Study On Sustained Release IVM PLA/PLGA MS

In this paper, drug of Ivermectin （IVM） was encapsulated in an aliphaticpolyesters consist of poly（lactic acid）（PLA） and copolymers of lactide and glycolidepoly（lactide co glycolide）（PLGA）（Mw15000,20000,25000, abbr. PLA/PLGA1.5,PLA/PLGA2.0, PLA/PLGA2.5） to investigate the sustained release formulation ofIVM loaded microspheres （IVM PLA/PLGA MS） delivery system. The researchdeterminates the drug concentration of microspheres preparation and prescription ofoptimization, in vitro release, acute toxicity experiment, stability andpharmacodynamics, and so on, and it obtains the polymer microspheres characteristicsin achieving extended drug release time.1. IVM PLA/PLGA MS preparation and prescription of optimization.IVM PLA/PLGA MS prescription of optimization by using L₉（3⁴） orthogonalexperiments to prescription factors. Its morphology and particle size distribution wereestimated by scanning electron microscopy （SEM）, and its encapsulation efficiencyand drug loading efficiency were assessed by High performance liquidchromatography （HPLC）. Results showed that IVM elution was monitored byabsorbance at wavelength of245nm, and the standard curve for IVM with a goodlinear relationship （r=0.9992） in the range of5¹00g/mL. RSD of the recoverydetermination was99.01%, and the precision determination for Inter day andIntra day was lesss than5%. The IVM PLA/PLGA MS made from the multipleemulsion solvent evaporation technique were ivory, smooth surfaces, spherical andwithout any accretion. For example, for one of IVM PLA/PLGA MS, PLA/PLGA2.0,the encapsulation efficiency was91.20%and90.79%, and the drug loading efficiencywas29.34%and30.11%. Moreover, the recovery efficiency was94.52%and95.37%,and the mean diameter was8.42±0.16m and10.23±0.31m, respectively.2. In vitro release and stability evaluation of IVM PLA/PLGA MS. In drugrelease in vitro experiment, the microspheres were suspended in optimized PBS buffer,and the suspension was poured in a dialysis bag and also analyzed by HPLC at last.The stability of IVM PLA/PLGA MS was evaluated by light stability experiments,thermal stress experiments, low temperature test and long term experiment.Consequently, we obtain an enough drug release time for potentially optimized extended efficacy. IVM which is PLA/PLGA microspheres loaded has anaccumulative release in vitro less than70%in18days. The light stability experimentsand low temperature test dose not affect the microshperes, which RSD was about1%,but the thermal stress experiments greatly infuluences the microspheres, and the RSDwas about5%.3. Security evaluation of IVM PLA/PLGA MS. The security evaluation ofIVM PLA/PLGA MS was analyzed by acute toxicity experiment, muscle stimulationexperiment, vascular stimulation tests and hemolytic test. The results showed thatIVM PLA/PLGA MS was nontoxic. LD₅₀of IVM PLA/PLGA MS on mouse was259.90mg/kg, and LD₅₀95%was221.87³04.44mg/kg. The result of musclestimulation experiment, vascular stimulation tests and hemolytic test showed thatIVM PLA/PLGA MS was low irritative and consistentwith clinical medication.4. The pharmacodynamics evaluation of IVM PLA/PLGA MS on ou la sheep. Byusing4mg/kg IVM PLA/PLGA MS, the effects of curing acarus on ou la sheep wereevaluated. Results show that cure rates of4mg/kg IVM PLA/PLGA MS weresignificantly higher than that of conventional0.4mg/kg IVM. The ovum decrementrate of Ou la sheep were75.90%and80.42%after93days of premedicationIVM PLA/PLGA MS injection, but conventional IVM treatment was only18.58%.