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.
