Control Release Anesthetics to Enable an Integrated Anesthetic-mesenchymal Stromal Cell Therapeutic.

Abstract

While general anesthetics control pain via consciousness regulation, local anesthetics (LAs) act by decreasing sensation in the localized area of administration by blocking nerve transmission to pain centers. Perioperative intra-articular administration of LAs is a commonly employed practice in orthopedic procedures to minimize patient surgical and post-surgical pain and discomfort. LAs are also co-administered with cellular mesenchymal stromal cell (MSC) therapies for a variety of tissue regenerative and inflammatory applications including osteoarthritis (OA) treatment; however, LAs can affect MSC viability and function. Therefore, finding an improved method to co-administer LAs with cells has become critically important. We have developed a sustained release LA delivery model that could enable the co-administration of LAs and MSCs. Encapsulation of liposomes within an alginate matrix leads to sustained release of bupivacaine as compared to bupivacaine-containing liposomes alone. Furthermore, drug release is maintained for a minimum of 4 days and the alginate-liposome capsules mitigated the adverse effects of bupivacaine on MSC viability.