Dual-mode thermo-responsive microneedle liposome patch for adaptive transdermal delivery in postherpetic neuralgia

Postherpetic neuralgia (PHN) presents as persistent background pain accompanied by unpredictable breakthrough episodes. Current topical therapies are poorly suited to this fluctuating pain pattern because they provide limited transdermal penetration and static drug release. Here, we developed a thermo-responsive microneedle platform integrating sustained local lidocaine delivery with externally triggered accelerated release and evaluated its material characteristics, temperature-dependent release behavior, transdermal delivery performance, and in vivo pharmacokinetic behavior. The system consists of a gelatin and poly (ethylene glycol) diacrylate microneedle matrix, lidocaine-loaded liposomes, and a flexible pullulan backing layer. The patch demonstrated adequate mechanical strength for skin insertion, exceeding 0.1 N per needle, achieved an insertion efficiency above 93%, and delivered cargo to a depth of approximately 75 μm near the epidermal-dermal interface. Compared with a conventional topical patch, the microneedle liposome configuration enhanced transdermal permeation and prolonged drug retention in the skin for up to 48 h, enabling both rapid initial delivery and sustained local availability. The system exhibited a dual-mode release profile, with sustained release at physiological skin temperature (33 °C) and accelerated release under mild heating (40 °C), allowing externally triggered control of release kinetics. The flexible backing maintained conformal adhesion under dynamic deformation, and skin evaluation indicated minimal barrier disruption with only mild, transient erythema in human subjects. These findings demonstrate the feasibility of the system as a controlled local delivery platform and support further evaluation of the system in disease-relevant PHN models.