title: Characterization and in vivo evaluation of novel lipid-chlorambucil nanospheres prepared using a mixture of emulsifiers for parenteral administration.
abstract: OBJECTIVE
  The purpose of the study was to develop and evaluate different lipid-based formulations for parenteral administration, as potential novel carrier systems for lipophilic drugs, and to turn an unstable drug such as chlorambucil into a useful one.
  
  
  METHODS
  A two-stage, high-pressure homogenizer was used to yield a very fine monodispersed lipid nanosphere. The strategy of combining egg yolk phospholipid and nonionic emulsifier (Lutrol F 68 and Tween 80) as an emulsifier mixture was adopted to increase safety and tolerance. The final lipid nanospheres, in a lipophilic mixture consisting of three components, monostearin, medium-chain triglycerides and soya oil, were evaluated for physicochemical properties, such as particle size, surface morphology, drug-entrapment efficiency, drug-loading capacity, lyophilization and in vivo drug-release behavior.
  
  
  RESULTS
  A monodispersed lipid nanosphere with a mean particle size ranging from 90 to 150 nm was achieved. The optimized injectable cryoprotectants for lipid nanosphere were sucrose (7.5%) and mannitol (7.5%), which can stabilize the particle size (LD50) at approximately 129 nm after reconstitution. The results show that the formulation can effectively administer anticancer drugs and thus improve patient quality of life.
  
  
  CONCLUSIONS
  The novel lipid nanosphere complex developed is a useful anticancer drug delivery vehicle for parenteral administration. The formulation strategy has the potential for the development of further methods of drug delivery for a wide variety of anticancer drugs.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Shufang
authors.initials: S
authors.lastname: Nie
authors.forename: Xinggang
authors.initials: X
authors.lastname: Yang
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.forename: Hongtao
authors.initials: H
authors.lastname: Xu
authors.forename: Liangyuan
authors.initials: L
authors.lastname: Zheng
authors.forename: Weisan
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002152:Calorimetry, Differential Scanning; D002699:Chlorambucil / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D003451:Cryoprotective Agents / Q000737:chemistry; D016503:Drug Delivery Systems; D004355:Drug Stability; D045703:Emulsifying Agents / Q000008:administration & dosage / Q000737:chemistry*; D005612:Freeze Drying; D005989:Glycerides / Q000008:administration & dosage / Q000737:chemistry*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D054118:Nanospheres / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D051381:Rats; D012995:Solubility
chemical_list: D003451:Cryoprotective Agents; D045703:Emulsifying Agents; D005989:Glycerides; D002699:Chlorambucil