Near-infrared triggered on-demand local anesthesia using a jammed microgels system

Abstract

To conveniently modulate the degree of local analgesia in response to changes in patients’ needs and level of activity, a NIR-activated drug delivery system based on jammed microgels was introduced in the present study to realize on-demand local anesthesia. Chemically cross-linked gelatin microgels (5–15 μm) containing N-isopropylacrylamide (NIPAM), methylallyl polyethylene glycol (APEG) and graphene oxide (GOs) were fabricated through emulsion. After the in situ free radical polymerization, the physical network was formed, producing microgels with double networks (DN microgels). The DN microgels exhibited thermosensitive properties. The copolymerization of APEG resulted in the increase of lower critical solution temperature (LCST) of microgels. The maximum volume shrinkage ratio of DN microgels (NIPAM40 + APEG60) increased with the increase of the content of physical cross-linking network. The DN microgels also exhibited NIR-responsive ability. Under the NIR irradiance of 272 mW/cm2, the temperature of DN microgels with 3 mg/mL GOs reached 40 °C within 60 s, resulting in the volume shrinkage of 14%. Ropivacaine release from DN microgels could be effectively triggered by NIR irradiation in vitro. After centrifugation, a jammed microgels system was produced where microgels packed densely, displaying shear-thinning behavior for achieving injection. The jammed DN microgels carrying ropivacaine were injected subcutaneously into rat footpad. NIR irradiation produced on-demand and repeated infiltration anesthesia in the rat footpad. The jammed DN microgels system thus was beneficial in the management of pain.