Systematic Investigation of Metabolic Oligosaccharide Engineering Efficiency in Intestinal Cells Using a Dibenzocyclooctyne-Monosaccharide Conjugate.

Metabolic oligosaccharide engineering (MOE) of cells with synthetic monosaccharides can introduce functionality to the glycans of cell membranes. Unnatural sugars (e. g., peracetylated mannose-azide) can be expressed on the cell surface with the azide group in place. After MOE, the azide group can participate in a copper-free click reaction with an alkyne (e. g., dibenzocyclooctyne, DBCO) probe. This allows the metabolic fate of monosaccharides in cells to be understood. However, in a drug delivery context it is desirable to have azide groups on the probe (e. g. a drug delivery particle) and the alkyne (e. g. DBCO) on the cell surface. Consequently, the labelling efficiency of intestinal cell lines (Caco-2 and HT29-MTX-E12) treated with N-dibenzocyclooctyne-tetra-acetylmannosamine, and the concentration- and time-dependent labelling were determined. Furthermore, the labelling of mucus in HT29-MTX-E12 cells with DBCO was shown. This study highlights the potential for using MOE to target azide-functionalised probes to intestinal tissues for drug delivery applications.

Learning critical thinking skills online: can precision teaching help?

Critical thinking is identified as a key educational outcome in higher education curricula; however, it is not trivial to support students in building this multifaceted skill. In this study, we evaluated a brief online learning intervention focusing on informal fallacy identification, a hallmark critical-thinking skill. The intervention used a bite-sized video learning approach, which has been shown to promote student engagement. Video-based learning was implemented within a precision teaching (PT) framework, which modulates the exposure of individual learners to the learning material to enable them to build 'fluency' in the targeted skills. In one of the learning conditions, PT was applied synergistically with domain-general problem-based training to support generalisation. The intervention consisted of two learning episodes and was administered to three groups (learning conditions) of 19 participants each: a PT fluency-based training group; a PT + group, where PT was combined with problem-based training; and a self-directed learning control group. All three groups showed comparable improvements in fallacy identification on taught (post-episode tests) and unseen materials (post-intervention assessment), with lower-scoring participants showing higher gains than high-scoring participants. The results of the knowledge retention tests a week later were also comparable between groups. Importantly, in the domain-general fallacy-identification assessment (post-intervention), the two PT groups showed higher improvements than the control group. These findings suggest that the integration of bite-sized video learning technologies with PT can improve students' critical-thinking skills. Furthermore, PT, on its own or combined with problem-based training, can improve their skill to generalise learning to novel contexts. We discuss the educational implications of our findings.

Pluronic-Functionalized Silica-Lipid Hybrid Microparticles: Improving the Oral Delivery of Poorly Water-Soluble Weak Bases.

A Pluronic-functionalized silica-lipid hybrid (Plu-SLH) microparticle system for the oral delivery of poorly water-soluble, weak base drugs is reported for the first time. A highly effective Plu-SLH microparticle system was composed of Labrasol as the lipid phase, Pluronic F127 as the polymeric precipitation inhibitor (PPI), and silica nanoparticles as the solid carrier. For the model drug cinnarizine (CIN), the Plu-SLH delivery system was shown to offer significant biopharmaceutical advantages in comparison with unformulated drug and drug in the silica-lipid hybrid (SLH) system. In vitro two-phase dissolution studies illustrated significantly reduced pH provoked CIN precipitation and an 8- to 14-fold improvement in the extent of dissolution in intestinal conditions. In addition, under simulated intestinal digesting conditions, the Plu-SLH provided approximately three times more drug solubilization than the SLH. Oral administration in rats resulted in superior bioavailability for Plu-SLH microparticles, i.e., 1.6- and 2.1-fold greater than the SLH and the unformulated CIN, respectively. A physical mixture of Pluronic and SLH (Plu&SLH), having the same composition as Plu-SLH, was also evaluated, but showed no significant increase in CIN absorption when compared to unmodified CIN or SLH. This work represents the first study where different methods of incorporating PPI to formulate solid-state lipid-based formulations were compared for the impact on the biopharmaceutical performance. The data suggest that the novel physicochemical properties and structure of the fabricated Plu-SLH microparticle delivery system play an important role in facilitating the synergistic advantage of Labrasol and Pluronic F127 in preventing drug precipitation, and the Plu-SLH provides efficient oral delivery of poorly water-soluble weak bases.

