Intradermal delivery of lidocaine hydrochloride using dissolving microneedles: In vitro dermatokinetic test and in vivo anesthetic activity assessment

Lidocaine hydrochloride (LiH) is a widely used local anesthetic administered topically or parenterally. However, passive delivery of LiH through the skin is hindered by its hydrophilicity and discomfort associated with injections. Dissolving microneedles (DMNs) offer a minimally invasive alternative for intradermal delivery. This study developed LiH-loaded DMNs (LiH-DMNs) using a combination of poly(vinylpyrrolidone) K-29/32 (PVP) and hyaluronic acid (HA). LiH-DMNs were evaluated in terms of their mechanical properties, insertion ability, dissolution, drug content, in vitro dermatokinetic tests, and in vivo local anesthetic tests on rats. Nine formulations were prepared, among which DMN-7 (PVP 30%; HA 1.25%) and DMN-8 (PVP 30%; HA 2.5%) showed needle height reduction of <10% and drug content of 97-100%. Both formulations penetrated skin to a depth of approximately 500 μm and fully dissolved within 1 hour In vitro dermatokinetic studies demonstrated higher drug accumulation for DMN-7 (Cmax of 6.75 ± 1.36 μg/mL in the dermis and 7.47 ± 0.97 μg/mL in the epidermis) compared to DMN-8. Consequently, DMN-7 was selected for in vivo evaluation. DMN-7 caused no erythema or edema in irritation studies and produced significant local anesthetic effects in rats. Overall, PVP–HA-based DMNs represent a promising, safe, and effective approach for intradermal delivery of LiH.