A Novel Molecular Reservoir Based on Reverse Self-Assembled Liquid Crystals - A New Strategy for Prolonging the Duration in Action of Analgesics

The aim of this study was to develop liquid crystal (LC) precursors to obtain novel long-acting analgesics for injection based on depot systems and compare the difference between the cubic and hexagonal precursors in delivering Diclofenac sodium (DS). Diclofenac sodium liquid crystal precursor injections were prepared and characterized, followed by in vitro release, pharmacodynamic, and pharmacokinetic studies. The optimal formulations were prepared with a ratio of Phytantriol/ethanol/water as 76:19:5 for cubic LC precursors, and a ratio of Phytantriol/ethanol/water/Vitamine-E acetate as 72:18:5:5 for hexagonal, both loading various drug dosages (2.5%, 3.75% and 5%), respectively. Polarized light microscopy and small angle diffraction confirmed that the precursors were isotropic fluids and transformed into gels with Pn3m or HII framework in water. Rheological studies have shown that precursors belong to Newtonian fluids and gels to pseudoplastic fluids. The release showed that the DS in the commercial injection (DS-inj) was completely liberated within 6 h, whereas only 46.55% and 49.73% of the DS in 2.5% cubic precursors and 2.5% hexagonal precursors were freed, respectively. Pharmacodynamic studies have shown that cubic, hexagonal and DS-inj raised the pain threshold in mice by 169.4%, 157.3% and 113.79%, respectively. The mean retention times of DS in cubic and hexagonal were 3.16 and 2.67 times longer than DS-inj, respectively, according to pharmacokinetic results. In conclusion, cubic and hexagonal are both promising analgesic sustained release formulations. In addition, based only on the current comparison, cubic seems to have a better long-acting effect.