The role of porous nanostructure in controlling lipase-mediated digestion of lipid loaded into silica particles.

The rate and extent of lipolysis, the breakdown of fat into molecules that can be absorbed into the bloodstream, depend on the interfacial composition and structure of lipid (fat) particles. A novel method for controlling the interfacial properties is to load the lipid into porous colloidal particles. We report on the role of pore nanostructure and surface coverage in controlling the digestion kinetics of medium-chain and long-chain triglycerides loaded into porous silica powders of different particle size, porosity, and hydrophobicity/hydrophilicity. An in vitro lipolysis model was used to measure digestion kinetics of lipid by pancreatic lipase, a digestive enzyme. The rate and extent of lipid digestion were significantly enhanced when a partial monolayer of lipid was loaded in porous hydrophilic silica particles compared to a submicrometer lipid-in-water emulsion or a coarse emulsion. The inhibitory effect of digestion products was clearly evident for digestion from a submicrometer emulsion and coarse emulsion. This effect was minimal, however, in the two silica-lipid systems. Lipase action was inhibited for lipid loaded in the hydrophobic silica and considered due to the orientation of lipase adsorption on the methylated silica surface. Thus, hydrophilic silica promotes enhanced digestion kinetics, whereas hydrophobic silica exerts an inhibitory effect on hydrolysis. Evaluation of digestion kinetics enabled the mechanism for enhanced rate of lipolysis in silica-lipid systems to be derived and detailed. These investigations provide valuable insights for the optimization of smart food microparticles and lipid-based drug delivery systems based on lipid excipients and porous nanoparticles.

Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

Magnetically-activated lipid nanocarriers in biomedical applications: A review of current status and perspective.

Magnetically-activated lipid nanocarriers have become a research hotspot in the field of biomedicine. Liposomes and other lipid-based carriers possess good biocompatibility as well as the ability to carrying therapeutic cargo with a range of physicochemical properties. Previous studies have demonstrated that magnetic materials have potential wide applications in clinical diagnosis and therapy, such as in MRI as contrast agents and in hyperthermic obliteration of cancer tissues. More recently magneto-thermal activation of lipid carriers to stimulate drug release has extended the range of further therapeutic benefits. Here, an overview of the current development of magnetically-activated lipid nanocarriers in the field of biomedicine is provided, including the methods of fabrication of the nanocarriers and their in vitro and in vivo performance. A discussion of the current barriers to translation of these materials as medicines is provided in the context of clinical and regulatory complexities of using magnetically responsive materials in therapeutic applications. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Implantable Materials and Surgical Technologies > Nanomaterials and Implants.

The road to achieving herd immunity: factors associated with Singapore residents' uptake and hesitancy of the COVID-19 vaccination.

OBJECTIVE: Achieving high vaccination rates is key to containing the coronavirus disease 2019 (COVID-19). This study evaluated the factors associated with uptake of the COVID-19 vaccine. METHODS: Six hundred and seventy-six respondents were surveyed online between May and June 2021. Data on demographics, perception of the COVID-19 pandemic, and vaccine willingness and hesitancy factors were collected. RESULTS: Approximately 54.6% of the respondents had received the COVID-19 vaccination. Age (p = 0.001), males (OR 1.7, 95% CI 1.1-2.6, p = 0.026), ethnicity (p = 0.004), occupation (p = 0.003)), working in healthcare (OR 6.1, 95% CI 2.8-13.2, p < 0.001), smoking (OR 3.3, 95% CI 1.3-8.8, p = 0.014), seeing vaccination as a social responsibility (OR 3.8, 95% CI 1.2-12.0, p = 0.022) and believing the vaccine is important to end the COVID-19 pandemic (OR 2.7, 95% CI 1.1-6.1, p = 0.020) were associated with greater vaccination uptake. CONCLUSION: Social responsibility and well-being of collective society are important values associated with vaccine uptake in an Asian society. Understanding factors behind vaccine uptake can help advise public health measures and strategies to achieve high levels of vaccination.

