Phytantriol based liquid crystal provide sustained release of anticancer drug as a novel embolic agent

Abstract

Phytantriol has received increasing amount of attention in drug delivery system, however, the ability of the phytantriol based liquid crystal as a novel embolic agent to provide a sustained release delivery system is yet to be comprehensively demonstrated. The purpose of this study was to prepare a phytantriol-based cubic phase precursor solution loaded with anticancer drug hydroxycamptothecine (HCPT) and evaluate its embolization properties, in vitro drug release and cytotoxicity. Phase behavior of the phytantriol-solvent-water system was investigated by visual inspection and polarized light microscopy, and no phase transition was observed in the presence of HCPT within the studied dose range. Water uptake by the phytantriol matrices was determined gravimetrically, suggesting that the swelling complied with the second order kinetics. In vitro evaluation of embolic efficacy indicated that the isotropic solution displayed a satisfactory embolization effect. In vitro drug release results showed a sustained-release up to 30 days and the release behavior was affected by the initial composition and drug loading. Moreover, the in vitro cytotoxicity and anticancer activity were evaluated by MTT assay. No appreciable mortality was observed for NIH 3T3 cells after 48 h exposure to blank formulations, and the anticancer activity of HCPT-loaded formulations to HepG2 and SMMC7721 cells was strongly dependent on the drug loading and treatment time. Taken together, these results indicate that phytantriol-based cubic phase embolic gelling solution is a promising potential carrier for HCPT delivery to achieve a sustained drug release by vascular embolization, and this technology may be potential for clinical applications.

Nature‐Inspired Design and Application of Lipidic Lyotropic Liquid Crystals

“…In terms of broader use in medicine, the highly viscous rheological property of cubic mesophases has led to their investigation as an in situ embolic agent, with a view to deployment against hepatic cancer . The formation of a “plug” of cubic phase by transformation of a locally injected solvent‐containing precursor to a solvent‐free lipid‐water mesophase in the blood vessel provides a temporary blockage and provides slow release of drug.…”

Oral and transdermal drug delivery systems: role of lipid-based lyotropic liquid crystals

“…Swelling of the PT matrices obeyed second-order kinetics and thus showed potential for clinical applications. 66 LC systems were developed for the antibacterial agent poly(hexamethylene biguanide) hydrochloride with a GMO and water system, enabling delivery to buccal mucosa in a controlled drug release manner and improving its mucoadhesive properties. 67 A lipid-based LC system increased the bioavailability not only for active synthetic pharmaceuticals and macromolecules but also for baicalein, a natural product from the root of Scutellaria baicalensis Georgi.…”

Smart phase transformation system based on lyotropic liquid crystalline@hard capsules for sustained release of hydrophilic and hydrophobic drugs

“…The special structures provide incorporation of drugs with different solubility, including hydrophilic, hydrophobic and amphiphilic molecules (Conn & Drummond, 2013;Rajabalaya et al, 2017) and also tunable release rate (Rizwan & Boyd, 2015;Abd-Allah et al, 2016;Huang & Gui, 2018). LLC exhibits perfect performance on mucosal (Huang et al, 2017), transdermal (Peng et al, 2015;Musa et al, 2017), periodontal (Mei et al, 2017a;Zheng et al, 2018), subcutaneous (Mei et al, 2017b) and other parenteral drug delivery (Wan et al, 2015;Qin et al, 2016), due to its high drug-loading capacity, appropriate viscoelasticity and good biocompatibility (Abd-Allah et al, 2016;Kulkarni & Thareja, 2016).…”

“…Glyceryl monooleate (GMO) and phytantriol (PYT) were the most common materials for the fabrication of LLC (Leung & Leal, 2019;Jie et al, 2019). GMO was chosen as the model lipid material in present study, which possessed lower MP and desirable biodegradability comparing with PYT (Qin et al, 2016;Owens et al, 2016). GMO was proved as excipients for oral administration in many countries (Nardin & K€ ollner, 2019).…”