Transdermal Delivery of Polymeric Nanoparticles Containing Aconite Root for the Treatment of Chemotherapy-Induced Peripheral Neuropathy

Chemotherapy-induced peripheral neuropathy (CIPN) poses challenges like pain and numbness, necessitating innovative treatments due to current limitations. Conventional approaches, relying on pain relief medications and dose adjustments, fall short in addressing neurotoxicity, resulting in inadequate pain relief and undesired effects. Aconite root (AR), a medicinal herb withcenturies of use against various diseases, contains a compound named Aconine, which alleviates pain by blocking specific neural channels. However, AR also contains Aconitine, a toxic substance hydrolyzed into nontoxic Aconine through heating. Herein, hyaluronate-poly(lactic-co-glycolic acid) nanoparticles (HA-PLGA/AR NPs) encapsulating Aconine are fabricated, enabling controlled release, protection, and transdermal delivery, enhancing therapeutic outcomes. High-performance liquid chromatography identifies optimal Aconine content after 48 h of AR boiling, with minimal neural toxicity confirmed. Characterization via transmission electron microscopy, dynamic light scattering, and in vitro assays demonstrates superior drug release by HA-PLGA/AR NPs, establishing effective transdermal Aconine delivery. In an in vitro CIPN model with paclitaxel (PTX)-treated PC12 cells, HA-PLGA/AR NPs stimulate enhanced neurite growth, validating their localized analgesic impact on CIPN and suggesting potential symptom alleviation. Taken together, HA-PLGA/AR NPs offer a promising strategy for controlled transdermal Aconine delivery, potentially alleviating CIPN and addressing various neuropathies and diseases. This study addresses chemotherapy-induced peripheral neuropathy (CIPN) using hyaluronic acid-poly(lactic-co-glycolic acid) nanoparticles (HA-PLGA NPs) loaded with Aconite Root extract. Through transdermal delivery, these NPs target peripheral nerves, utilizing analgesic properties of Aconine from the extract. The NPs interact with ion channels, diminishing pain signal transmission, validated by increased neurite growth in paclitaxel (PTX)-treated PC12 cells. This approach presents a promising strategy for treating CIPN.image (c) 2024 WILEY-VCH GmbH