Silica-lipid hybrid (SLH) versus non-lipid formulations for optimising the dose-dependent oral absorption of celecoxib.

PURPOSE: To investigate the dose linearity of celecoxib (CEL) pharmacokinetics from various non-lipid and lipid-based formulations; to probe the mechanisms of CEL absorption from a nano-structured silica-lipid hybrid (SLH) microparticle dosage form. METHODS: Single-dose pharmacokinetic parameters of CEL were determined in fasted rats at dose levels of 5, 20 and 50 mg/kg in aqueous suspensions of pure CEL, Celebrex® and CEL-SLH microparticles formulated using medium-chain lipids (Miglyol 812 or Capmul MCM) and Aerosil® silica nanoparticles. An in vitro lipolysis model was used to characterise the dynamic solubilisation state of CEL under digesting conditions. RESULTS: CEL-SLH formulations and Celebrex® consistently produced a 2-fold higher maximum plasma concentration (C(max)) and bioavailability (AUC(0→∞)) than pure CEL in a dose-linear manner within the dose range of 5-50 mg/kg CEL (R² > 0.8). Lipolysis drug phase partition data indicate a 2.5-7.5-fold higher CEL solubilising capacity resulting from the digestion of SLH microparticles as compared to the simulated fasted state endogenous micelles. Strong correlations were obtained between maximum CEL solubilisation levels during lipolysis and in vivo pharmacokinetic parameters (R² > 0.9). CONCLUSIONS: Collectively, the results highlight the potential of the SLH microparticles in enhancing the bioavailability of CEL in a dose-linear manner as facilitated by supersaturated solubilisation of CEL in the intestinal milieu.

Magnetically-stimulated transformations in the nanostructure of PEGylated phytantriol-based nanoparticles for on-demand drug release.

Lipid-based liquid crystalline (LLC) systems are formed by the self-assembly of lipid materials in aqueous environments. The internal nanostructures of LLC systems can be manipulated using remote stimuli and have the potential to serve as 'on-demand' drug delivery systems. In this study, a magnetically-responsive system that displayed a transition in nanostructure from liposomes to cubosomes/hexasomes under external alternating magnetic field (AMF) was established by the incorporation of iron oxide nanoparticles (IONPs) into a PEGylated phytantriol (PHYT)-based LLC system. Small angle X-ray scattering (SAXS) was utilized to assess the equilibrium phase behaviour of the systems with different compositions of the lipids to find the optimized formulation. Time-resolved SAXS was then used to determine the dynamic transformation of nanostructures of the IONP-containing systems with the activation of AMF. The formulation containing PHYT and DSPE-PEG2000 at a 95 to 5 molar percent ratio produced a transition from lamellar phase to bicontinuous cubic phase, showing a slow-to-fast drug release profile. Inclusion of either 5 nm or 15 nm IONPs imparted magnetic-responsiveness to the system. The magnetically-responsive system produced an 'on-demand' drug delivery system from which the drug release was able to be triggered externally by AMF-stimulation.

Understanding selectivity of metabolic labelling and click-targeting in multicellular environments as a route to tissue selective drug delivery.

Cancer cells generally exhibit higher metabolic demands relative to that of normal tissue cells. This offers great possibilities to exploit metabolic glycoengineering in combination with bio-orthogonal chemistry reactions to achieve tumour site-targeted therapeutic delivery. This work addresses the selectivity of metabolic glycan labelling in diseased (i.e., cancer) versus normal cells grown in a multicellular environment. Dibenzocylooctyne (DBCO)-bearing acetylated-d-mannosamine (Ac4ManNDBCO) was synthesised to metabolically label three different types of cell lines originating from the human lung tissues: A549 adenocarcinomic alveolar basal epithelial cells, MeT5A non-cancerous mesothelial cells, and MRC5 non-cancerous fibroblasts. These cell lines displayed different labelling sensitivity, which trended with their doubling time in the following order: A549 ≈ MeT5A > MRC5. The higher metabolic labelling efficiency inherently led to a higher extent of specific binding and accumulation of the clickable N3-conjugated gold nanoparticles (N3-AuNps, core diameter = 30 nm) in the DBCO-glycan modified A549 and MeT5A cells, but to a less prominent effect in MRC5 cells. These findings demonstrate that relative rates of cell metabolism can be exploited using metabolic labelling to recruit nanotherapeutics whilst minimising non-specific targeting of surrounding tissues.

