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Antimicrobial resistance (AMR) poses a global health crisis demanding innovative solutions. Traditional antibiotics, though pivotal over the past century in combating bacterial infections, face diminished efficacy against evolving bacterial defense mechanisms, especially in Gram‐negative strains. This study explores self‐assembled ionizable lipid nanoparticles (LNPs) with the incorporation of two ionizable lipid components (one cationic, one anionic) in nanocarriers for advanced antimicrobial drug delivery of the broad‐spectrum antibiotic Piperacillin (Pip). Incorporating cationic ionizable lipid ALC‐0315, recognized as a functional lipid in the Pfizer‐BioNTech mRNA‐based SARS‐CoV‐2 vaccine, into LNPs allowed mesophase transition, pH responsiveness, and ionization behavior in acidic environments found in sites of bacterial infections, to be studied using synchrotron small angle X‐ray scattering, dynamic light scattering, and a 2‐(p‐toluidino)‐6‐naphthalene sulfonic acid assay. Incorporating another anionic ionizable lipid, oleic acid not only modulates the LNPs' physicochemical properties, such as size, internal phase nanostructure, and surface charge but also synergistically enhances the antimicrobial potency together with ALC‐0315 with a benefit enhancing permeability and fusion with bacterial membranes. This study introduces a strategy for tailoring ionizable lipid compositions in LNPs, providing a new approach to antimicrobial treatment contributing to the fight against AMR. [ABSTRACT FROM AUTHOR]

Cationic lipids are crucial in medical and biotechnological applications including cellular transfection and gene delivery. Ionizable cationic lipids are critical components of the mRNA‐based COVID vaccines while permanently charged cationic lipids have shown promise in cancer treatment. Despite significant research progress over the past few decades in designing improved, biocompatible cationic lipids, their transfection efficiency remains lower than that of viral vectors. Cationic lipids with additional functionalities like fusogenicity, stimuli‐responsiveness, targeting capabilities, and therapeutic activity have been engineered to improve their performance. This review highlights the importance of molecular hybridization toward the design of biocompatible cationic lipids having fusogenic, stimuli‐responsive, targeting, or therapeutic properties. This review mainly focuses on cationic lipids, having a permanent positive charge in the headgroup region, as these are typically employed to both increase cellular interactions and for improved loading, particularly for anionic nucleic acid‐based therapeutics and vaccines. Structure–activity relationships between the lipid chemical structure (headgroup, spacer, hydrocarbon chain) and, to a lesser extent, the self‐assembled nanostructure and the intrinsic biological activity of the multi‐functional cationic lipids are described. Finally, the challenges involved in developing smart lipids without affecting their inherent capacity to self‐assemble into structured nano‐carriers are discussed. [ABSTRACT FROM AUTHOR]

Gold(I)‐thiolate complexes have served as primary building blocks for diverse Au nanostructure synthesis strategies. A delicate approach to characterize and control Au(I)‐thiolate motif formation and assembly on the surface is needed as it can potentially solve challenges associated with utilizing gold nanomaterials in many applications. Here, the controllable generation of flower‐shaped surface gold nanostructures (FSGNs) is demonstrated by manipulating the formation‐assembly process of Au(I)‐dodecanethiolate motifs within nanoscale surface droplets. The morphology and structure of the resulting Au nanostructures are governed by internal convection flows and interfacial energy, modulated by the nanodroplet composition and substrate wettability. The obtained FSGNs are proven to act as versatile scaffolds for the selective generation of Au spiky nanostars. These FSGNs can also be utilized to functionalize nanodroplet‐based reactors, boosting the fluorescent intensity of Nile red (NR) fluorophores and decomposing NR via catalytic reaction. Remarkably, with FSGN functionalized droplets smaller than a radius of 500 nm, the decomposition rate of NR can reach ≈0.01 s−1. These results highlight a miniaturized, controllable, and automated method for the in situ production of 3D gold nanostructures on substrates, offering prospects for fast surface nanostructure fabrication and efficient environmental pollutant treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Oleogels represent one of the most important carriers for the delivery of lipophilic nutraceuticals. Phytosterols (PS), plant‐derived natural sterol compounds, are preferred for oleogel preparation due to their self‐assembly properties and health function. However, the relationship between the physical properties of PS‐based oleogels and the chemical stability of loaded bioactive compounds is still unclear. RESULTS: The influence of lecithin (LC) and glycerol monostearate (GMS) on the physical properties of PS‐based oleogels made of liquid coconut oil and the stability of curcumin as a model bioactive loaded in the oleogels was investigated. Results showed that the flow consistency index was much higher for GMS‐containing oleogels than that for LC‐containing oleogels. The optical microscopy and X‐ray scattering analysis showed that the addition of GMS in the PS oleogels promoted the formation of a crystal mixture with different crystal polymorph structures, whereas LC addition promoted the formation of needle‐like crystals of PS. Using curcumin as a model lipophilic nutraceutical, the GMS‐enriched PS oleogels with high crystallinity and flow consistency index exhibited a good retention ratio and scavenging activity of the loaded curcumin when stored at room temperature. CONCLUSION: This study shows that enhancing the firmness of oleogels made from PS and liquid coconut oil is beneficial to the retention and chemical stability of a loaded bioactive (curcumin). The findings of the study will boost the development of PS‐based oleogel formulations for lipophilic nutraceutical delivery. © 2022 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Serial crystallography of membrane proteins often employs high-viscosity injectors (HVIs) to deliver micrometre-sized crystals to the X-ray beam. Typically, the carrier medium is a lipidic cubic phase (LCP) media, which can also be used to nucleate and grow the crystals. However, despite the fact that the LCP is widely used with HVIs, the potential impact of the injection process on the LCP structure has not been reported and hence is not yet well understood. The self-assembled structure of the LCP can be affected by pressure, dehydration and temperature changes, all of which occur during continuous flow injection. These changes to the LCP structure may in turn impact the results of X-ray diffraction measurements from membrane protein crystals. To investigate the influence of HVIs on the structure of the LCP we conducted a study of the phase changes in monoolein/water and monoolein/buffer mixtures during continuous flow injection, at both atmospheric pressure and under vacuum. The reservoir pressure in the HVI was tracked to determine if there is any correlation with the phase behaviour of the LCP. The results indicated that, even though the reservoir pressure underwent (at times) significant variation, this did not appear to correlate with observed phase changes in the sample stream or correspond to shifts in the LCP lattice parameter. During vacuum injection, there was a three-way coexistence of the gyroid cubic phase, diamond cubic phase and lamellar phase. During injection at atmospheric pressure, the coexistence of a cubic phase and lamellar phase in the monoolein/water mixtures was also observed. The degree to which the lamellar phase is formed was found to be strongly dependent on the co-flowing gas conditions used to stabilize the LCP stream. A combination of laboratory-based optical polarization microscopy and simulation studies was used to investigate these observations. [ABSTRACT FROM AUTHOR]

