title: Schistosoma japonicum: treatment of different developmental stages in mice with long-acting praziquantel implants.
abstract: This paper reports the effective treatment of Schistosoma japonicum in a mouse model with long-acting praziquantel (PZQ)-loaded poly(ε-caprolactone) implants. The implants yielded stable, high plasma PZQ concentrations ranging 100-1600 ng/mL during the 40-day investigation period. For assessment of efficacy, the implants were implanted into mice immediately after infection and at 1, 2, 3 and 4 weeks after infection to treat the schistosomes at different developmental stages. All the mice were sacrificed at 6 weeks after infection for worm and egg recovery, worm morphology examination, and histopathological analysis of implantation site tissues. The worm burdens, egg burdens, and numbers of miracidia hatched from the retrieved eggs for all the implant-treated groups (except groups T2-A, T4 and T5) were reduced by 100% when compared with the control group. From groups T2-A, T4 and T5, some schistosome debris was recovered. Eggs were found in only group T5 for which the time between infection and implantation was 4 weeks, which enabled the maturation of juvenile female schistosomes into adult ones that lay eggs. Histopathological observations of implantation tissue showed no evidence of granulomatous foreign-body or lymphoid cell aggregation, demonstrating good biocompatibility of the PZQ implants. These results demonstrate that the long-acting PZQ implants can kill schistosomes at any developmental stages and attenuate/avoid the associated liver damage.
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.forename: Shengrong
authors.initials: S
authors.lastname: Guo
authors.forename: Chuangang
authors.initials: C
authors.lastname: Zhu
authors.forename: Haojun
authors.initials: H
authors.lastname: Rong
authors.forename: Dongwei
authors.initials: D
authors.lastname: Guo
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Lin
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004343:Drug Implants; D005260:Female; D008018:Life Cycle Stages / Q000187:drug effects; D008099:Liver / Q000469:parasitology; D008297:Male; D051379:Mice; D010270:Parasite Egg Count; D011223:Praziquantel / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011897:Random Allocation; D012549:Schistosoma japonicum / Q000187:drug effects* / Q000254:growth & development; D012554:Schistosomiasis japonica / Q000188:drug therapy*
chemical_list: D000871:Anthelmintics; D003692:Delayed-Action Preparations; D004343:Drug Implants; D011223:Praziquantel