title: Design and optimization of thermosensitive nanoemulsion hydrogel for sustained-release of praziquantel.
abstract: OBJECTIVE
  This work aimed to develop an alternative sustained-release thermosensitive praziquantel-loaded nanoemulsion (PZQ-NE) hydrogel for better schistosomiasis treatment.
  
  
  CONCLUSIONS
  PZQ-NE-dispersed chitosan/glycerol 2-phosphate disodium/HPMC (NE/CS/β-GP/HMPC) hydrogel was successfully prepared to improve bioavailability of PZQ.
  
  
  METHODS
  Solubility tests and pseudo-ternary phase diagrams were applied to screen optimal oils, surfactants and co-surfactants of NE. The hydrogels were characterized for gelling time, surface exudates, rheological properties and in vitro drug release. Formulation optimization of NE/CS/β-GP/HMPC hydrogel was conducted by Box-Behnken experimental design combined with response surface methodology. In vitro cytotoxicity of hydrogel was studied by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide method. The sustained-release property of PZQ in NE and optimized hydrogel was evaluated by pharmacokinetic study in rabbits.
  
  
  RESULTS
  The formulation of PZQ-NE consisted of mass ratio of 12.5% capryol 90 containing PZQ (160 mg/g), 40% cremophor RH 40/tween 20 and transcutol HP (S/CoS = 2:1), 47.5% deionized water. PZQ releasing from NE/CS/β-GP/HMPC hydrogels was best fitted to Higuchi model and governed by diffusion. Rheological investigation evidenced the themosensitive gelation of different hydrogel systems and their gel-like character at 37 °C. The optimized hydrogel formulation consisted of HPMC solution (103.69 mg/g), 3.03% (w/v) chitosan and 14.1% (w/v) β-GP showed no cytotoxicity when the addition of NE was no more than 100 mg/g. Pharmacokinetic parameters indicated that NE/CS/β-GP/HMPC hydrogel can significantly slow down drug elimination, prolong mean residence time and improve bioavailability of PZQ.
  
  
  CONCLUSIONS
  NE/CS/β-GP/HMPC hydrogel possessed sustained-release property and could be an alternative antischistosomal drug delivery system with improved therapeutic effect.
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Zhaotong
authors.initials: Z
authors.lastname: Cong
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Yanbin
authors.initials: Y
authors.lastname: Shi
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Peng
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Bei
authors.initials: B
authors.lastname: Wei
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Jincheng
authors.initials: J
authors.lastname: Li
authors.affiliation: b CAAS , Institute of Lanzhou Husbandry and Animal Pharmaceutics , Lanzhou , P.R. China.
authors.forename: Jianyong
authors.initials: J
authors.lastname: Li
authors.affiliation: a School of Pharmacy, Lanzhou University , Lanzhou , P.R. China.
authors.forename: Jiazhong
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D048271:Chitosan / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D004655:Emulsions / Q000737:chemistry*; D005260:Female; D005994:Glycerophosphates / Q000737:chemistry; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D053758:Nanoparticles / Q000737:chemistry*; D011223:Praziquantel / Q000737:chemistry* / Q000378:metabolism; D011817:Rabbits; D012212:Rheology; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013696:Temperature
chemical_list: D003692:Delayed-Action Preparations; D004655:Emulsions; D005994:Glycerophosphates; D012996:Solutions; D013501:Surface-Active Agents; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011223:Praziquantel; D048271:Chitosan
keywords: Box–Behnken design; Praziquantel; cytotoxicity; hydrogel; nanoemulsion; pharmacokinetics