Department of Anesthesiology, Tongji Hospital of Tongji University, Shanghai, China.
Research and Development Department, Shanghai Jingchen Biotechnology Co., Ltd., Shanghai, China.
J Biomater Sci Polym Ed. 2020 Dec;31(17):2252-2267. doi: 10.1080/09205063.2020.1800904. Epub 2020 Aug 4.
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/cm, 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.
为了方便根据患者需求和活动水平的变化调节局部镇痛程度，本研究引入了一种基于聚集体的近红外光激活药物传递系统，以实现按需局部麻醉。通过乳液制备了含有 N-异丙基丙烯酰胺（NIPAM）、甲基丙烯酰基聚乙二醇（APEG）和氧化石墨烯（GOs）的化学交联明胶微凝胶（5-15μm）。在原位自由基聚合后，形成物理网络，产生具有双网络（DN 微凝胶）的微凝胶。DN 微凝胶表现出温敏性。APEG 的共聚导致微凝胶的低临界溶液温度（LCST）升高。DN 微凝胶（NIPAM40+APEG60）的最大体积收缩率随物理交联网络含量的增加而增加。DN 微凝胶还表现出近红外响应能力。在 272 mW/cm 的近红外辐照度下，GOs 含量为 3mg/mL 的 DN 微凝胶在 60s 内温度达到 40°C，体积收缩 14%。DN 微凝胶中的罗哌卡因释放可以通过体外近红外照射有效触发。离心后，形成了一种聚集体微凝胶系统，其中微凝胶紧密堆积，表现出剪切变稀行为，以实现注射。携带罗哌卡因的聚集体 DN 微凝胶被皮下注射到大鼠脚掌。近红外光照射在大鼠脚掌产生按需和重复的渗透麻醉。因此，聚集体 DN 微凝胶系统有利于疼痛管理。
