Fabrication of Tip-Dissolving Microneedles for Transdermal Drug Delivery of Meloxicam
Dissolving microneedles (MNs) offered a simple, minimally invasive method for meloxicam (MX) delivery to the skin. However, the fabrication of dissolving MNs still faced some challenges, such as significant time consumption, loss of drug activity, and difficulty in regulating MN drug loading. To address these issues, we developed the tip-dissolving (TD) MNs. Several kinds of drugs were encapsulated successfully, and the quantity of MX ranged from 37.23 ± 8.40 to 332.53 ± 13.37 μg was precisely controlled. The effects of fabrication process on biomacromolecules stability were studied, and it was found that tyrosinase kept 90.4% activity during the fabrication process. The whole process for the fabrication of MNs only takes approximately 1 h. In order to further evaluate the potential of the TD MNs, MX TD MNs were prepared for in vitro release experiments, in vivo release experiments, safety evaluation, pharmacokinetic studies, and pharmacodynamic studies. The results demonstrated that MX TD MNs offered several advantages, including rapid release of the encapsulated drug (91.72% within 30 min), efficient drug delivery to skin (79.18%), no obvious skin irritation, decent relative bioavailability (122.3%), and strong anti-inflammatory and analgesic effects. Based on these results, we envisage that the TD MNs have promising potential for transdermal drug delivery of MX.
KEY WORDSmeloxicam microneedles transdermal drug delivery pharmacokinetics pharmacodynamics
This work was supported by the Natural Science Foundation of Fujian Province (Grant No. 2015J05167), the Education Department of Fujian Province (Grant No. JZ160470), the Program for Distinguished Young Talents in Fujian Province University, Putian University (Grant Nos. 2014052 and 2015075), and Training Program of Innovation and Entrepreneurship for Undergraduates (Grant Nos. 201711498004, 201711498055, and 201711498070).
- 4.Distel M, Mueller C, Bluhmki E, Fries J. Safety of meloxicam: a global analysis of clinical trials. Br J Rheumatol. 1996;35(Suppl 1):68–77. https://doi.org/10.1093/rheumatology/35.suppl_1.68.CrossRefPubMedGoogle Scholar
- 5.Lanes SF, Rodrigeuz LA, Hwangg E. Baseline risk of gastrointestinal disorders among new users of meloxicam, ibuprofen, diclofenac, naproxen and indomethacin. Pharmacoepidemiology and drug safety. 2000;9(2):113–7. doi: https://doi.org/10.1002/(SICI)1099-1557(200003/04)9:2<113::AID-PDS478>3.0.CO;2–2.
- 9.YC A, Choi JK, Choi YK, Ki HM, Bae JHA. Novel transdermal patch incorporating meloxicam: in vitro and in vivo characterization. Int J Pharm. 2010;385(385):12–9.Google Scholar
- 11.Pathan I, Mangle M, Bairagi S. Design and characterization of nanoemulsion for transdermal delivery of meloxicam. Analytical. Chem Lett. 2016:286–95.Google Scholar
- 13.Duangjit S, Obata Y, Sano H, Onuki Y, Opanasopit P, Ngawhirunpat T, et al. Comparative study of novel ultradeformable liposomes: menthosomes, transfersomes and liposomes for enhancing skin permeation of meloxicam. Biol Pharm Bull. 2014;37(2):239–47. https://doi.org/10.1248/bpb.b13-00576.CrossRefPubMedGoogle Scholar
- 19.Donnelly RF, Garland MJ, Morrow DIJ, Migalska K, Singh TRR, Majithiya R, et al. Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution. J Control Release. 2010;147(3):333–41. https://doi.org/10.1016/j.jconrel.2010.08.008.CrossRefPubMedGoogle Scholar
- 32.Chang J-S, P-C W, Huang Y-B, Tsai Y-H. In-vitro evaluation of meloxicam permeation using response surface methodology. J Food Drug Anal. 2006;14(3)Google Scholar
- 39.Hong X, Wei L, Wu F, Wu Z, Chen L, Liu Z, et al. Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Des Dev Therap. 2013;7(3):945–52.Google Scholar
- 40.Klein TE, Altman RB, Eriksson N, Gage BF, Kimmel SE, Lee MT, et al. Estimation of the warfarin dose with clinical and pharmacogenetic data. N Engl J Med. 2009;360(16):1613.Google Scholar
- 41.Cohn D, Salomon AH. Designing biodegradable multiblock PCL/PLA thermoplastic elastomers. Biomaterials. 2005;26(15):2297–305. https://doi.org/10.1016/j.biomaterials.2004.07.052.CrossRefPubMedGoogle Scholar