Organic clay-based fast dissolving microneedles for efficient transdermal delivery of therapeutic proteins

Abstract

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.