Journal
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
Volume 127, Issue -, Pages 237-243Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejpb.2018.02.014
Keywords
Dermal delivery; Insoluble and high molecular weight drug; Microneedle; Cyclosporin A; Psoriasis; Pharmacokinetic study
Categories
Funding
- biomedical technology development project through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [2017M3A9G2073551]
- Industrial Strategic Technology Development Program - Ministry of Trade, Industry & Energy (MOTIE, Korea) [10067809]
- Korea Evaluation Institute of Industrial Technology (KEIT) [10067809] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Dissolving microneedles (MN) containing cyclosporin A (CyA) were prepared for local delivery of CyA into the dermal layer. The efficacy of using MN to deliver CyA, an insoluble and high molecular weight drug, was observed and compared with oral administration of solubilized CyA. Microneedles containing CyA (CyA MN) were prepared using a closed, low-temperature molding process. The mechanical properties of CyA MN and phase separation were studied regarding the content of CyA. CyA MN were inserted into porcine skin for a predetermined time, and the dissolution and delivered amount of CyA were measured in vitro with an optical microscope and high-performance liquid chromatography (HPLC) analysis of the extracted CyA. A pharmacokinetic study of CyA MN was performed in vivo by administering 10% CyA MN, and the pharmacokinetic profile was compared with that of orally administered CyA. Pyramidal CyA MN (600 pm long, 250 pm wide) were prepared. CyA MN penetrated skin successfully with up to 50% CyA content. When 10% CyA MN were pressed into porcine skin for 60 min, 65% of MN length was dissolved and 34 +/- 6.5 mu g of CyA in MN was delivered into the skin. Under the same conditions with 10% CyA MN administered to rats, CyA MN showed T-max of 8 h, C-max of 15.9 ng/ml, and area under curve (AUC) of 686, compared to T-max of 2 h, C-max of 18.205 ng/ml, and AUC of 254 for oral administration of solubilized CyA. A therapeutic dose of CyA for treatment of psoriasis was delivered via MN into the skin layer without solubilization of CyA. Due to the hydrophobic properties and high molecular weight of CyA, the safety of CyA delivery was improved using dissolving microneedles because the slow systemic absorption and local treatment enabled CyA to remain in the skin for a longer time. Microneedles are an effective method with high bioavailability for local dermal delivery of insoluble drugs.
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