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. Physicochemical and biological possessions of TPGS provide many advantages for its usage in drug delivery, such as high bio-compatibility, increased drug solubility, improved drug penetration and selective anti-tumor action. 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. Group 1 injected with ketamine and xylazine. Group 2 injected with ketamine and xylazine as same dose of group 1 loaded by PLGA-TPGS. Group 3 injected with Ketamine and xylazine loaded by PLGA-TPGS with half dose of Group 1 and 2. The following physiological parameters were evaluated: heart rate, respiratory rate, degree of muscle relaxation, onset of action and stages of anesthesia before administration the drug at time zero then at 10, 30 and 60 minutes after drug administration, 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.