Influence of the swollen lyotropic liquid-crystalline emulsions phase on the penetration rate of active ingredients into the skin Mateo Michel Torino 1 , NahirVadra 1 , DiegoLamas 2 , Sebastian Suarez 1 1 School of Science, University of Buenos Aires, Argentina, 2 Institute of Emerging Technologies (ITECA), UNSAM-CONICET, Argentina This work aims to develop a physicochemical understanding of how an emulsion-like liquid-crystal (LC) matrix influences the percutaneous delivery of active pharmaceutical ingredients (APIs) for the treatment of infectious diseases (e.g., tuberculosis). Oral therapies have difficulties, such as drug-induced hepatotoxicity and treatment discontinuation. In this context, transdermal systems for anti-tuberculosis drug delivery are being explored. 1 These systems are non-invasive and are administered by the patient himself, which improves treatment compliance, avoids the first-pass liver treatment, and can also provide drug release over long periods. 2 Moreover, it has been reported that emulsions stabilized by liquid crystal phases have unique rheologic properties. In addition, the structures formed by the different LC phases can act as a host to hydrophilic, hydrophobic, or amphiphilic molecules. It could be located in several areas of the supramolecular structure3, promoting the controlled release of active ingredients. 4 In this work, we have extensively explored a water- oil-surfactants diagram. The LC phases with and without APIs (e.g. isoniazid, rifampin) were identified and characterized by polarized light optical microscopy (PLOM) and small and wide-angle X-ray scattering (SAXS/ WAXS). Also, in vitro diffusion was studied using a Franz cell with a full-thickness membrane of porcine epidermal tissue extracted with a scalpel from ears, being a generally accepted model to simulate human skin permeability. At least lamellar, mesh, rectangular/ribbon, and hexagonal LC phases have been found and characterized,in addition to non-CL emulsions, showing that the system under study has wide versatility. On the other hand, it has been shown that the analyte incorporation does not change the LC properties of the emulsions. Moreover, we have studied how some LC phases undergo a phase transformation over time. Between 15 and 20 days, we have seen, e.g., that some rectangular phase becomes lamellar. Furthermore, LCs phases reach a molten system after heating, and therefore isotropic. After subsequent cooling, the starting liquid-crystalline phase was recovered completely. Also, in most cases, an improvement in liquid crystalline parameters was observed, evidenced by more intense diffraction peaks and more defined birefringence. This phenomenon is known as thermal bleaching and is characteristic of this LC system. In turn, different melting temperatures were observed depending on the type of CL phase present, which may also be related to the thermal stability of each system. Finally, the results show that the water content is directly involved in the diffusion of isoniazid, a proof of concept of a host transported by aqueous channels. It is because, in lamellar CL phases, a decrease of the water concentration in the emulsion generates a reduction of the interlayer distances (decreases the aqueous channel), which modifies the transport of actives. In summary, we have succeeded formulating and optimizing a system where feasible to control the concentration of actives ingredients diffused through the biological membrane as a function of the CL phase formulated. References 1. https://doi.org/10.2147/IJN.S236277 2. https://doi.org/10.1038/nbt.1504 3. https://doi.org/10.4018/978-1-5225-0751-2.ch009 4. https://doi.org/10.1007/s40005-014-0165-9
L21
© The Author(s), 2021
Made with FlippingBook Learn more on our blog