ScholarWorks@동국대학교

초록

Purpose Most protein drugs on the market are available in injectable dosage forms due to their metabolic instability and low membrane permeability, demanding more patient-friendly delivery systems for biomacromolecules. Therefore, this study aimed to develop organic clay-based dissolving microneedles for the effective transdermal delivery of protein drugs. Methods The core nanocomplex (AC-Lira) was prepared via electrostatic interaction of aminoclay (AC) with liraglutide (Lira), a glucagon-like peptide-1 receptor agonist. AC-Lira was then mixed with polyvinyl alcohol (PVA) solution and poured into a reverse polydimethylsiloxane mold to fabricate the drug-loaded dissolving microneedles (AC-Lira-PVA-MNs). The in vitro and in vivo effectiveness of AC-Lira-PVA-MNs as the transdermal delivery system of protein drugs were evaluated using various analytical methods. Results AC-Lira-PVA-MNs displayed a uniform pyramidal shape with a tip length of approximately 600 mu m and good mechanical strength (0.83 +/- 0.040 N/needle). Furthermore, the conformational stability of Lira was maintained in AC-Lira-PVA-MNs. At pH 7.0, AC-Lira-PVA-MNs exhibited rapid dissolution, leading to almost complete (> 90%) drug release within 1 h. In-vitro skin insertion studies using pig cadaver skin also confirmed that AC-Lira-PVA-MNs achieved rapid and complete dissolution of needles within 1 h after skin insertion. In rats, the systemic drug exposure after AC-Lira-PVA-MNs administration was comparable to that after subcutaneous (SC) injection. In addition, AC-Lira-PVA-MNs effectively reduced blood glucose level, food intake, and body weight in type 2 diabetic rats to a similar extent to SC injection of Lira. Conclusion The results suggest that organic clay-based dissolving microneedles can be a promising transdermal delivery system for protein drugs.

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