title: Design and evaluation of injectable niclosamide nanocrystals prepared by wet media milling technique.
abstract: Niclosamide is an anthelmintic drug that also demonstrates great potential in fighting against cancers. However, parenteral delivery of niclosamide is challenged due to its insoluble property. This study aimed to develop an injectable formulation for niclosamide using nanocrystals. Niclosamide nanocrystals were prepared by wet media milling technique and characterized by electronic microscopes, differential scanning calorimetry, powder X-ray diffractometry and drug release, etc. The resulting nanocrystals using Tween 80 as the stabilizer were approximately 235 nm in particle size and showed a satisfactory stability. Pharmacokinetic studies revealed that there was no significant difference in plasma concentration-time profiles between nanocrystals and the control formulation (i.e. drug solution). By contrast, a significant difference in tissue distribution was observed at 2 h. Further, niclosamide nanocrystals presented a comparable antitumor effect to the drug solution against EC9076 cell line. We concluded that the nanocrystal formulation with solution-like behaviors should be a promising choice for intravenous delivery of niclosamide.
authors.affiliation: a Division of Pharmaceutics , College of Pharmacy, Jinan University , Guangzhou , China.
authors.forename: Yanghuan
authors.initials: Y
authors.lastname: Ye
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
authors.forename: Tianpeng
authors.initials: T
authors.lastname: Zhang
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Baojian
authors.initials: B
authors.lastname: Wu
mesh_terms: D000818:Animals; D000871:Anthelmintics / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D002152:Calorimetry, Differential Scanning; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D053758:Nanoparticles; D009534:Niclosamide / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013997:Time Factors; D014018:Tissue Distribution
chemical_list: D000871:Anthelmintics; D000970:Antineoplastic Agents; D011136:Polysorbates; D009534:Niclosamide
keywords: Antitumor activity; intravenous delivery; nanocrystals; niclosamide; pharmacokinetics; tissue distribution