Novel Spiropyran Amphiphiles and Their Application as Light- Responsive Liquid Crystalline Components Kristian J. Tangso, † Wye-Khay Fong, † Tamim Darwish, ‡ Nigel Kirby, § Ben J. Boyd,* ,† and Tracey L. Hanley* ,‡ † Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia ‡ Australian Nuclear Science and Technology Organization, Locked Bag 2001, Kirrawee DC, NSW 2232, Australia § SAXS/WAXS Beamline, Australian Synchrotron, Clayton, Victoria, Australia *S Supporting Information ABSTRACT: Light-responsive materials formed by liquid crystalline lipids in water have potential application to drug delivery through inclusion of photochromic additives such as spiropyran. A series of novel analogues of spiropyran (SP) have been synthesized with an SP headgroup that possess a C 8 (SP-OC), C 12 (SP-L), and C 16 (SP-P) tail to probe the influence of the length of the hydrophobic tail on their physicochemical properties and effect on behavior in liquid crystal matrices with a view to application as stimulus- responsive elements on ultraviolet irradiation. In addition, compounds possessing an oleyl (SP-OL) and phytanyl (SP-PHYT) tail, to mimic those of the “parent” reverse bicontinuous cubic (V 2 ) phase forming lipids, glyceryl monooleate (GMO) and phytantriol, were also prepared. The photochromic compounds were characterized by their melting points and photophysical behavior in solution using techniques including hot stage microscopy (HSM), differential scanning calorimetry (DSC), and UV− visible spectroscopy. Their effect on the equilibrium nanostructure of bulk V 2 phases and phase-switching kinetics after exposure to UV light was assessed using small-angle X-ray scattering (SAXS). The melting point of the SP derivatives decreased linearly with increasing chain length, which suggests that interactions between the head groups governed their melting point, rather than the van der Waals interactions between the tails. Changing the R group did not influence the equilibrium rate constants for the isomerization of SP. Phase transition temperatures of liquid crystalline (LC) matrices were influenced significantly by incorporation of the SP derivatives and were greatest when the photochromic compound possessed an intermediate tail length substituent compared to the short alkyl or bulkier moieties. The level of disruption of lipid packing, and hence phase structure, were dependent on the duration of UV exposure. ■ INTRODUCTION Lipid-based liquid crystalline systems are attracting increasing interest as a means of controlled release drug delivery. When amphiphilic lipids are present in excess water, they can self- assemble into thermodynamically stable liquid crystalline phases (often termed “mesophases” or just “phases”). 1−6 The nonlamellar mesophases of most current interest in drug delivery systems are the reversed bicontinuous cubic (V 2 ) phase and the reversed hexagonal (H 2 ) phase. Their ability to solubilize hydrophilic, hydrophobic, and amphiphilic drugs make them excellent candidates for use as drug delivery matrices (Figure 1). The most commonly studied lipids for forming V 2 phases in excess water are glyceryl monooleate (GMO) a dietary lipid, and phytantriol, an ingredient commonly used in the cosmetic industry; the chemical structures are illustrated in Figure 1. Lipid packing within the mesophase structure is a key determinant of the overall nanostructure formed in water and can be influenced by lipid concentration, temperature, pressure, additives, and solvent composition. 7−14 The nanostructure, in turn, is what dictates the rate at which drug is released, 13,15,16 and transitions between phases are of interest for triggering release of incorporated active ingredients. There are several variables that may be used for triggering phase transitions in situ after administration, including temperature, 13 salt, dilution, and pH. 17,18 Fong et al. 13 demonstrated that temperature-stimulated systems can provide drug release on demand. However, in practice there is potential for accidental activation of drug release in cases where direct application of temperature is used to stimulate the phase change, presenting a major limitation. A possible alternative could be to utilize additives that can induce a phase change in response to a more selective external stimulus such as light. 19−21 Received: April 18, 2013 Revised: June 7, 2013 Published: August 3, 2013 Article pubs.acs.org/JPCB © 2013 American Chemical Society 10203 dx.doi.org/10.1021/jp403840m | J. Phys. Chem. B 2013, 117, 10203−10210