Papers by Khay Fong
On-demand drug delivery systems have the potential to optimise drug delivery by allowing drug adm... more On-demand drug delivery systems have the potential to optimise drug delivery by allowing drug administration as required. Lipid-based liquid crystalline matrices (LC) are increasingly explored as a means of controlled release drug delivery due to their biocompatibility and ability to incorporate and control the release drugs of a wide ranging size and polarity. The rate at which drug is released is ultimately determined by the mesophase nanostructure. This inbuilt ‘on-off’ switch for drug release affords the opportunity to manipulate drug delivery by influencing lipid packing by e.g. changing temperature. The utilisation of advanced synchrotron SAXS has allowed for the understanding of mechanisms by which transformations between lipid self-assembled structures take place. Understanding these interactions is essential in the development of self-assembled matrices for many bioapplications. Light-activated drug delivery systems have potential to provide a selective and non-invasive app...
International Journal of Pharmaceutics, 2011
Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery syst... more Lipid-based liquid crystalline materials are of increasing interest for use as drug delivery systems. The intricate nanostructure of the reversed bicontinuous cubic (V 2) and inverse hexagonal (H 2) liquid crystal matrices have been shown to provide diffusion controlled release of actives of varying size and polarity. In this study, we extend the understanding of release to other self-assembled phases, the micellar cubic phase (I 2) and inverse micelles (L 2). The systems are comparable as they were all prepared from the one lipid, glyceryl monooleate (GMO), which sequentially forms all four phases with increasing hexadecane (HD) content in excess water. Phase identity was confirmed by small angle X-ray scattering (SAXS). SAXS data indicated that four mesophases were formed with increasing HD content at 25 • C: V 2 phase (Pn3m space group) formed at 0-4% (w/w) HD, H 2 phase formed at 4-25% (w/w) HD, I 2 phase (Fd3m space group) formed at 25-40% (w/w) HD and finally L 2 phase formed at >40% (w/w) HD. Analogous compositions using phytantriol rather than GMO as the core lipid did not produce the I 2 phase, with only V 2 to H 2 to L 2 transitions being apparent with increasing HD concentration. In order to relate the liquid crystal phase structure to drug release rate, in vitro release tests were conducted by incorporating radio-labelled glucose as a model hydrophilic drug into the four GMO-based mesophases. It was found that the drug release followed first-order diffusion kinetics and was fastest from V 2 followed by L 2 , H 2 , and I 2. Drug release was shown to be significantly faster from bicontinuous cubic phase than the other mesophases, indicating that the state of the water compartments, whether open or closed, has a great influence on the rate of drug release. It is envisioned that liquid crystalline mesophases with slower release characteristics will more likely have potential applications as sustained release drug delivery systems, and hence that the bicontinuous cubic phase is not necessarily the best choice for a sustained release matrix.
The Journal of Physical Chemistry B, 2013
Light-responsive materials formed by liquid crystalline lipids in water have potential applicatio... more 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 stimulusresponsive 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.
Langmuir, 2014
High-symmetry lipid nanoparticles with internal bicontinuous cubic phase structure (cubosomes) ar... more High-symmetry lipid nanoparticles with internal bicontinuous cubic phase structure (cubosomes) are prepared from a simple emulsion containing a mixture of a nondigestible lipid (phytantriol) and a digestible short-chained triglyceride using enzymatic lipolysis of the incorporated short-chained triglyceride. The lipolytic products partition away from the nondigestible lipid, resulting in crystallization of the cubic-phase internal structure. Timeresolved small-angle X-ray scattering revealed the kinetics of the disorder-to-order transition, with cryo-transmission electron microscopy showing an absence of liposomes. The new approach offers a new "sideways" method for the generation of lipid-based nanostructured materials that avoids the problems of top-down and bottomup approaches.
