Structural properties and release of insulin-loaded reverse hexagonal (HII) liquid crystalline mesophase

Mishraki-Berkowitz, Tehila; Aserin, Abraham; Garti, Nissim

doi:10.1016/j.jcis.2016.09.074

Cited by 19 publications

(6 citation statements)

References 50 publications

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“…The effect of protein incorporation was more evident on the hexagonal phase of GMO, rather than on the cubic one, and particularly in the presence of OA. In insulin-loaded GMO/OA, the elasticity of the hexagonal phase increased, likely because of the formation of more stabilized hydrophilic interactions at the lipid–water interface within the cylindrical structures forming the lattice, as also reported in ref . In GMO/OA 25% at temperature >50 °C, the presence of insulin determines a decrease in G ″ values and a weaker dependency of G ′ on frequency, indicating a more elastic behavior.…”

Section: Resultssupporting

confidence: 78%

“… 29 On the other hand, different modified reverse hexagonal systems based on GMO and co-surfactants were used by Garti and co-workers to explore the effect of confinement on the stability, morphology, and unfolding behavior of the protein upon heating or pH changes. 30 − 33 …”

Section: Introductionmentioning

confidence: 99%

“…In previous studies, GMO cubic structures were used to protect insulin from aggregation induced by either agitation, temperature, or enzymatic degradation . On the other hand, different modified reverse hexagonal systems based on GMO and co-surfactants were used by Garti and co-workers to explore the effect of confinement on the stability, morphology, and unfolding behavior of the protein upon heating or pH changes. − …”

Section: Introductionmentioning

confidence: 99%

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Cubic and Hexagonal Mesophases for Protein Encapsulation: Structural Effects of Insulin Confinement

et al. 2021

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Monoolein-based cubic and hexagonal mesophases were investigated as matrices for insulin loading, at low pH, as a function of temperature and in the presence of increasing amounts of oleic acid, as a structural stabilizer for the hexagonal phase. Synchrotron small angle X-ray diffraction, rheological measurements, and attenuated total reflection-Fourier transform infrared spectroscopy were used to study the effects of insulin loading on the lipid mesophases and of the effect of protein confinement in the 2D- and 3D-lipid matrix water channels on its stability and unfolding behavior. We found that insulin encapsulation has only little effects both on the mesophase structures and on the viscoelastic properties of lipid systems, whereas protein confinement affects the response of the secondary structure of insulin to thermal changes in a different manner according to the specific mesophase: in the cubic structure, the unfolding toward an unordered structure is favored, while the prevalence of parallel β-sheets, and nuclei for fibril formation, is observed in hexagonal structures.

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Section: Resultssupporting

confidence: 78%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cubic and Hexagonal Mesophases for Protein Encapsulation: Structural Effects of Insulin Confinement

et al. 2021

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“…The ATR-FTIR spectra of empty LNLCs M3 ( Figure 8 A) present (CH 3 ) and (CH 2 ) bending vibrations at 1375 and 1470 cm −1 , and Vs(CH 2 ) and Vas(CH 2 ) stretching vibrations at 2860 and 2930 cm −1 (band C) characteristic of aliphatic chains [ 55 , 56 ] present in both polymer (P407) and lipid (GMO). The asymmetric stretching vibrations of the unsaturation (trans) C=C assigned at 962 and 1670 cm −1 are only due to GMO component of LNLCs ( Figure 8 B) [ 55 , 57 ]. In addition, the stretching vibration of the carbonyl group (C=O) from the ester bond at 1670 cm −1 can only be attributed to GMO component of LNLCs.…”

Section: Resultsmentioning

confidence: 99%

pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance

et al. 2023

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Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.

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“…Lyotropic LCs form self-assembly by well biocompatible amphiphilic lipids, such as monoolein (MO), glyceryl monooleate (GMO), and phytantriol (PYT). PYT is one of the most widely studied amphiphiles creating the LCs’ matrices because of its nontoxic, well mucoadhesive, and biocompatible (Mishraki-Berkowitz et al., 2017; Yang et al., 2018). As the gel has good rheological characteristics, these lipid-based LCs were often selected for developing the gel-like preparations, which make them suitable for topical applications.…”

Section: Introductionmentioning

confidence: 99%

Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment

Wang

Zhang

et al. 2019

Drug Delivery

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The objective of this work was to investigate phytantriol-based liquid crystal (LC) gels including cubic (Q 2) and hexagonal (H 2) phase for ocular delivery of pilocarpine nitrate (PN) to treat glaucoma. The gels were produced by a vortex method and confirmed by crossed polarized light microscopy, smallangle X-ray scattering, and rheological measurements. Moreover, the release behaviors and permeation results of PN from the gels were estimated using in vitro studies. Finally, the anti-glaucoma effect of LC gels was evaluated by in vivo animal experiments. The inner structure of the gels was Pn3mtype Q 2 and H 2 phase, and both of them showed pseudoplastic fluid properties based on characterization techniques. In vitro release profiles suggested that PN could be sustainably released from LC gels within 48 h. Compared with eye drops, Q 2 and H 2 gel produces a 5.25-fold and 6.23-fold increase in the P app value (p < .05), respectively, leading to a significant enhancement of corneal penetration. Furthermore, a good biocompatibility and longer residence time on precorneal for LC gels confirmed by in vivo animal experiment. Pharmacokinetic studies showed that LC gels could maintain PN concentration in aqueous humor for at least 12 h after administration and remarkably improve the bioavailability of drug. Additionally, in vivo pharmacodynamics studies indicated that LC gels had a more significant intraocular pressure-lowering and miotic effect compared to eye drops. These research findings hinted that LC gels would be a promising pharmaceutical strategy for ocular application to enhance the efficacy of anti-glaucoma.

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Structural properties and release of insulin-loaded reverse hexagonal (HII) liquid crystalline mesophase

Cited by 19 publications

References 50 publications

Cubic and Hexagonal Mesophases for Protein Encapsulation: Structural Effects of Insulin Confinement

Cubic and Hexagonal Mesophases for Protein Encapsulation: Structural Effects of Insulin Confinement

pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance

Cubic and hexagonal liquid crystal gels for ocular delivery with enhanced effect of pilocarpine nitrate on anti-glaucoma treatment

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