Research Article

Fabrication, characterization and application of sugar microneedles for transdermal drug delivery

Hiep X Nguyen

Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA

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Ajay K Banga

*Author for correspondence:

E-mail Address: Banga_ak@mercer.edu

Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, Atlanta, GA 30341, USA

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Published Online:31 Mar 2017https://doi.org/10.4155/tde-2016-0096

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Abstract

Aim: This study aimed to fabricate, characterize and use maltose microneedles for transdermal delivery of doxorubicin. Materials & methods: Microneedles were fabricated by micromolding technique and evaluated for dimensions, mechanical properties and in situ dissolution. Microporation of human cadaver skin was confirmed by dye binding, histology, pore uniformity, confocal laser microscopy and skin integrity measurement. In vitro permeation studies were performed on vertical Franz diffusion cells. Results: Maltose microneedles were sharp, mechanically uniform and rapidly dissolvable. Microneedle insertion resulted in a marked decrease in lag time and a significant increase in the permeation across and into human skin (p < 0.05). The skin delivery profile was used to predict the steady-state plasma concentration. Conclusion: Maltose microneedles are a promising physical technique to increase skin delivery.

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Papers of special note have been highlighted as: • of interest; •• of considerable interest

References

1 Banga AK. Transdermal and Intradermal Delivery of Therapeutic Agents: Application of Physical Technologies. CRC Press, Boca Raton, FL, USA (2011).Crossref, Google Scholar
2 Kalluri H, Banga AK. Formation and closure of microchannels in skin following microporation. Pharm. Res. 28(1), 82–94 (2011).Crossref, Medline, CAS, Google Scholar
3 Banga AK. New technologies to allow transdermal delivery of therapeutic proteins and small water-soluble drugs. Am. J. Drug Deliv. 4(4), 221–230 (2006).Crossref, CAS, Google Scholar
4 Li G, Badkar A, Kalluri H, Banga AK. Microchannels created by sugar and metal microneedles: characterization by microscopy, macromolecular flux and other techniques. J. Pharm. Sci. 99(4), 1931–1941 (2010).Crossref, Medline, CAS, Google Scholar
5 Kolli CS, Banga AK. Characterization of solid maltose microneedles and their use for transdermal delivery. Pharm. Res. 25(1), 104–113 (2008). • Presents the methods to characterize microneedles and microchannels.Crossref, Medline, CAS, Google Scholar
6 Banga AK. Microporation applications for enhancing drug delivery. Expert Opin. Drug Deliv. 6(4), 343–354 (2009). •• Summarizes the mechanism and application of microporation to mediate transdermal drug delivery.Crossref, Medline, CAS, Google Scholar
7 Sachdeva V, Banga AK. Microneedles and their applications. Recent Pat. Drug Deliv. Formul. 5(2), 95–132 (2011).Crossref, Medline, CAS, Google Scholar
8 Li G, Badkar A, Nema S, Kolli CS, Banga AK. In vitro transdermal delivery of therapeutic antibodies using maltose microneedles. Int. J. Pharm. 368(1), 109–115 (2009). • Characterized maltose microneedles and used them to create microchannels to significantly enhance transdermal delivery of human IgG through full thickness hairless rat skin in vitro.Crossref, Medline, CAS, Google Scholar
9 Sullivan SP, Koutsonanos DG, Del Pilar Martin M et al. Dissolving polymer microneedle patches for influenza vaccination. Nat. Med. 16(8), 915–920 (2010).Crossref, Medline, CAS, Google Scholar
