Development of thermosensitive liposome-containing in-situ gel systems for intranasal administration of thiocolchicoside and in vivo evaluation in a rabbit model.

Abstract

Aim: Thiocolchicoside (THC) is a drug under the category of BCS III. Due to its high molecular weight, it has poor oral bioavailability and low skin permeability. This study aims to find an alternative delivery method for THC that enhances its bioavailability through nasal application approach. In situ gels containing plain or liposomal THC with different combinations of Pluronic® F127 and PEG 400 were prepared.

Method: Liposome formulations were prepared using the thin film hydration method and tested for their characterization such as for drug content, particle size, and zeta potential. In vivo pharmacokinetic parameters of formulations such as C_max, T_max, and AUC were tested on the rabbit model. The formulations were also scrutinized for their cell viability properties.

Result: Formulation composition with 2% soybean phosphatidylcholine and 10 mg THC exhibited ∼94% entrapment efficiency, minimum particle size 101.32 nm, low polydispersity index 0.225 and +0.355 zeta potential. In situ liposomal dispersion containing 15% Pluronic® F127 turned into gel at nasal temperature. Cell lines were unharmed for 48 h. İn situ liposomal gels showed 1.5x higher blood concentration than the control formula.

Conclusion: In situ gels of liposomal THC formulations offer advantages over traditional nasal solutions, demonstrating comparable bioavailability to parenteral medication while also preserving the health of nasal mucosa cells.