The administration of therapeutics to peripheral nerve tissue is challenging due to the complexities of peripheral neuroanatomy and the limitations imposed by the blood–nerve barrier (BNB). Therefore, there is a pressing need to enhance delivery effectiveness and implement targeted delivery methods. Recently, erythrocyte-derived exosomes (Exos) have gained widespread attention as biocompatible vehicles for therapeutics in clinical applications. However, engineering targeted Exos for the peripheral nervous system (PNS) is still challenging. This study aims to develop a targeted Exo delivery system specifically designed for presynaptic terminals of peripheral nerve tissue. The clostridium neurotoxin, tetanus toxin-C fragment (TTC), was tethered to the surface of red blood cell (RBC)-derived Exos via a facile and efficient bio-orthogonal click chemistry method without a catalyst. Additionally, Cyanine5 (Cy5), a reactive fluorescent tag, was also conjugated to track Exo movement in both in vitro and in vivo models. Subsequently, Neuro-2a, a mouse neuronal cell line, was treated with dye-labeled Exos with/without TTC in vitro, and the results indicated that TTC-Exos exhibited more efficient accumulation along the soma and axonal circumference, compared to their unmodified counterparts. Further investigation, using a mouse model, revealed that within 72 h of intramuscular administration, engineered TTC-Exos were successfully transported into the neuromuscular junction and sciatic nerve tissues. These results indicated that TTC played a crucial role in the Exo delivery system, improving the affinity to peripheral nerves. These promising results underscore the potential of using targeted Exo carriers to deliver therapeutics for treating peripheral neuropathies.

Traditional Chinese medicine practitioners believed that the maintenance of the health status of any individual or animal is by the harmonious flow of Chi (life force) along a pathway known as the meridian. Interruption or blockage of Chi brings about disorders, pain, and diseases. Acutherapy, therefore, aims at correcting the interruption or blockage of the harmonious flow of Chi along the meridian to restore the healthy condition of the body system. This correction could be accomplished by either acupuncture or acupressure, and are both collectively referred to as acutherapy. Thisform of therapy has been used in both humans and animals for several decades. It is, however, just gaining popularity in the treatment of humans and is still not yet in practice among veterinarians for animal patients in most developing countries like Nigeria. This review, therefore, is aimed at exposing veterinarians from the developing countries to the general application of acutherapy with emphasis on the musculoskeletal system and associated pain where it is most applied. It is highly recommended that the universities, where Veterinary Medicine is studied in developing countries, should endeavor to train their veterinary surgeons in this area and see to how acutherapy can be included in the curriculum. Keywords: Acupressure, Acupuncture, Acutherapy, Musculoskeletal, Veterinary.