Langmuir, 2012
Lipid-based liquid-crystalline matrixes provide a unique prospect for stimuli-responsive nanomate... more Lipid-based liquid-crystalline matrixes provide a unique prospect for stimuli-responsive nanomaterials, attributed to the ability to effect self-assembly of the lipids at the molecular level. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, with research progressing toward the use of in situ changes to nanostructure to control drug release. Toward this goal, we have previously communicated the ability to switch between nonlamellar structures using gold nanorod (GNR)−phytantriol-based liquid-crystalline hybrid nanomaterials as near-infrared light responsive systems (Fong et al. Langmuir 2010, 26, 6136− 6139). In this study, the effect of laser activation on matrix nanostructure with changes in a number of system variables including lipid composition, GNR aspect ratio, GNR concentration, and laser pulse time were investigated. The nanostructure of the matrix was followed using small-angle X-ray scattering, while both cryoFESEM and cryoTEM were used to visualize the effect of GNR incorporation into the liquid crystal nanostructure. The system response was found to be dependent on all variables, thus demonstrating the potential of these nanocomposite materials as reversible "on-demand" drug delivery applications.
Biointerphases, 2012
The purpose of this study was to create a light responsive nanostructured liquid crystalline matr... more 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.
Self-Assembled Supramolecular Architectures, 2012
ABSTRACT
Chem. Commun., 2015
A weak amphiphilic base, pyridinylmethyl linoleate, is blended with monolinolein, yielding mesoph... more A weak amphiphilic base, pyridinylmethyl linoleate, is blended with monolinolein, yielding mesophases with a pH-induced hexagonal-to-cubic transition at pH ≤ 5.5.
The purpose of this study was to create a light responsive nanostructured liquid crystalline matr... more 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.
Journal of Controlled Release, 2009
Lipid-based liquid crystalline materials have been proposed as controlled drug delivery systems. ... more Lipid-based liquid crystalline materials have been proposed as controlled drug delivery systems. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, however there has been little progress towards the use of in situ changes to nanostructure to control drug release. In this study, phytantriol and glyceryl monooleate-based bicontinuous cubic (Q 2 ) and inverse hexagonal (H 2 ) nanostructures have been designed to allow change to the nanostructure in response to external change in temperature, with a view to controlling drug release rates in vivo. Changes to nanostructure with temperature were confirmed by crossed polarised optical microscopy and small angle X-ray scattering. Phytantriol containing 3% (w/w) vitamin E acetate provided the necessary phase transition behaviour to progress this system to in vitro release and in vivo proof of concept studies. Using glucose as a model hydrophilic drug, drug diffusion was shown to be reversible on switching between the H 2 and Q 2 nanostructures at temperatures above and below physiological temperature respectively. An in vivo proof of concept study in rats showed that after subcutaneous administration of these materials, the changes in nanostructure induced by application of a heat or cool pack at the injection site stimulated changes in drug release from the matrix anticipated from in vitro release behaviour, thereby demonstrating the potential utility of these systems as 'on demand' drug release delivery vehicles.
Langmuir, 2010
The nanostructure of mesophase liquid crystals prepared from amphiphilic lipids controls the rate... more The nanostructure of mesophase liquid crystals prepared from amphiphilic lipids controls the rate of release of incorporated agents from the material, such as drug molecules, and reversible transition between different nanostructures essentially provides an "on-off" switch for release (Fong, W.-K.; Hanley, T.; Boyd, B. J. J. Controlled Release 2009, 135, 218-226). In this study, the incorporation of plasmonic hydrophobized gold nanorods (GNRs) permits reversible manipulation of nanostructure on-demand, by irradiation of the matrix using a near-infrared laser. Synchrotron small-angle X-ray scattering was used to probe the kinetics of the response of nanostructure to laser irradiation, and the specificity of the approach is shown by the lack of response in the absence of nanorods, or for GNR whose dimensions are not matched to the specific wavelength of the incident light.
Books by Khay Fong
This chapter contains sections titled: Lipid Self - Assembly and Transitions between Self - Assem... more This chapter contains sections titled: Lipid Self - Assembly and Transitions between Self - Assembled Structures Application of Self - Assembled Systems in Drug Delivery and the Case for Stimuli - Responsive Systems Stimuli - Responsive Systems Future Directions of Stimuli - Responsive Systems References Lipid Self - Assembly and Transitions between Self - Assembled StructuresApplication of Self - Assembled Systems in Drug Delivery and the Case for Stimuli - Responsive SystemsStimuli - Responsive SystemsFuture Directions of Stimuli - Responsive SystemsReferences
Thesis Chapters by Khay Fong
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Papers by Khay Fong
Books by Khay Fong
Thesis Chapters by Khay Fong