Silica nanoparticles to control the lipase-mediated digestion of lipid-based oral delivery systems.

We investigate the role of hydrophilic fumed silica in controlling the digestion kinetics of lipid emulsions, hence further exploring the mechanisms behind the improved oral absorption of poorly soluble drugs promoted by silica-lipid hybrid (SLH) microcapsules. An in vitro lipolysis model was used to quantify the lipase-mediated digestion kinetics of a series of lipid vehicles formulated with caprylic/capric triglycerides: lipid solution, submicrometer lipid emulsions (in the presence and absence of silica), and SLH microcapsules. The importance of emulsification on lipid digestibility is evidenced by the significantly higher initial digestion rate constants for SLH microcapsules and lipid emulsions (>15-fold) in comparison with that of the lipid solution. Silica particles exerted an inhibitory effect on the digestion of submicrometer lipid emulsions regardless of their initial location, i.e., aqueous or lipid phases. This inhibitory effect, however, was not observed for SLH microcapsules. This highlights the importance of the matrix structure and porosity of the hybrid microcapsule system in enhancing lipid digestibility as compared to submicrometer lipid emulsions stabilized by silica. For each studied formulation, the digestion kinetics is well correlated to the corresponding in vivo plasma concentrations of a model drug, celecoxib, via multiple-point correlations (R(2) > 0.97). This supports the use of the lipid digestion model for predicting the in vivo outcome of an orally dosed lipid formulation. SLH microcapsules offer the potential to enhance the oral absorption of poorly soluble drugs via increased lipid digestibility in conjunction with improved drug dissolution/dispersion.

Monocytic Cell-Induced Phase Transformation of Circulating Lipid-Based Liquid Crystalline Nanosystems.

Both lamellar and non-lamellar configurations are naturally present in bio-membranes, and the synthetic lipid-based liquid crystalline nano-assemblies, mimicking these unique structures, (including liposomes, cubosomes and hexosomes) are applicable in the controlled delivery of bioactives. However, it remains uncertain whether these nanosystems retain their original phase identity upon contact with blood circulating cells. This study highlights a novel biological cell flow-through approach at the synchrotron-based small angle X-ray scattering facility (bio-SAXS) to unravel their real-time phase evolution when incubated with human monocytic cells (THP-1) in suspension. Phytantriol-based cubosomes were identified to undergo monocytic cell-induced phase transformation from cubic to hexagonal phase periodicity. On the contrary, hexosomes exhibited time-dependent growth of a swollen hexagonal phase (i.e., larger lattice parameters) without displaying alternative phase characteristics. Similarly, liposomes remained undetectable for any newly evolved phase identity. Consequently, this novel in situ bio-SAXS study concept is valuable in delivering new important insights into the bio-fates of various lipid-based nanosystems under simulated human systemic conditions.

Coupling in vitro cell culture with synchrotron SAXS to understand the bio-interaction of lipid-based liquid crystalline nanoparticles with vascular endothelial cells.

Nonlamellar lipid-based liquid crystalline (LLC) nanoparticles possessing different internal nanostructures, specifically the 3D-ordered cubosomes (V2 phase) and the 2D-ordered hexosomes (H2 phase), are of increasing interest as drug delivery systems. To facilitate their development, it is important that we understand their interactions with healthy human umbilical vein endothelial cells (HUVECs). To this end, a 3D cells-in-a-tube model that recapitulates the basic morphology (i.e. tubular lumen) and in vivo microenvironment (i.e. physiological shear stress) of blood vessels was employed as a biomimetic testing platform, and the bio-nanoparticle interactions were compared with that of the conventional 2D planar cell culture. Confocal microscopy imaging revealed internalisation of the nanoparticles into HUVECs within 2 h and that the nanoparticle-cell interactions of cubosomes and hexosomes were not significantly different from one another. Low fluid shear stress conditions (i.e. venous simulation at 0.8 dynes/cm2) were shown to impose subtle effects on the degree of nanoparticle-cell interactions as compared with the static 2D culture. The unexpected similarity of cellular interactions between cubosomes and hexosomes was clarified via a real-time phase behaviour analysis using the synchrotron-based small-angle X-ray scattering (SAXS) technique. When the nanoparticles came into contact with HUVECs under circulating conditions, the cubosomes gradually evolved into hexosomes (within 16 min). In contrast, the hexosomes retained their original internal structure with minimal changes to the lattice parameters. This study highlights the need to couple cellular studies with high-resolution analytics such as time-resolved SAXS analysis to ensure that particle structures are verified in situ, enabling accurate interpretation of the dynamics of cellular interactions and potential bio-induced changes of particles intended for biomedical applications. Graphical abstract.