10 Singh ND, Banga AK. Controlled delivery of ropinirole hydrochloride through skin using modulated iontophoresis and microneedles. J. Drug Target. 21(4), 354–366 (2013).Crossref, Medline, CAS, Google Scholar
11 Katikaneni S, Badkar A, Nema S, Banga AK. Molecular charge mediated transport of a 13kD protein across microporated skin. Int. J. Pharm. 378(1), 93–100 (2009).Crossref, Medline, CAS, Google Scholar
12 Scott JA, Banga AK. Cosmetic devices based on active transdermal technologies. Ther. Deliv. 6(9), 1089–1099 (2015).Link, CAS, Google Scholar
13 Donnelly RF, Singh TRR, Tunney MM et al. Microneedle arrays allow lower microbial penetration than hypodermic needles in vitro. Pharm. Res. 26(11), 2513–2522 (2009).Crossref, Medline, CAS, Google Scholar
14 Prausnitz MR. Microneedles for transdermal drug delivery. Adv. Drug Deliv. Rev. 56(5), 581–587 (2004).Crossref, Medline, CAS, Google Scholar
15 Miyano T, Tobinaga Y, Kanno T et al. Sugar microneedles as transdermic drug delivery system. Biomed. Microdevices. 7(3), 185–188 (2005). •• Reports the process of fabricating maltose microneedles using melting technique.Crossref, Medline, CAS, Google Scholar
16 Park J-H, Allen MG, Prausnitz MR. Biodegradable polymer microneedles: fabrication, mechanics and transdermal drug delivery. J. Controlled Release. 104(1), 51–66 (2005).Crossref, Medline, CAS, Google Scholar
17 Martin CJ, Allender CJ, Brain KR, Morrissey A, Birchall JC. Low temperature fabrication of biodegradable sugar glass microneedles for transdermal drug delivery applications. J. Controlled Release 158(1), 93–101 (2012).Crossref, Medline, CAS, Google Scholar
18 Lee K, Lee CY, Jung H. Dissolving microneedles for transdermal drug administration prepared by stepwise controlled drawing of maltose. Biomaterials 32(11), 3134–3140 (2011).Crossref, Medline, CAS, Google Scholar
19 Nguyen HX, Banga AK. Enhanced skin delivery of vismodegib by microneedle treatment. Drug Deliv. Transl. Res. 5(4), 407–423 (2015). •• Investigated the effect of needle length, equilibration time and treatment duration on transdermal delivery of vismodegib in vitro.Crossref, Medline, CAS, Google Scholar
20 Vemulapalli V, Yang Y, Friden PM, Banga AK. Synergistic effect of iontophoresis and soluble microneedles for transdermal delivery of methotrexate. J. Pharm. Pharmacol. 60(1), 27–33 (2008).Crossref, Medline, CAS, Google Scholar
21 Gujjar M, Banga AK. Iontophoretic and microneedle mediated transdermal delivery of glycopyrrolate. Pharmaceutics 6(4), 663–671 (2014).Crossref, Medline, CAS, Google Scholar
22 Sachdeva V, Zhou Y, Banga AK. In vivo transdermal delivery of leuprolide using microneedles and iontophoresis. Curr. Pharm. Biotechnol. 14(2), 180–193 (2013).Medline, CAS, Google Scholar
23 Yang Y, Kalluri H, Banga AK. Effects of chemical and physical enhancement techniques on transdermal delivery of cyanocobalamin (vitamin B12) in vitro. Pharmaceutics 3(3), 474–484 (2011).Crossref, Medline, CAS, Google Scholar
24 Puri A, Nguyen HX, Banga AK. Microneedle-mediated intradermal delivery of epigallocatechin-3-gallate. Int. J. Cosmet. Sci. 38(5), 512–523 (2016).Crossref, Medline, CAS, Google Scholar
25 Wu J, Xu S, Jiang W, Shen Y, Pu M. Facile preparation of a pH-sensitive nano-magnetic targeted system to deliver doxorubicin to tumor tissues. Biotechnol. Lett. 37(3), 585–591 (2015).Crossref, Medline, CAS, Google Scholar
26 Taveira SF, Nomizo A, Lopez RF. Effect of the iontophoresis of a chitosan gel on doxorubicin skin penetration and cytotoxicity. J. Control. Rel. 134(1), 35–40 (2009).Crossref, Medline, CAS, Google Scholar
27 Kim JO, Kabanov AV, Bronich TK. Polymer micelles with cross-linked polyanion core for delivery of a cationic drug doxorubicin. J. Control. Rel. 138(3), 197–204 (2009).Crossref, Medline, CAS, Google Scholar
