Oil-based Formulation as a Sustained-Released Injection for a Novel Synthetic Peptide

Title:Oil-based Formulation as a Sustained-Released Injection for a Novel Synthetic Peptide

Volume: 16 Issue: 2

Author(s): Guiying Zhang, Jinglai Li, Tao Wang, Lijun Gao and Dongqin Quan

Affiliation:

Keywords: LXT-101, oily formulation, pharmacodynamics, pharmacokinetics, phospholipid-peptide complex, sustained-release.

Abstract: 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.

Cite this article as:

Zhang Guiying, Li Jinglai, Wang Tao, Gao Lijun and Quan Dongqin, Oil-based Formulation as a Sustained-Released Injection for a Novel Synthetic Peptide, Current Pharmaceutical Biotechnology 2015; 16 (2) . https://dx.doi.org/10.2174/1389201015666141111114937