Effects Of Abendazole Sulfoxide-loaded Thermo-sensitive Hydrogel On Helminths

Objective: To explore the anti-helminthes efficacy of abendazole sulfoxide-loaded thermo-sensitive hydrogel(ABZSO/ PLGA-PEGPLGA).Methods: ABZSO/PLGA-PEG-PLGA was prepared by the solvent evaporation method,and its phase diagram transition behavior was investigated.ABZSO/PLGA-PEG-PLGA was proved by FT-IR,1H NMR.The in vitro behaviors of the hydrogel were studied with membraneless models.The relationship between In vitro erosion and drug release,drug release kinetics of ABZSO/PLGA-PEG-PLGA was also studied by Origin 7.5.The concentration-time curve of ABZSO/PLGA-PEG-PLGA in the plasma of rats was obtained,and the pharmacokinetic parameters were analysed by DAS 2.0;the lethality of ABZSO/PLGA-PEG-PLGA to the nematode Caenorhabditis elegans was investigated so as to explore its antihelminthes efficacy preliminarily.The in vivo and in vitro anti-alveolar hydatid cysts efficacies of ABZSO/PLGA-PEG-PLGA were studied to validate its effects on helminthes further.Firstly,the protoscoleces incubated in vitro with ABZSO/PLGA-PEG-PLGA,and the viable protoscoleces were counted.The morphological changes of the alveolar hydatid cysts or protoscoleces in each group were observed by scanning electron microscop(SEM).In vivo experiment,after the rats infected with alveolar hydatid cysts having been treated,the sizes of the alveolar hydatid cysts were checked to estimate the hydrogel's anti-alveolar hydatid cysts efficacy.Results: The results indicated that ABZSO/PLGA-PEG-PLGA was a transparent homogeneous solution,could easily pass the 25-gauge needle at 25?,and the gel state,precipitate state of ABZSO/PLGA-PEG-PLGA were showed,additionally,the results of transition temperature showed that its sol-gel transition temperature was 30?and gel-sol transition temperature was 37?.The results of FT-IR spectra and 1HNMR spectra showed that the structure of ABZSO and PLGA-PEG-PLGA was not changed;The results of in vitro release showed the cumulative release of the ABZSO was only 80.3% by the 6th day,and the cumulative drug release in vitro was plotted against erosion amount,got a straight line(R2 =0.999),the results of in vitro drug release kinetics showed that the release of ABZSO/PLGA-PEG-PLGA was mainly controlled by the Higuchi model(R2=0.992).The pharmacokine-tics indicated that the maximum concentration of ABZSO/PLGA-PEGPLGA group(178.09 ng/ml)was higher than that of ABZSO group(131.98 ng/ml);In the preliminary test of the anti-helminthes efficacy of ABZSO/ PLGA-PEG-PLGA showed that the lethality of ABZSO/PLGA-PEG-PLGA group to the Caenorhabditis elegans was remarkably higher than the ABZSO group.The anti-helminthes efficacy was further studied by the study of anti-alveolar hydatid cysts efficacy of ABZSO/PLGA-PEG-PLGA in vitro and in vivo.When the alveolar hydatid cysts incubated with different drug groups at 18 d,the percentage of viable protoscoleces in ABZSO/ PLGA-PEG-PLGA(40?g/ml)group was significantly lower than that of ABZSO(40?g/ml)group.The results of SEM showed that theprotoscoleces in ABZSO/PLGA-PEG-PLGA(80?g/ml)group were seriously damaged.The in vivo study demonstrated the anti-alveolar hydatid cysts efficacy of ABZSO/PLGA-PEG-PLGA(4mg/ml)group was better than those in other groups.Therefore,The anti-alveolar hydatid cysts efficacy of ABZSO/ PLGA-PEG-PLGA was evident.Conclusion: The injectable abendazole sulfoxide-loaded thermosensitive hydrogel was successfully manufactured,and it was proved that the ABZSO was successfully loaded into the PLGA-PEG-PLGA and the structure of ABZSO,PLGA-PEG-PLGA was not changed.The study of pharmacokinetics and pharmacodynamics indicated that ABZSO/PLGAPEG-PLGA was evidently superior to ABZSO,and the ABZSO/PLGAPEG-PLGA has the anti-helminthes efficacy to the Caenorhabditis elegans.In addition,the evident efficacy of anti-helminthes was further proved by the study of anti-alveolar hydatid cysts efficacy of ABZSO/PLGAPEG-PLGA in vitro and in vivo.