Development of Novel Formulation for Sustained Release of Drug to Prevent Swainsonine-Containing Plants Poisoning in Livestock

SIMPLE SUMMARY: Swainsonine-containing plants are a poisonous plant widely distributed in grasslands around the world, poisoning by it can cause livestock deaths and economic losses to herdsmen. We have developed a sustained-release injection for the prevention of poisoning by swainsonine-containing plants. Compared to other formulation, e.g., powders and pills, injections have the advantage of convenient administration with easy dosage control. The injection uses poloxamer as the sustained-release matrix and can be solidified into a gel at physiological temperature. We have shown that this formulation is safe and can maintain an effective blood drug concentration for up to 5 days, providing a new approach for preventing swainsonine-containing plants poisoning livestock. ABSTRACT: Swainsonine-containing plants contain swainsonine which has been shown to cause neurological signs and pathological changes in farm animals. It causes a large number of livestock poisonings every year resulting in economic losses to the livestock industry. At present, “Jifang E” is used in the prevention of swainsonine-containing plants poisoning livestock, and the preventive effects have been well-documented. However, “Jifang E” is typically administered in drinking water, making it difficult to control the administered dosage, because of feeding difficulties and it may cause certain side effects that are unique to the water-dissolved powder. To overcome these difficulties, we developed a temperature-sensitive gel for injection and the optimal ratio of each formula of sustained-release injection is P407 (24%), P188 (6%), Vitamin C (1%), PEG4000 (0.5%), and “Jifang E” (10%). Our results suggest that novel formulation makes the micellar system more stable and the particles are uniformly dispersed. Colloidal morphological studies showed that each group formed a homogeneous pore structure after gelling, and the structure became more dense with the addition of “Jifang E”. The rheological study shows that “Jifang E” is a pseudoplastic fluid, and the addition of “Jifang E” reduces the viscosity of the formula, which is beneficial to the injection. In vitro and in vivo release rate studies have shown that the effective concentration of “Jifang E” can be maintained for 3 to 5 days. The acute toxicity test in SPF Kunming mice showed that its LD(50) was 828.323 mg/kg, with confidence limits of 676.706–1013.911 mg/kg, which is a safe dosage (LD(50) > 200 mg/kg). There were no observed reactions of muscle irritation or subcutaneous tissue irritation with the dosage used for New Zealand rabbits. In summary, we successfully developed the sustained-release injection formulation of “Jifang E” for the prevention of swainsonine-containing plants poisoning livestock, which provides the basis for subsequent field extension trials and the further study of its detoxification mechanism.