Magnetically-stimulated transformations in nanostructure of lipid mesophases: Effect of structure of iron oxide nanoparticles.

Nanostructured lipid-based liquid crystalline (LLC) systems can display different drug release rates and also be stimuli-responsive, rendering them the potential to serve as 'on-demand' drug delivery systems. In this study, a magnetically-responsive cubic phase nanocomposite was engineered by doping iron oxide nanoparticles (IONPs) into a phytantriol (PHYT)-based lipid that exhibits transformation in nanostructure under external alternating magnetic field (AMF). The effects of IONP surface hydrophilicity/hydrophobicity, size and concentration were determined in dispersed systems, and the effect of hydration state of the system was also assessed. Time-resolved small angle X-ray scattering (SAXS) was used to probe the impact of these variables on the transformation of nanostructure with and without the application of AMF. The inclusion of both hydrophobic and hydrophilic IONPs reduced the temperature of the phase transition from the inverted bicontinuous cubic (V2) phase to inverted hexagonal (H2) phase and imparted magnetic-responsiveness to the systems. The size of the IONPs played an important role in governing the phase reversibility of the dispersed systems, while the concentration of the IONPs had more impact on the phase behaviour of the bulk systems. These successfully demonstrated a completely reversible magneto-responsive phase transition in the nanostructured LLC systems through optimising the selection of IONPs.

Hexaarylbiimidazoles(HABI)-functionalized lyotropic liquid crystalline systems as visible light-responsive materials.

Hexaarylbiimidazoles (HABIs) are a promising class of photoswitchable molecule that have received little attention in the literature. Among them, (2,2'-dimethoxydiphenylimidazole)-1,1'-binaphthyl (HABI1) displays unusual negative photochromism and is responsive to green light. This study investigates the potential of HABIs to serve as photo-responsive actuators controlling the structure of lyotropic liquid crystalline (LLC) materials. HABI1 with four methyl chains and HABI2 with four dodecyl chains were synthesized. Time resolved small angle X-ray scattering was used to characterize the potential disruptive effects of HABIs on the nanostructure of LLC systems. HABIs underwent rapid isomerization under irradiation, with a very slow reversion in the dark in toluene and in the LLC matrix, demonstrating excellent stability and photo-fatigue resistant. HABIs completely triggered phase transitions in the phytantriol-based materials, and HABI2 generated a greater disruption than HABI1 on the lipid packing due to the enhanced steric influence. Tuning the lipid composition yielded systems that transitioned from a "slow release" lamellar phase to a "burst release" bicontinuous cubic phase upon light irradiation. Such systems therefore may exhibit a triggered release behavior upon a short time of irradiation, showing great potential in "on demand" drug delivery.

Self-Assembled Nanostructured Lipid Systems: Is There a Link between Structure and Cytotoxicity?

Self-assembly of lipid-based liquid crystalline (LLC) nanoparticles is a formulation art arising from the hydrophilic-lipophilic qualities and the geometric packing of amphiphilic lipid molecules in an aqueous environment. The diversity of commercialized amphiphilic lipids and an increased understanding of the physicochemical factors dictating their membrane curvature has enabled versatile architectural design and engineering of LLC nanoparticles. While these exotic nanostructured materials are hypothesized to form the next generation of smart therapeutics for a broad field of biomedical applications, biological knowledge particularly on the systemic biocompatibility or cytotoxicity of LLC materials remains unclear. Here, an overview on the interactions between LLCs of different internal nanostructures and biological components (including soluble plasma constituents, blood cells, and isolated tissue cell lines) is provided. Factors affecting cell-nanoparticle tolerability such as the type of lipids, type of steric stabilizers, nanoparticle surface charges, and internal nanostructures (or lipid phase behaviors) are elucidated. The mechanisms of cellular uptake and lipid transfer between neighboring membrane domains are also reviewed. A critical analysis of these studies sheds light on future strategies to transform LLC materials into a viable therapeutic entity ideal for internal applications.

