Development and In Vitro Evaluation of Lyotropic Liquid Crystals for the Controlled Release of Dexamethasone

Abstract

In this study, amphiphilic polymers were investigated as biomaterials that can control dexamethasone (DXM) release. Such materials present interfacial properties in the presence of water and an oily phase that can result in lyotropic liquid crystalline systems (LLCS). In addition, they can form colloidal nanostructures similar to those in living organisms, such as bilayers and hexagonal and cubic phases, which can be exploited to solubilize lipophilic drugs to sustain their release and enhance bioavailability. It was possible to obtain lamellar and hexagonal phases when combining polyoxyethylene (20) cetyl ether (CETETH-20) polymer with oleic acid (OA), N-methylpyrrolidone (P), isopropyl myristate (IM), and water. The phases were characterized by polarized light microscopy (PLM), small-angle X-ray scattering (SAXS), rheological, textural, and bioadhesion analyses followed by an in vitro release assay. All samples showed elastic behavior in the rheology studies and hexagonal samples containing P and IM showed the highest adhesiveness. The drug release profile of all LLCS presented an average lag time of 3 h and was best fitted to the Korsmeyer-Peppas and Weibull models, with controlled release governed by a combination of diffusion and erosion mechanisms. These systems are potential carriers for DXM and can be explored in several routes of administration, providing potential advantages over conventional pharmaceutical forms.

Keywords: amphiphilic polymers; controlled release; dexamethasone; drug release; kinetic model; lyotropic liquid crystals; nanostructured systems.

Figure 1

Scheme showing how the skin was adapted for the textural analyzer for the bioadhesion study.

Figure 2

Ternary phase diagrams of CETETH 20 combined with oleic acid (OA), N-methylpyrrolidone (P), and isopropyl myristate (IM) as oily phases. OA1, OA2, IM1, IM2, OAP1, OAP2, P1, and P2 were the points chosen for characterization. (TD) translucent dispersion, (SSTS) semi-solid transparent systems, (ITLS) isotropic transparent liquid system, and (PS) phase separation.

Figure 3

Photomicrographs obtained using polarized light microscopy (PLM) that shows the streaks of the hexagonal phases (IM1, IM2, P1, and P2) and Maltese crosses of the lamellar phases (OA1, OA2, OAP1, and OAP2). The sample compositions are described in Table 1; (a) OA1; (b) OA2; (c) OAP1; (d) OAP2; (e) IM1; (f) IM2; (g) P1; (h) P2.

Figure 4

Small-angle X-ray scattering (SAXS) patterns of the formulations. The arrows indicate the considered peaks for the mesophase classifications.

Figure 5

The frequency sweep profile of the storage (G′) and loss moduli (G′′) of samples at 25 °C. DXM loaded formulations. The sample compositions are described in Table 1.

Figure 6

Textural parameters obtained using the textural profile analysis (TPA) test. OA and OAP: lamellar phases, P and IM: hexagonal phases. The compositions are described in Table 1.

Figure 7

Results of the ex vivo skin bioadhesion test. Data were collected at 25 ± 0.5 °C. The values represent the mean ± the standard deviation (S.D.) of three replicates. OA and OAP: lamellar phases, P and IM: hexagonal phases. The composition is described in Table 1.

Figure 8

Release profile of DXM-loaded liquid crystal formulations (0.1% w/w) described in Table 1.