(150b) Using Melanin Nanoparticles As Drug Carriers for Long-Lasting Nerve Blocks

Local anesthesia is commonly used for managing post-operative pain that can last up to 5-7 days, as well as chronic pain lasting over 12 weeks. While conventional amino-amide and amino-ester local anesthetics are effective, their typical nerve block or infiltration duration is relatively short, around 2-3 hours, due to rapid clearance. The aim of this research is to develop a local anesthetic preparation that can provide prolonged duration of local anesthesia from a single perineural injection, with minimal local or systemic side effects. To achieve this, we propose to use melanin nanoparticles (MNPs) as delivery systems for local anesthetics. Melanin is known for its exceptional biocompatibility, biodegradability, and abundance in pigmented human tissue. Melanin's inherent chemical structure and hydrophobic nature enable the encapsulation of drugs with aromatic rings through π-π interactions and hydrophobic interactions. These properties make MNPs an ideal delivery platform for amino-amide and amino-ester local anesthetics.

We have developed ultrasmall-sized MNPs (~4 nm) and loaded them with local anesthetics, such as bupivacaine, lidocaine, and capsaicin. In vitro, we will characterize the particle size, surface charge, and morphology using DLS and TEM. We will also determine the drug loading capacity, drug encapsulation efficiency, and release profile using a UV spectrophotometer. Additionally, we will evaluate the sciatic nerve block and systemic toxicity of the local anesthetic-loaded MNPs in a rat sciatic nerve model, comparing it with local anesthetic alone. The expected outcome of this project is a local anesthetic formulation that is even safer and provides longer-lasting nerve blocks than can be achieved with the currently used rapidly cleared lipophilic anesthetics.