研究目的
To investigate the potential of liquid crystalline gels for ophthalmic delivery to enhance the bioavailability of pilocarpine nitrate and overcome the limitations of traditional eye drops.
研究成果
The phytantriol-based lyotropic liquid crystalline gel demonstrated sustained release of pilocarpine nitrate, enhanced corneal permeability, good retention in the eye, and no irritation, making it a promising alternative to traditional eye drops for ophthalmic drug delivery, particularly for glaucoma treatment.
研究不足
The study is limited to in vitro, ex vivo, and animal models (rabbits), which may not fully translate to human applications. The gel's performance under varying physiological conditions and long-term stability were not extensively evaluated. Optimization of drug loading and scalability for industrial production are areas for future work.
1:Experimental Design and Method Selection:
The study involved preparing phytantriol-based lyotropic liquid crystalline gels using a vortex method with a fixed ratio of phytantriol to water (73:27 w/w). Various characterization techniques were employed, including crossed polarized light microscopy (CPLM), small-angle X-ray scattering (SAXS), attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy, and rheological studies. In vitro release was assessed using a dynamic dialysis method, ex vivo corneal penetration was evaluated using Franz-type cells, and in vivo studies included residence time and ocular irritation tests in rabbits.
2:Sample Selection and Data Sources:
Samples were prepared with different concentrations of pilocarpine nitrate (0%, 1%, 2%, 3% w/w). Freshly excised rabbit corneas were used for ex vivo studies, and New Zealand white rabbits were used for in vivo evaluations.
3:List of Experimental Equipment and Materials:
Equipment included a Shimadzu LC-16AT HPLC system, CPLM (CK-500), SAXS (Anton Paar SAXS mc2), ATR-FTIR spectrophotometer (Alpha P model), controlled stress rheometer (Discover DHR-2), and Franz-type diffusion cells. Materials included phytantriol, pilocarpine nitrate, oxidized L-glutathione, purified water, and other chemicals of analytical or HPLC grade.
4:Experimental Procedures and Operational Workflow:
Gels were prepared by heating phytantriol and aqueous PN solutions to 60°C, mixing, and vortexing. Characterization involved visual observation, CPLM, SAXS, ATR-FTIR, and rheology. In vitro release was conducted in simulated tear fluid, ex vivo permeation used rabbit corneas in Franz cells, and in vivo tests involved fluorescein sodium for residence time and a modified Draize test for irritation.
5:Data Analysis Methods:
Data were analyzed using Microsoft Excel 2010 and statistical tests (one-way ANOVA, Student's t-test). Release kinetics were fitted to zero-order, first-order, Higuchi, and Ritger-Peppas models. Permeability coefficients and corneal hydration levels were calculated using specific formulas.
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HPLC system
LC-16AT, SPD-16A
Shimadzu
Used for high-performance liquid chromatography analysis to determine the concentration of pilocarpine nitrate.
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Small-angle X-ray scattering
SAXS mc2
Anton Paar
Used for further structure analysis and phase identification of the liquid crystalline systems by measuring scattering patterns.
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ATR-FTIR spectrophotometer
Alpha P
Thermo Fisher Scientific
Used to record Fourier transform infrared spectra to evaluate molecular interactions within the liquid crystalline systems.
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Crossed polarized light microscopy
CK-500
Shanghai Caikon Optical Instrument Co., Ltd.
Used to qualitatively demonstrate the phase structure of the liquid crystalline gels by observing birefringence textures.
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Controlled stress rheometer
Discover DHR-2
Rheological Instruments TA
Used to investigate the rheological characteristics and viscoelasticity of the liquid crystalline gels.
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Franz-type diffusion cell
Used for ex vivo corneal penetration studies to measure the permeation of pilocarpine nitrate through rabbit corneas.
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Dialysis bag
10–12 KDa molecular weight cut off
Aladdin
Used in the dynamic dialysis method for in vitro release studies to contain the gel samples and allow drug diffusion.
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