Insulin Delivery In article number 2210392, Christoph E. Hagemeyer, Francesca Cavalieri, and co-workers report how biodegradable and charge-switchable phytoglycogen nanoparticles with glucose-sensitive phenylboronic acid groups and amine moieties can be engineered to form nanocomplexes with insulin for its rapid and efficient glucose-responsive delivery. Subcutaneous injection of nanocomplexes in two distinct diabetic mouse models helps to maintain normal glucose levels for up to 13 h.

Insulin delivery

Phenylboronic acid

10.1002/adma.202370146

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Overcoming Therapeutic Challenges of Antibiotic Delivery with Cubosome Lipid Nanocarriers

ACS Applied Materials & Interfaces (2024)

Brendan Dyett Sampa Sarkar Haitao Yu Jamie Strachan Calum J. Drummond

Low discovery rates for new antibiotics, commercial disincentives to invest, and inappropriate use of existing drugs have created a perfect storm of antimicrobial resistance (AMR). This "silent pandemic" of AMR looms as an immense, global threat to human health. In tandem, many potential novel drug candidates are not progressed due to elevated hydrophobicity, which may result in poor intracellular internalization and undesirable serum protein binding. With a reducing arsenal of effective antibiotics, enabling technology platforms that improve the outcome of treatments, such as repurposing existing bioactive agents, is a prospective option. Nanocarrier (NC) mediated drug delivery is one avenue for amplifying the therapeutic outcome. Here, the performance of several antibiotic classes encapsulated within the lipid-based cubosomes is examined. The findings demonstrate that encapsulation affords significant improvements in drug concentration:inhibition outcomes and assists in other therapeutic challenges associated with internalization, enzyme degradation, and protein binding. We emphasize that a currently sidelined compound, novobiocin, became active and revealed a significant increase in inhibition against the pathogenic Gram-negative strain, Pseudomonas aeruginosa. Encapsulation affords co-delivery of multiple bioactives as a strategy for mitigating failure of monotherapies and tackling resistance. The rationale in optimized drug selection and nanocarrier choice is examined by transport modeling which agrees with experimental inhibition results. The results demonstrate that lipid nanocarrier encapsulation may alleviate a range of challenges faced by antibiotic therapies and increase the range of antibiotics available to treat bacterial infections.

Nanocarriers

Biopharmaceutical

Repurposing

10.1021/acsami.4c00921

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An indirect generation of 1D M^II-2,5-dihydroxybenzoquinone coordination polymers, their structural rearrangements and generation of materials with a high affinity for H₂, CO₂ and CH₄

Dalton Transactions (2016)

Brendan F. Abrahams A. David Dharma Brendan Dyett Timothy A. Hudson Helen E. Maynard‐Casely

A series of solid-state structural transformations are found to accompany desolvation of relatively simple coordination polymers to yield materials that exhibit unexpected gas sorbing properties. Reaction of 1,2,4,5-tetrahydroxybenzene with M(II) salts (M = Mg, or Zn) in an alcohol/water solution in the presence of air affords cis-M(II)(C6H2O4(-II))(H2O)2·2H2O·xROH, (M = Mg, or Zn), crankshaft-like chains in which the absolute configurations of the chiral metal centres follow the pattern Δ Δ Λ Λ Δ Δ Λ Λ, and are hydrogen bonded together to generate spacious channels. When crystals of the crankshaft chain are air dried the crystals undergo a single crystal-to-powder rearrangement to form linear trans-M(II)(C6H2O4(-II))(H2O)2 chains. Further dehydration yields microporous solids that reversibly sorb H2, CH4 and CO2 with high sorption enthalpies.

