Lipid-based lyotropic liquid crystalline phase transitions as a novel assay platform using birefringence as the visual signal output

Liu, Qingtao; Xiao, Yunxin; Hawley, Adrian; Boyd, Ben J.

doi:10.1039/d0tb00355g

Cited by 3 publications

(2 citation statements)

References 24 publications

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“…The presence of lipase (100 U/mL) hydrolysed the ester group of MLO inducing a transition from Q →Hexagonal phase ( H ) 48 , with the latter not linked to a burst release phenomenon (Fig. 2 ).…”

Section: Resultsmentioning

confidence: 99%

Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

et al. 2023

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Ulcerative colitis is a chronic inflammatory bowel disease that strongly affects patient quality of life. Side effects of current therapies necessitate new treatment strategies that maximise the drug concentration at the site of inflammation, while minimizing systemic exposure. Capitalizing on the biocompatible and biodegradable structure of lipid mesophases, we present a temperature-triggered in situ forming lipid gel for topical treatment of colitis. We show that the gel is versatile and can host and release drugs of different polarities, including tofacitinib and tacrolimus, in a sustained manner. Further, we demonstrate its adherence to the colonic wall for at least 6 h, thus preventing leakage and improving drug bioavailability. Importantly, we find that loading known colitis treatment drugs into the temperature-triggered gel improves animal health in two mouse models of acute colitis. Overall, our temperature-triggered gel may prove beneficial in ameliorating colitis and decreasing adverse effects associated with systemic application of immunosuppressive treatments.

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Section: Resultsmentioning

confidence: 99%

Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

et al. 2023

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“…To prove the occurrence of the expected transition, a series of SAXS experiments were carried out after the gel was soaked in 1 mL of HEPES (or, alternatively, in a buffer solution containing lipase) and incubated at 38 °C for 8 h. As shown in Figure 1f , the L phase absorbed heat and water during the release experiments reaching a cubic ( pn3m ) phase with a lattice parameters (a= 8.7 nm) and a water channel (d w = 4 nm) comparable with those obtained for a Pn3m phase at its maximum hydration level (46) . The presence of lipase (1000 U/mL) hydrolysed the ester group of MLO inducing a transition from Q → Hexagonal phase ( H ) (47) , with the latter not linked to a burst release phenomenon ( Figure 2 ). Based on this initial characterisation, we chose an 84% MLO and 16% water formulation for subsequent in vitro and in vivo studies, which had suitable rheological properties to pass through a small diameter animal feeding needle (size 20G) to further expand into a sponge-like system once injected into the rectum.…”

Section: Resultsmentioning

confidence: 99%

Temperature-triggeredin situforming lipid mesophase gel for local treatment of ulcerative colitis

Carone

Spalinger

Gaultney

et al. 2022

Preprint

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Ulcerative colitis (UC) is a chronic inflammatory bowel disease affecting the colonic mucosa. There is no cure for UC and its chronic relapsing/remitting nature strongly affects patient quality of life. Current treatment options frequently have significant side effects and remission rates are limited raising a demand for new treatment strategies. Novel therapeutic approaches that could maximize the drug concentration at the site of inflammation with minimal systemic exposure, like topical applications, would address this unmet clinical need. To date, few drug delivery systems (DDSs) have been designed to topically convey small molecules to the rectum and left-sided colon. Here, we developed and tested a drug delivery platform for topical treatment of UC based on a temperature-triggered in situ forming adhesive lipid gel (TIF-Gel). Due to its soft-gel consistency, its high encapsulation efficacy and its drug-controlled release, TIF-Gel suggests a more patient-friendly and effective application with respect to the rectal formulations currently available. Capitalizing on the biocompatible and biodegradable self-assembled structure of lipid mesophases (LMPs), we loaded TIF-Gel with tofacitinib (TOFA; an hydrophilic inhibitor of the enzymes Janus kinase 1 and 3) or TAC ( an hydrophobic immunosuppressive drug), both indicated in the treatment of UC. We designed and fully characterized our biocompatible lipid formulation in vitro and tested it in vivo using two different murine models of intestinal inflammation, in chemically-induced and T cell transfer-mediated models of colitis. Both approaches (TIF-Gel-TOFA and TIF-Gel-TAC) led to reduce either colitis disease severity or intestinal inflammation compared to vehicles, therefore showing therapeutic efficacy. Overall, our findings show that TIF-Gel can deliver drugs locally to the colonic mucosa to mitigate intestinal inflammatory disease in a pre-clinical model. They also suggest that, in a clinical setting, TIF-Gel might provide a patient-friendly approach to improve colitis while allowing a reduction of the adverse effects associated with a systemic therapy.

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A multispectral-sensor-based colorimetric reader for biological assays

Pirbhai

Albrecht

Tirrell

2021

Review of Scientific Instruments

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Tests that depend on changes in color are commonly used in biosensing. Here, we report on a colorimetric reader for such applications. The device is simple to construct and operate, making it ideal for research laboratories with limited resources or skilled personnel. It consists of a commercial multispectral sensor interfaced with a Raspberry Pi and a touchscreen. Unlike camera-based readers, this instrument requires no calibration of wavelengths by the user or extensive image processing to obtain results. We demonstrate its potential for colorimetric biosensing by applying it to the birefringent enzyme-linked immunosorbent assay. It was able to prevent certain false positives that the assay is susceptible to and lowered its limit of detection for glucose by an order of magnitude.

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Lipid-based lyotropic liquid crystalline phase transitions as a novel assay platform using birefringence as the visual signal output

Abstract: Digestible amphiphilic lipids offer an opportunity to use birefringence of self-assembled lipid phases as a signal for a new class of electronics-free and colour-free visual biosensor.

Cited by 3 publications

References 24 publications

Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

Temperature-triggered in situ forming lipid mesophase gel for local treatment of ulcerative colitis

Temperature-triggeredin situforming lipid mesophase gel for local treatment of ulcerative colitis

A multispectral-sensor-based colorimetric reader for biological assays

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