Alkylation of Spiropyran Moiety Provides Reversible Photo-Control over Nanostructured Soft Materials
© The Author(s) 2012
Received: 4 October 2011
Accepted: 16 November 2011
Published: 9 February 2012
The purpose of this study was to create a light responsive nanostructured liquid crystalline matrix using a novel alkylated spiropyran photochromic molecule (spiropyran laurate, SPL) as a light activated drug delivery system. The liquid crystal matrix, prepared from phytantriol, responds reversibly to changes in photoisomerism of SPL on irradiation, switching between the bicontinuous cubic and the reversed hexagonal liquid crystal structures, a change previously shown to dramatically alter drug release rate. In contrast, the non-derivatized spiropyran and spirooxazine photochromic compounds do not sufficiently disrupt the matrix on isomerization to induce the phase change. Thus, novel alkylated spiropyran has the potential to be an effective agent for use in liquid crystalline systems for reversible ‘on-demand’ drug delivery applications.
Light responsive soft materials have been proposed for many bioapplications, including the development of ‘on-demand’ drug delivery systems . Towards this goal, photochromic additives and photothermal nanoparticles have been used to impart photosensitivity into materials such as polymers and self assembly structures [2–5]. When exposed to specific wavelengths of UV light, photochromics can reversibly switch between two isomeric forms of the chemical species. This feature has lead to photochromic moieties, such as spiropyran and azobenzene, being incorporated into self assembled systems as a trigger for drug release [6–8].
Of particular interest is the photo-isomerization of spiropyrans, between the colorless, non-ionic spiro and the colored, charged merocyanine forms . This family of photochromics has been well studied and been shown to induce changes in materials such as liquid crystal phase structure , light-induced reversible dissolution of SP-modified block copolypeptide micelles for drug release  and modifying the self-assembly of lipid and surfactant membranes [11–14]. Notably, lipid-based liquid crystal materials are receiving current interest as pulsatile active release systems as they can form thermodynamically stable nanostructures, which control the rate of drug release from the material [15–20]. They can also be rendered pH responsive by inclusion of ionizable lipids for selective release during oral drug delivery . Sufficient disturbance in the lipid packing can cause a change in nanostructure and thus ‘trigger’ a change in drug release. Using small angle X-ray scattering (SAXS), we have previously shown reversible control over the nanostructure using temperature as a stimulus, and consequent drug release rates from the liquid crystal matrix both in vitro and in vivo . However, for some applications, direct heat is not practical and a non-invasive stimulus is necessary.
2 UV Characterization of Spiropyran Laurate
3 Effect of Photochromics on Nanostructure
Three structurally related photochromics added to a phytantriol-water liquid crystal matrix were compared in this study for their effectiveness in disrupting lipid packing on irradiation. Briefly, the photochromics, SP, SPL and SOX were pre-dissolved in phytantriol, and phosphate buffered saline (pH 7.4) was added to the lipid phase in a ratio of 1:1 (w:w) to ensure excess water conditions [10, 26, 27]. The samples were heated transiently to 70°C to enable vortex mixing three times, and left to equilibrate for 1 week at 25°C before irradiation experiments.
In order to exert the greatest effect on lipid packing, the photochromic molecules should align themselves in the lipid bilayer near the hydrophilic headgroups of the amphiphiles. We propose that the laurate tail on the amphiphilic spiropyran “anchors” the photochromic into this position, and so enhances the disruptive effect of the change in SPL structure on the lipid packing. In contrast, the charged merocyanine form of the SP has the potential to partition out of the lipid bilayer into the aqueous domain on ionization, thereby losing its ability to disrupt the lipid packing and nanostructure. The reason for the lack of effect on photoisomerisation of SOX is less clear. This small, hydrophobic molecule may preferentially reside in the hydrophobic regions at the intersection on the tails of the phytantriol, and hence its isomerization does not cause a substantial disruption to lipid packing. Future experiments are planned to confirm these hypotheses.
In this study, the effect of irradiation of liquid crystal containing the photochromic dyes spiropyran, its monolaurate derivative and structurally similar spirooxazine were compared. On irradiation with UV light, the liquid crystal matrix containing the spiropyran laurate (SPL) induced changes in the nanostructure, whereas the non-alkylated spiropyran and spirooxazine did not. Non-alkylated SP had little effect on structure, and is hypothesized to partition out of the nanostructure on ionization, resulting in little disruption to lipid packing. The UV response of the SPL–phytantriol matrix was also found to be reversible. It is anticipated that this approach can be applied to control changes in drug delivery rate from lyotropic liquid crystals, and hence provide novel, reversible, ‘on-demand’ drug delivery systems.
The application of these materials in drug delivery is anticipated to be via injection of an in situ ‘gelling’ lipid matrix. Administration of the matrix to e.g. subcutaneous tissue imbibes aqueous fluid forming the liquid crystalline structure in vivo. We have previously provided proof of concept for such a system responsive to temperature . Penetration of UV radiation into tissues is obviously a limitation for such a system, however recent work in the polymer field has shown how photochromic spiropyran systems can be activated by NIR irradiation of UV emitting upconverting nanoparticles , providing a potential route for practical application of the materials described in this study which we are currently investigating.
This research was undertaken on the SAXS/WAXS beamline at the Australian Synchrotron. We acknowledge the Australian Institute of Nuclear Science and Engineering (AINSE) for funding under AINGRA10057 and PGRA, and Stephen Mudie (Australian Synchrotron) and Tim Hughes (CSIRO) for their technical assistance.
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