Probing cell-nanoparticle (cubosome) interactions at the endothelial interface: do tissue dimension and flow matter?

In the research field of nanostructured systems for biomedical applications, increasing attention has been paid to using biomimetic, dynamic cellular models to adequately predict their bio-nano behaviours. This work specifically evaluates the biointeractions of nanostructured lipid-based particles (cubosomes) with human vascular cells from the aspects of tissue dimension (conventional 2D well plate versus 3D dynamic tubular vasculature) and shear flow effect (static, venous and arterial flow-mimicking conditions). A glass capillary-hosted, 3D tubular endothelial construct was coupled with circulating luminal fluid flow to simulate the human vascular systems. In the absence of fluid flow, the degree of cell-cubosome association was not significantly different between the 2D planar and the 3D tubular systems. Under flow conditions simulating venous (0.8 dynes per cm2) and arterial (10 dynes per cm2) shear stresses, the cell-cubosome association notably declined by 50% and 98%, respectively. This highlights the significance of shear-guided biointeractions of non-targeted nanoparticles in the circulation. Across all 2D and 3D cellular models with and without flow, cubosomes had little effect on the cell-cell contact based on the unchanged immunoexpression of the endothelial-specific intercellular junction marker PECAM-1. Interestingly, there were dissimilar nanoparticle distribution patterns between the 2D planar (showing discrete punctate staining) and the 3D tubular endothelium (with a more diffused, patchy fashion). Taken together, these findings highlight the importance of tissue dimension and shear flow in governing the magnitude and feature of cell-nanoparticle interactions.

Visible light-triggered cargo release from donor acceptor Stenhouse adduct (DASA)-doped lyotropic liquid crystalline nanoparticles.

Light-responsive nanocarriers are applicable as non-invasive, highly tunable and precisely controlled drug delivery systems. Here, we report a new nanocarrier system, achieved by doping D1, a type of green light-responsive donor acceptor Stenhouse adduct (DASA), into a lipid-based lyotropic liquid crystalline system. Time-resolved small angle X-ray scattering was used to confirm that the matrix underwent a rapid and fully reversible phase transition from lamellar to inverse cubic phase upon irradiation with green light (532 nm), reverting back on removal of light. Fluorescein isothiocyanate-dextran (FD4) was used as a model hydrophilic cargo. The release of cargo upon varying irradiation parameters was investigated in vitro which showed that irradiation can trigger a burst release of FD4 upon phase transition. This additive shows promise for the development of new visible light-activated, "on demand" drug delivery systems.

Naphthalocyanine as a New Photothermal Actuator for Lipid-Based Drug Delivery Systems.

One approach to address the substantial global burden of ocular diseases such as aged related macular degeneration is using light-activated drug delivery to obviate the need for highly invasive and frequent, costly intravitreal injections. To enable such systems, new light responsive materials are required. This communication reports the use of silicon 2,3-naphthalocyanine bis(trihexylsilyloxide) (SiNC), a small molecule photosensitizer, as a new actuator for triggering light responsive lipid-based drug delivery systems. Small-angle X-ray scattering was used to confirm that the addition of SiNC imparted light sensitivity to the lipid systems, resulting in a complete phase transition within 20 s of near-infrared irradiation. The phase transition was also reversible, suggesting the potential for on-demand drug delivery. When compared to the phase transitions induced using alternative light responsive actuators, gold nanorods and graphene, there were some differences in phase behavior. Namely, the phytantriol with SiNC system transitioned directly to the inverse micellar phase, skipping the intermediate inverse hexagonal structure. The photodynamic properties and efficiency in controlling the release of drug suggest that SiNC-actuated lipid systems have the potential to reduce the burden of repeated intravitreal injections.