http://dx.doi.org/10.1161/01.CIR.77.6.1370 ] [PMID: 3286041]
[18]
Ke, C.J.; Lin, Y.J.; Hu, Y.C.; Chiang, W.L.; Chen, K.J.; Yang, W.C.; Liu, H.L.; Fu, C.C.; Sung, H.W. Multidrug release based on microneedle arrays filled with pH-responsive PLGA hollow microspheres. Biomaterials, 2012, 33(20), 5156-5165.
[http://dx.doi.org/10.1016/j.biomaterials.2012.03.056 ] [PMID: 22484044]
[19]
Gupta, J.; Mohan, G.; Prabakaran, L.; Gupta, R. Emulsion solvent diffusion evaporation technique: formulation design optimization and investigation of aceclofenac loaded ethyl cellulose microspheres. Int. J. Drug Dev. Res., 2013, 4, 336-349.
[20]
Denet, A.R.; Vanbever, R.; Préat, V. Skin electroporation for transdermal and topical delivery. Adv. Drug Deliv. Rev., 2004, 56(5), 659-674.
[http://dx.doi.org/10.1016/j.addr.2003.10.027 ] [PMID: 15019751]
[21]
Matsumoto, A.; Matsukawa, Y.; Horikiri, Y.; Suzuki, T. Rupture and drug release characteristics of multi-reservoir type microspheres with poly(dl-lactide-co-glycolide) and poly(dl-lactide). Int. J. Pharm., 2006, 327(1-2), 110-116.
[http://dx.doi.org/10.1016/j.ijpharm.2006.07.055 ] [PMID: 16971073]
[22]
Sánchez-López, E.; Egea, M.A.; Cano, A.; Espina, M.; Calpena, A.C.; Ettcheto, M.; Camins, A.; Souto, E.B.; Silva, A.M.; García, M.L. PEGylated PLGA nanospheres optimized by design of experiments for ocular administration of dexibuprofen-in vitro, ex vivo and in vivo characterization. Colloids Surf. B Biointerfaces, 2016, 145, 241-250.
[http://dx.doi.org/10.1016/j.colsurfb.2016.04.054 ] [PMID: 27187188]
[23]
Davis, S.P.; Landis, B.J.; Adams, Z.H.; Allen, M.G.; Prausnitz, M.R. Insertion of microneedles into skin: measurement and prediction of insertion force and needle fracture force. J. Biomech., 2004, 37(8), 1155-1163.
[PMID: 15212920]
[24]
Langer, R. Drug delivery and targeting. Nature, 1998, 392(6679), S5-S10.
[PMID: 9579855]
[25]
Lin, W.; Cormier, M.; Samiee, A.; Griffin, A.; Johnson, B.; Teng, C.L.; Hardee, G.E.; Daddona, P.E. Transdermal delivery of antisense oligonucleotides with microprojection patch (Macroflux) technology. Pharm. Res., 2001, 18(12), 1789-1793.
[http://dx.doi.org/10.1023/A:1013395102049 ] [PMID: 11785702]
[26]
Limpongsa, E.; Umprayn, K. Preparation and evaluation of diltiazem hydrochloride diffusion-controlled transdermal delivery system. AAPS PharmSciTech, 2008, 9(2), 464-470.
[http://dx.doi.org/10.1208/s12249-008-9062-8 ] [PMID: 18431661]
[27]
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]
[28]
Shende, P.; Salunke, M. Transepidermal microneedles for co-administration of folic acid with methotrexate in the treatment of rheumatoid arthritis. Biomed. Phys. Eng. Express, 2019, 5, e025023.
[http://dx.doi.org/10.1088/2057-1976/aafbbb]
[29]
Prida, X.E.; Gelman, J.S.; Feldman, R.L.; Hill, J.A.; Pepine, C.J.; Scott, E. Comparison of diltiazem and nifedipine alone and in combination in patients with coronary artery spasm. J. Am. Coll. Cardiol., 1987, 9(2), 412-419.
[http://dx.doi.org/10.1016/S0735-1097(87)80397-2 ] [PMID: 3543092]

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy