Carvacrol-loaded chitosan-nanoclay microneedles for pathological scars management

Pathological scars represent a major clinical challenge due to excessive collagen deposition and limited therapeutic options. This study aimed to develop and evaluate microneedle (MN) systems based on chitosan-nanoclay nanocomposites (CNNC) incorporating carvacrol (CVR), a natural compound with documented antioxidant activity. CNNC-based MN were fabricated by micromolding under optimized conditions and characterized in terms of morphology, mechanical properties, swelling behaviour, and degradation profile, identifying formulations with robust technological performance. CVR was then loaded into sepiolite to obtain a stable hybrid (CVR@SEP), designed to overcome intrinsic instability and poor solubility of CVR. Loading efficiency was assessed by spectrophotometric and thermogravimetric methods, and antioxidant activity was verified at sub-minimum inhibitory concentrations, in compliance with regulatory requirements for ancillary substances in medical devices. Subsequently, CVR@SEP was incorporated into CNNC-based MN, which retained favorable mechanical performance and demonstrated enhanced antioxidant activity and cytocompatibility, with cell viability exceeding the ISO 10,993-5 threshold. Ex vivo evaluation on human keloid tissue explants revealed a significant reduction in collagen type I deposition compared with untreated controls, with a more pronounced effect observed for the CS_CVR@SEP 1 formulation, containing the highest CVR loading. These findings provide the first evidence that CNNC-based microneedles incorporating CVR@SEP hybrids can modulate collagen accumulation in pathological scars. The work establishes a robust proof-of-concept for a promising medical device strategy, supporting further translational research and in vivo validation.