10.1039/c5dt04095g

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Cubosome lipid nanocarriers for delivery of ultra-short antimicrobial peptides

Journal of Colloid and Interface Science (2024)

Biserka Lakic Raymond C. Beh Sampa Sarkar S.K. Yap Priscila Cardoso

Although antimicrobial peptides (AMPs) are a promising class of new antibiotics, their inherent susceptibility to degradation requires nanocarrier-mediated delivery. While cubosome nanocarriers have been extensively studied for delivery of AMPs, we do not currently understand why cubosome encapsulation improves antimicrobial efficacy for some compounds but not others. This study therefore aims to investigate the link between the mechanism of action and permeation efficiency of the peptides, their encapsulation efficacy, and the antimicrobial activity of these systems. Encapsulation and delivery of Indolicidin, and its ultra-short derivative, Priscilicidin, were investigated using SAXS, cryo-TEM and circular dichroism. Molecular dynamics simulations were used to understand the loading of these peptides within cubosomes. The antimicrobial efficacy was assessed against gram-negative (E. coli) and gram-positive (MRSA) bacteria. A high ionic strength solution was required to facilitate high loading of the cationic AMPs, with bilayer encapsulation driven by tryptophan and Fmoc moieties. Cubosome encapsulation did not improve the antimicrobial efficacy of the AMPs consistent with their high permeation, as explained by a recent 'diffusion to capture model'. This suggests that cubosome encapsulation may not be an effective strategy for all antimicrobial compounds, paving the way for improved selection of nanocarriers for AMPs, and other antimicrobial compounds.

Nanocarriers

10.1016/j.jcis.2024.07.232

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Encapsulation and Controlled Release of the Therapeutic Neuropeptides Somatostatin and Oxytocin from the Lipidic Bicontinuous Cubic Phase

Australian Journal of Chemistry (2020)

Jamie Strachan Durga Dharmadana Brendan Dyett Céline Valéry Charlotte E. Conn

Therapeutic delivery of neuropeptides including oxytocin and somatostatin is associated with numerous difficulties including low stability, low oral bioavailability, and a short half-life in vivo. For delivery to the brain, these issues are exacerbated by difficulties in crossing the blood–brain barrier. Lipid-based nanomaterials may offer specific advantages for the delivery of therapeutic peptides including good biocompatibility, retention of peptide activity, and controlled release properties. Herein we have investigated the use of the lipid bicontinuous cubic phase as a depot formulation for the controlled release of the neuropeptides oxytocin and somatostatin. Retention of the cubic architecture was confirmed up to high peptide concentrations of at least 30 mg mL−1 for both peptides. Encapsulation had only minimal effect on the peptide secondary structure in both cases. Controlled release of the peptides from the cubic phase was diffusion controlled over the first 24 h. The time-dependent self-assembly of somatostatin into nanofibrils within the bicontinuous cubic phase led to a unique two-stage release mechanism, with diffusion-controlled release of the peptide monomer over the first 24 h followed by a much slower linear release of the peptide from the nanofibrils. Results suggest that the lipid bicontinuous cubic phase is a highly prospective nanomaterial for the encapsulation and controlled release of neuropeptide therapeutics.

Nanomaterials

10.1071/ch19573

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AcceleratedFormation of H2 Nanobubblesfrom a Surface Nanodroplet Reaction

Figshare (2020)

Brendan Dyett Xuehua Zhang

The compartmentalization of chemical reactions within droplets has advantages in low costs, reduced consumption of reagents, and increased throughput. Reactions in small droplets have also been shown to greatly accelerate the rate of many chemical reactions. The accelerated growth rate of nanobubbles from nanodroplet reactions is demonstrated in this work. The gaseous products from the reaction at the nanodroplet surface promoted nucleation of hydrogen nanobubbles within multiple organic liquid nanodroplets. The nanobubbles were confined within the droplets and selectively grew and collapsed at the droplet perimeter, as visualized by microscopy with high spatial and temporal resolutions. The growth rate of the bubbles was significantly accelerated within small droplets and scaled inversely with droplet radius. The acceleration was attributed to confinement from the droplet volume and effect from the surface area on the interfacial chemical reaction for gas production. The results of this study provide further understanding for applications in droplet enhanced production of nanobubbles and the on-demand liberation of hydrogen.

Reaction rate

10.1021/acsnano.0c03059.s001

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pH‐Dependent Lyotropic Liquid Crystalline Mesophase and Ionization Behavior of Phytantriol‐Based Ionizable Lipid Nanoparticles (Small 20/2024)

Small (2024)

Haitao Yu Brendan Dyett Nigel Kirby Xudong Cai Mohamad El Mohamad

Lyotropic

Lyotropic liquid crystal

10.1002/smll.202470152

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