28 Herai H, Gratieri T, Thomazine JA, Bentley MVLB, Lopez RFV. Doxorubicin skin penetration from monoolein-containing propylene glycol formulations. Int. J. Pharm. 329(1), 88–93 (2007).Crossref, Medline, CAS, Google Scholar
29 Huber LA, Pereira TA, Ramos DN et al. Topical skin cancer therapy using doxorubicin-loaded cationic lipid nanoparticles and iontophoresis. J. Biomed. Nanotechnol. 11(11), 1975–1988 (2015).Crossref, Medline, CAS, Google Scholar
30 Taveira SF, De Santana DCAS, Araújo LMPC, Marquele-Oliveira F, Nomizo A, Lopez RFV. Effect of iontophoresis on topical delivery of doxorubicin-loaded solid lipid nanoparticles. J. Biomed. Nanotechnol. 10(7), 1382–1390 (2014).Crossref, Medline, CAS, Google Scholar
31 Chen M-C, Wang K-W, Chen D-H, Ling M-H, Liu C-Y. Remotely triggered release of small molecules from LaB6@SiO2-loaded polycaprolactone microneedles. Acta Biomater. 13, 344–353 (2015).Crossref, Medline, CAS, Google Scholar
32 Ma Y, Boese SE, Luo Z, Nitin N, Gill HS. Drug coated microneedles for minimally-invasive treatment of oral carcinomas: development and in vitro evaluation. Biomed. Microdevices. 17(2), 44 (2015).Crossref, Medline, Google Scholar
33 Mansoor I, Lai J, Ranamukhaarachchi S et al. A microneedle-based method for the characterization of diffusion in skin tissue using doxorubicin as a model drug. Biomed. Microdevices. 17(3), 9967 (2015).Crossref, Medline, Google Scholar
34 Nguyen HX, Puri A, Banga AK. Methods to simulate rubbing of topical formulation for in vitro skin permeation studies. Int. J. Pharm. 519(1–2), 22–33 (2017).Crossref, Medline, CAS, Google Scholar
35 Eliaz R, Grossman N, Katz S et al. In vitro analysis of bromine chemical burns with use of full-thickness human skin. J. Burn Care Res. 19(1), 18–24 (1998).Crossref, CAS, Google Scholar
36 Kumar V, Banga AK. Modulated iontophoretic delivery of small and large molecules through microchannels. Int. J. Pharm. 434(1–2), 106–114 (2012).Crossref, Medline, CAS, Google Scholar
37 Crichton ML, Archer-Jones C, Meliga S et al. Characterising the material properties at the interface between skin and a skin vaccination microprojection device. Acta Biomater. 36, 186–194 (2016).Crossref, Medline, Google Scholar
38 Larrañeta E, Lutton REM, Brady AJ et al. Microwave-assisted preparation of hydrogel-forming microneedle arrays for transdermal drug delivery applications. Macromol. Mater. Eng. 300(6), 586–595 (2015). • Reports the use of Parafilm M® film to study insertion behavior of microneedles.Crossref, Medline, CAS, Google Scholar
39 Lanke SSS, Kolli CS, Strom JG, Banga AK. Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation. Int. J. Pharm. 365(1–2), 26–33 (2009).Crossref, Medline, CAS, Google Scholar
40 Sivaraman A, Banga AK. Novel in situ forming hydrogel microneedles for transdermal drug delivery. Drug Deliv. Transl. Res. 7(1), 1–11 (2016).Google Scholar
41 Guy RH, Hadgraft J. Rate control in transdermal drug delivery? Int. J. Pharm. 82(3), R1–R6 (1992).Crossref, Google Scholar
42 Berg SL, Cowan KH, Balis FM et al. Pharmacokinetics of taxol and doxorubicin administered alone and in combination by continuous 72-hour infusion. J. Natl Cancer Inst. 86(2), 143–145 (1994).Crossref, Medline, CAS, Google Scholar

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Published online 31 March 2017

Published in print May 2017

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Acknowledgements

The authors would like to extend their gratitude toward Sonalika Arup Bhattaccharjee for her contribution in proof-reading the manuscript.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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