Extended-release drug delivery systems for local anesthetics in veterinary medicine

Abstract

Local anesthetics are commonly used in veterinary clinical practice and are often a part of multimodal analgesic protocols to optimize targeting different aspects of the pain pathway. While effective, standard formulation local anesthetics have relatively short durations of action, offering only a limited amount of postoperative analgesia. Extended-release formulations can help minimize repeat injections, systemic drug exposure and toxicity, and dependence on postoperative rescue analgesia. The two main ways of extending the duration of action of local anesthetics are adjuvants and advanced drug delivery systems. While adjuvants prolong duration through pharmacologic modulation of nociceptive signaling, advanced drug delivery systems physically alter drug release kinetics through sophisticated engineering. This review covers the latter category, which includes multivesicular liposomes, lipid-based nanoparticles, cyclodextrin inclusion complexes, polymeric matrices, and extended-release bupivacaine-meloxicam. Among these formulations, liposomal bupivacaine is the most widely studied and remains the only commercially available product in this review that is approved for veterinary use. The evidence for the efficacy of liposomal bupivacaine remains controversial, with some studies reporting no benefit over standard bupivacaine or placebo and others showing significant benefit. Sustained drug release and favorable safety profiles have been established for lipid-based nanoparticles, cyclodextrin inclusion complexes, polymeric matrices, and extended-release bupivacaine-meloxicam. The clinical utility of these formulations depends on the patient’s needs, species, mode of administration, and procedure. Though early in their clinical development, these strategies to extend the duration of action of local anesthetics show significant promise in the future of veterinary medicine.