The role of PLGA/TPGS nanoparticle on xylazine-ketamine anesthetic activity in male albino rabbits

Abstract

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by food and drug administration (FDA) as harmless adjuvant and is largely used in drug systems delivery. The aim of the study was to use the TPGS polymer as a drug release model to regulate the release of the anesthetic xylazine-ketamine in order to minimize therapeutically reference dose, avoid side effects, and improve efficacy. The study performed on 15 adult local breed male rabbits, divided into 3 groups with same number which injected intramuscularly with single dose of suggested anesthetics. Heart rate, respiratory rate, degree of muscle relaxation, onset of action and stages of anesthesia were evaluated, also induction of anesthesia, surgical anesthesia and recovery time were recorded. Nanoprecipitation technique was optimal method for preparing small particle size as well as reduce dose for therapeutic effect. Small and large dose was showed perfect analgesic and muscle relaxant activity of xylazine-ketamine drugs. Ketamine 30 mg and xylazine 10 mg loaded PLGA showed elevation of conciseness period as well as increase muscle relaxant. Ketamine 30 mg and xylazine 10 mg loaded PLGA reduce heart rate but onset of action delayed when compared with reference drug. The process of nanoprecipitation was ideal for forming small particle sizes and reducing the dosage for therapeutic effects. PLGA loaded with ketamine-xylazine demonstrated improved cycle concentration (walk time) as well as improved muscle relaxant, finally the protocol created an excellent anesthetic combination for induction of general anesthesia.

Evaluation of Fracture Healing After Thyroidectomy in Rabbits Model

“…The surgical site which involved the lateral and medial side of thigh, in addition to the neck in the second group were organized under aseptic technique. Atropine sulfate at a dose of 0.05 mg/kg B.W intramuscularly were injected in the animals as premedication, then after a period of 15 minutes, mixture of 2% xylazine, 20 mg/kg B.W and 5% ketamine, 40 mg/kg B.W was given intramuscularly, the half dose was repeated if it essential (15). The animals were recumbent at lateral side, in control group; a longitudinal skin incision was made on lateral side of the thigh between the great trochanter of femur and the lateral aspect of the patella.…”

Nanoencapsulation of general anaesthetics

“…Ketamine can be dissolved readily in organic solvents, therefore easy to prepare through solvent-antisolvent system, or through salting out preparation. 53,[55][56][57][58][59][60][61] Moreover, it can be easily functionalized via apolipoprotein E (Apo-E) and vitamin E (tocopherol) for active drug targeting. 56,60 Xu et al used PLGA to encapsulate porous silica containing ketamine with larger particle size (50-60 mm) for direct intrathecal administration of ketamine towards the CNS.…”

“…53,[55][56][57][58][59][60][61] Moreover, it can be easily functionalized via apolipoprotein E (Apo-E) and vitamin E (tocopherol) for active drug targeting. 56,60 Xu et al used PLGA to encapsulate porous silica containing ketamine with larger particle size (50-60 mm) for direct intrathecal administration of ketamine towards the CNS. 59 However, the study lacked in vivo assessments to demonstrate the safety of the porous silica on the caudal nerve and the efficiency of analgesia.…”

“…Han et al and Bader et al used Shellac (a water soluble resin used in food industry) and vitamin E to improve homing of the nanoparticle towards the brain. 53,60 As Han et al demonstrated that the PEG-PLGA nanoparticles were well distributed inside the brain, liver and lungs. Similar results were reported for PEG-PLGA coated with Shellac.…”

A Rabbit Clinical Trial of Xylazine-Ketamine vs. Fentanyl-Ketamine for General Anesthesia

“…Several sedatives and tranquilizers are given to animals having minor or major surgery in order to ease discomfort and relax their muscles. In addition to helping to overcome animal tolerance during examination, these drugs are crucial to veterinary practice because they maintain the depth of anesthesia, reduce the number of anesthetic agents needed, and increase margins of safety [5,6].…”