title: Multivesicular liposome (MVL) sustained delivery of a novel synthetic cationic GnRH antagonist for prostate cancer treatment.
abstract: OBJECTIVE
  Multivesicular liposomes (MVLs) are often used as an appropriate carrier for delivering peptides due to high drug loading, relative stability and extended-release behaviour. However, when cationic amphipathic peptides are involved, some challenges may be encountered, including instability of multiple emulsions due to interaction between peptides and lipid membranes (electrostatic and hydrophobic interaction). LXT-101, a cationic amphipathic peptide, is a novel antagonist of gonadotropin-releasing hormone (GnRH) for prostate cancer treatment. The purpose of the current research was to explore simple methods of determining the interaction between peptide and lipid bilayer and to prepare MVLs of LXT-101 (DepoLXT-101) by the modified DepoFoam technique.
  
  
  METHODS
  The anionic surfactants were added in the process of DepoLXT-101 preparation in order to minimize the effect of instability resulting from cationic peptides.
  
  
  RESULTS
  DepoLXT-101 was obtained with good efficiency and reproduction. The integrity of encapsulated peptide was maintained as shown by RP-HPLC. DepoLXT-101 particles were characterized by morphology and particle size distribution and in-vitro release was also investigated. The release behaviour in vitro in medium of sodium chloride at 37°C showed that 70-90% of LXT-101 was released slowly from MVLparticles over 11 days. According to the fitting results of Ritgar-Pepps model, the in-vitro release of DepoLXT-101 was mainly governed by Fick's diffusion.
  
  
  CONCLUSIONS
  The data obtained from in-vivo study indicated that a sustained anticancer effect can be achieved over a 7-day period with subcutaneous administration of DepoLXT-101 in rats.
authors.affiliation: Beijing Institute of Pharmacology and Toxicology, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Lijun
authors.initials: L
authors.lastname: Gao
authors.forename: Dongqin
authors.initials: D
authors.lastname: Quan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D002412:Cations; D003692:Delayed-Action Preparations; D004058:Diffusion; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D004355:Drug Stability; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006727:Hormone Antagonists / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D010316:Particle Size; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry; D053835:Unilamellar Liposomes
chemical_list: D000970:Antineoplastic Agents; D002412:Cations; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006727:Hormone Antagonists; C514029:LXT-101; D009842:Oligopeptides; D013501:Surface-Active Agents; D053835:Unilamellar Liposomes; D007987:Gonadotropin-Releasing Hormone