title: Development of a biocompatible creatinine-based niosomal delivery system for enhanced oral bioavailability of clarithromycin.
abstract: BACKGROUND
  Nonionic surfactant vesicles have gained increasing scientific attention for hydrophobic drugs delivery due to their biocompatibility, stability and low cost.
  
  
  OBJECTIVE
  The aim of the present study was to synthesize and evaluate a novel creatinine-based nonionic surfactant in terms of its ability to generate biocompatible niosomal system for the delivery of Clarithromycin.
  
  
  METHODS
  The surfactant was synthesized by reacting creatinine with lauroyl chloride followed by characterization using1HNMR and MS. The drug-loaded niosomal vesicles of the surfactant were characterized for drug encapsulation efficiency (EE) using LC-MS, vesicle size using dynamic light scattering (DLS) and vesicle shape using atomic force microscopy (AFM). The surfactant was also investigated for blood hemolysis, in vitro cytotoxicity against different cell lines and in vivo acute toxicity in mice. Furthermore, the in vivo bioavailability of Clarithromycin encapsulated in the novel niosomal formulation was investigated using rabbits and quantified through validated LC-MS/MS method.
  
  
  CONCLUSIONS
  Findings showed that vesicles were able to entrap up to 67.82 ± 1.27% of the drug, and were rounded in shape with a size around 202.73 ± 5.30 nm and low polydispersity. The surfactant caused negligible blood hemolysis, very low cytotoxicity and was found to be safe up to 2500 mg/kg body weight using mice. The niosomal formulation showed twofold enhanced oral bioavailability of Clarithromycin as compared to commercial formulations of the drug.
  
  
  CONCLUSIONS
  The study has shown that the creatinine-based niosomes developed in our laboratory were biocompatible, safe and increased the oral bioavailability of the model hydrophobic Clarithromycin using experimental animals.
authors.affiliation: a Department of Pharmacy , University of Malakand , Chakdara, Khyber Pakhtoonkhwa , Pakistan.
authors.forename: Shafi
authors.initials: S
authors.lastname: Ullah
authors.affiliation: b HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University , Karachi , Pakistan , and.
authors.forename: Muhammad Raza
authors.initials: MR
authors.lastname: Shah
authors.affiliation: a Department of Pharmacy , University of Malakand , Chakdara, Khyber Pakhtoonkhwa , Pakistan.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shoaib
authors.affiliation: a Department of Pharmacy , University of Malakand , Chakdara, Khyber Pakhtoonkhwa , Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Imran
authors.affiliation: c College of Pharmacy, Qatar University , Doha , Qatar.
authors.forename: Abdelbary M A
authors.initials: AM
authors.lastname: Elhissi
authors.affiliation: b HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University , Karachi , Pakistan , and.
authors.forename: Farid
authors.initials: F
authors.lastname: Ahmad
authors.affiliation: b HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, Karachi University , Karachi , Pakistan , and.
authors.forename: Imdad
authors.initials: I
authors.lastname: Ali
authors.affiliation: a Department of Pharmacy , University of Malakand , Chakdara, Khyber Pakhtoonkhwa , Pakistan.
authors.forename: Syed Wadood Ali
authors.initials: SW
authors.lastname: Shah
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry*; D001682:Biological Availability; D002460:Cell Line; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D017291:Clarithromycin / Q000737:chemistry* / Q000378:metabolism*; D003404:Creatinine / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D004355:Drug Stability; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008081:Liposomes / Q000737:chemistry*; D051379:Mice; D041681:NIH 3T3 Cells; D010316:Particle Size; D013501:Surface-Active Agents / Q000737:chemistry
chemical_list: D001672:Biocompatible Materials; D008081:Liposomes; D013501:Surface-Active Agents; D003404:Creatinine; D017291:Clarithromycin
keywords: Bioavailability; LC-MS/MS; biocompatibility; niosomal drug delivery; surfactant