Oil-based formulation as a sustained-released injection for a novel synthetic peptide.
In this study, sustained-release of GnRH antagonist peptide LXT-101 was realized through oil formulation, and their releasing characteristics in vitro and in vivo were investigated. In this formulation, the static interaction between cationic charged peptide LXT-101 and the negative charged phospholipid led to the formation of the phospholipid-peptide complex, by which LXT-101 was completely dissolved in oils. This formulation was prepared by mixing an aqueous solution of LXT-101 and empty SUV (small unilamellar liposomes) containing EPC (phosphatidylcholine) and DPPG (1, 2-dipalmitog-sn-glycero-3- phosphoglycerol) at an appropriate ratio, the mixture was subsequently lyophilized, and the resultant was dissolved in the oil to form a clear oily solution containing solubilized peptide LXT-101. With atomic force microscopy combined with Langmuir-Blodgett technology, the morphology of the particles in the oily solution were examined to be oval-shaped and the mean particle size was 150 nm in diameter. In pure water at 37°C, about 70~90 % of LXT-101 was released slowly from the oily formulation over 7 days. An effective sustained suppression of testosterone in beagle dogs could be achieved over a period of seven days with this LXT-101 oily formulation, by i.m. at a dose of 0.2 mg/kg (2 mg/ml). This formulation dramatically improved the bioactivity of LXT-101 compared to its aqueous solution. It was also found that when the concentration of peptide LXT-101 was up to or over 10 mg/ml in aqueous solution, there was no significant difference between the oily formulation and aqueous solution. This fact meant that LXT-101 itself could conduct sustained release in vivo by self-assembly of nanofibers.
Guiying
G
Zhang
Jinglai
J
Li
Tao
T
Wang
Lijun
L
Gao
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing, 100850 China. qdqwzb@163.com.
Dongqin
D
Quan
D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004285:Dogs; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D006727:Hormone Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D007267:Injections; D008081:Liposomes; D008297:Male; D019301:Oleic Acid / Q000737:chemistry; D009842:Oligopeptides / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D010713:Phosphatidylcholines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D013024:Soybean Oil / Q000737:chemistry; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000737:chemistry; D014867:Water / Q000737:chemistry
D003692:Delayed-Action Preparations; D006727:Hormone Antagonists; C514029:LXT-101; D008081:Liposomes; D009842:Oligopeptides; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D014280:Triglycerides; D014867:Water; D019301:Oleic Acid; D007987:Gonadotropin-Releasing Hormone; C022834:miglyol 812; D013739:Testosterone; D013024:Soybean Oil; C030345:1,2-dipalmitoylphosphatidylglycerol