ABSTRACT
Three different kinds of sinomenine in situ liquid crystal were prepared for different prescriptions, to investigate the rheological properties before and after in situ treatment and evaluate its feasibility for embolization. Rheological experiments were carried out with cone plate fixtures. Both the steady-state rheological and non-steady-state rheological properties of in-situ gels and the swelling gels were studied and compared. Steady-state rheological study results showed that all the three liquid embolic agents were non-newtonian fluid before and after in situ treatment, which would become less ropy when they were pressed with shear stress; their viscosities differed by 2-5 orders of magnitude. It had a yield value of about 10 Pa before in situ treatment and about 4 500 Pa after in situ treatment. All the six systems had thixotropy while their dynamic viscosities were not influenced by the shear rate, all less than 0.3 Pa·s before in situ treatment more than 1 Pa·s after in situ treatment, differing by an order of magnitude. The results of temperature sweeping showed a slight decrease with a steady rate in viscosity within the range of 10-50 °C, differing by 3-4 orders of magnitude. The results of unsteady rheology showed that there was no obvious linear viscoelastic region in the three kinds of agents, indicating the properties of liquid. After in situ treatment, their linear viscoelastic range γ<1% (No.3 was 5%), and their elastic modulus G' was larger than the viscous modulus G", indicating the properties of solid. Frequency scanning results showed that for the systems at low frequencies, G">G', system viscosity in a dominant position; while at high frequencies, G'>G", system elasticity in a dominant position. The results of compound viscosity test also proved that the liquid embolic agent in situ can form a cubic liquid crystal (the structure of No. 3 was destroyed after in situ treatment). The DHR-2 rheometer was used to investigate the rheological properties of in situ gels with three different prescriptions. The method is simple and the result is reliable, which can provide more theoretical reference for the evaluation and practical application of the product.
ABSTRACT
OBJECTIVE: To prepare and characterize sinomenine liquid crystal gel, study the rheological properties and in vitro transdermal properties and compare with sinomenine ointment and sinomenine hydrophilic gel. METHODS: Sinomenine liquid crystal gel was prepared by using phytanetriol-water system and then characterized by polarized light microscope(PLM)and small angle X-ray diffraction(SAXS). Using DHR-2 rheometer, the rheological properties of sinomenine liquid crystal gel were investigated and compared with those of sinomenine ointment and sinomenine hydrophilic gel. Modified Franz diffusion cell was used for in vitro transdermal experiment and the in vitro transdermal properties were compared with sinomenine hydrogels and ointments. RESULTS: The appearance of sinomenine liquid crystal gel was colorless, clear and transparent, and showed dark field under PLM. SAXS showed cubic phase. The rheological parameters were good. The steady-state infiltration rates of sinomenine liquid crystal gel, ointment and hydrophilic gel were 153.93, 119.99, and 106.89 μg·cm-2·h-1, and their 48 h cumulative permeation amounts(%)were 93.76%, 91.55%, and 87.60%, respectively. CONCLUSION: PLM and SAXS can be used to characterize the liquid crystal gel.The prepared sinomenine liquid crystal gel has good appearance and suitable rheology, and its infiltration rate and 48 h cumulative permeation amount are superior to those of ointment and hydrophilic gel, which provides theoretical reference for sinomenine percutaneous administration.