Glaucoma, a major cause of irreversible blindness worldwide, is associated with elevated intraocular pressure (IOP) and progressive loss of retinal ganglion cells (RGCs) that undergo apoptosis. A mechanism for RGCs injury involves impairment of neurotrophic support and exogenous supply of neurotrophic factors has been shown to be beneficial. However, neurotrophic factors can have widespread effects on neuronal tissues, thus targeting neurotrophic support to injured neurons may be a better neuroprotective strategy. In this study, we have encapsulated LM22A-4, a small neurotrophic factor mimetic, into Annexin V-conjugated cubosomes (L4-ACs) for targeted delivery to injured RGCs in a model of acute IOP elevation, which is induced by acute IOP elevation. We have tested cubosomes formulations that encapsulate from 9% to 33% LM22A-4. Our data indicated that cubosomes encapsulating 9% and 17% LM22A-4 exhibited a mixture of Pn3m/Im3m cubic phase, whereas 23% and 33% showed a pure Im3m cubic phase. We found that 17% L4-ACs with Pn3m/Im3m symmetries showed better in-situ and in-vitro lipid membrane interactions than the 23% and 33% L4-ACs with Im3m symmetry. In vivo experiments showed that 17% L4-ACs targeted the posterior retina and the optic nerve head, which prevented RGCs loss and improved functional outcomes in a mouse model of acute IOP elevation. These results provide evidence that Annexin V-conjugated cubosomes-based LM22A-4 delivery may be a useful targeted approach to prevent the progression of RGCs loss in glaucoma. Recent studies suggest that the therapy of effectively delivering neurotrophic factors to the injured retinal ganglion cells (RGCs) could promote the survival of RGCs in glaucoma. Our present work has for the first time used cubosomes as an active targeted delivery system and have successfully delivered a neuroprotective drug to the damaged RGCs in vivo. Our new cubosomal formulation can protect apoptotic cell death in vitro and in vivo , showing that cubosomes are a promising drug carrier system for ocular drug delivery and glaucoma treatment. We have further found that by controlling cubosomes in Pn3m phase we can facilitate delivery of neuroprotective drug through apoptotic membranes. This data, we believe, has important implications for future design and formulation of cubosomes for therapeutic applications. [Display omitted] [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

The encapsulation of drugs in nanoparticles serves as an effective way to modify pharmacokinetics and therapeutic efficacy. Nanoparticles comprised of poly(d,l-lactide- co -glycolide) (PLGA) are well suited for this purpose; they are accessible using multiple synthesis methods, are highly biocompatible and biodegradable, and possess desirable drug release properties. In the present study, we have explored the effects of various formulation parameters on the physical properties of PLGA nanoparticles synthesised using a microfluidic assisted nanoprecipitation method and loaded with a model drug. PLGA nanoparticles, with diameters ranging from 165–364 nm, were produced using three alternate stabilisers; poly(vinyl alcohol) (PVA), d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), and didodecyldimethylammonium bromide (DMAB). Three additional formulations used PVA in addition to 20 wt-% 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP), 1,2-di- O -octadecenyl-3-trimethylammonium propane (DOTMA), and oleic acid. Spectrophotometric analysis demonstrated that the use of PVA increased the loading efficiency over that of TPGS and DMAB formulations, while the inclusion of oleic acid in the PVA formulation resulted in a further 3-fold increase in loading efficiency. In vitro release studies demonstrate that the inclusion of lipid additives significantly alters release kinetics; release was most rapid and complete in the formulation containing oleic acid, while the addition of DOTAP and DOTMA significantly reduced release rates. Finally, the antimicrobial activity of each formulation was tested against Staphylococcus aureus and Bacillus cereus , with minimum inhibitory concentrations nearing or exceeding that of free rifampicin. Rifampicin loaded PLGA nanoparticles were synthesised using a microfluidic assisted nanoprecipitation method. The effects of stabiliser and lipid additives on nanoparticle morphology, drug encapsulation efficiency, release kinetics, and antimicrobial activity are explored. [ABSTRACT FROM AUTHOR]