Targeted nanoliposomes to improve enzyme replacement therapy of Fabry disease.

The central nervous system represents a major target tissue for therapeutic approach of numerous lysosomal storage disorders. Fabry disease arises from the lack or dysfunction of the lysosomal alpha-galactosidase A (GLA) enzyme, resulting in substrate accumulation and multisystemic clinical manifestations. Current enzyme replacement therapies (ERTs) face limited effectiveness due to poor enzyme biodistribution in target tissues and inability to reach the brain.

Advancing coenzyme Q10 delivery with plant protein-based nanoparticle-mediated nanosuspensions.

Coenzyme Q10 (CoQ10) possesses significant health-promoting potential, yet its oral delivery encounters obstacles stemming from its distinctive physicochemical characteristics, such as poor solubility, sensitivity to environmental factors and low bioaccessibility. To overcome these challenges, we developed high-payload CoQ10 nanosuspensions (CQ@SPNP, CQ@RPNP, and CQ@WPNP) using plant-based protein nanoparticles (NPs) derived from soybean (SPNP), rice (RPNP), and walnut (WPNP). The nanosuspensions include spherical particles, characterized by small particle size (<230 nm), low polydispersity (PDI < 0.

Comparative analysis of granular starch hydrolysis and multi-structural changes by diverse α-amylases sources: Insights from waxy rice starch.

Three cultivars of waxy rice starch with different multi-scale structures were subjected to α-amylase hydrolysis to determine amylopectin fine structure, production of oligosaccharides, morphology, and crystallinity of the partially hydrolyzed starch granules. α-amylases hydrolyzed the amylopectin B2 chain during the initial stage of hydrolysis, suggesting that it is primarily located in the outer shell of the granules. For waxy rice starch with loose structure, α-amylases attacked the crystalline and amorphous regions simultaneously in the initial stage, while for starch granules with compact structure, the outer shell blocklet (crystalline structure) can be a hurdle for α-amylases to proceed to hydrolysis of the internal granule structure.

Stable nanovesicles formed by intrinsically planar bilayers.

Hypothesis: Quatsome nanovesicles, formed through the self-assembly of cholesterol (CHOL) and cetyltrimethylammonium bromide (CTAB) in water, have shown long-term stability in terms of size and morphology, while at the same time exhibiting high CHOL-CTAB intermolecular binding energies. We hypothesize that CHOL/CTAB quatsomes are indeed thermodynamically stable nanovesicles, and investigate the mechanism underlying their formation.

Experiments: A systematic study was performed to determine whether CHOL/CTAB quatsomes satisfy the experimental requisites of thermodynamically stable vesicles.

Engineering pH-Sensitive Stable Nanovesicles for Delivery of MicroRNA Therapeutics.

MicroRNAs (miRNAs) are small non-coding endogenous RNAs, which are attracting a growing interest as therapeutic molecules due to their central role in major diseases. However, the transformation of these biomolecules into drugs is limited due to their unstability in the bloodstream, caused by nucleases abundantly present in the blood, and poor capacity to enter cells. The conjugation of miRNAs to nanoparticles (NPs) could be an effective strategy for their clinical delivery.

Multifunctional silica-coated mixed polymeric micelles for integrin-targeted therapy of pediatric patient-derived glioblastoma.

Glioblastoma multiforme (GBM) remains a major cause of mortality because treatments are precluded by to the limited transport and penetration of chemotherapeutics across the blood-brain barrier. Pitavastatin (PTV) is a hydrophobic Food and Drug Administration (FDA)-approved anticholesterolemic agent with reported anti-GBM activity. In the present study, we encapsulate PTV in silica-coated polymeric micelles (SiO PMs) surface-modified with the cyclic peptide Arg-Gly-Asp-Phe-Val (cRGDfV) that actively targets the αβ integrin overexpressed in the BBB endothelium and GBM.

Order from Disorder with Intrinsically Disordered Peptide Amphiphiles.

Amphiphilic molecules and their self-assembled structures have long been the target of extensive research due to their potential applications in fields ranging from materials design to biomedical and cosmetic applications. Increasing demands for functional complexity have been met with challenges in biochemical engineering, driving researchers to innovate in the design of new amphiphiles. An emerging class of molecules, namely, peptide amphiphiles, combines key advantages and circumvents some of the disadvantages of conventional phospholipids and block copolymers.

Application of Quality by Design to the robust preparation of a liposomal GLA formulation by DELOS-susp method.

Fabry disease is a lysosomal storage disease arising from a deficiency of the enzyme α-galactosidase A (GLA). The enzyme deficiency results in an accumulation of glycolipids, which over time, leads to cardiovascular, cerebrovascular, and renal disease, ultimately leading to death in the fourth or fifth decade of life. Currently, lysosomal storage disorders are treated by enzyme replacement therapy (ERT) through the direct administration of the missing enzyme to the patients.

Lipid Nanoparticle RBD-hFc mRNA Vaccine Protects hACE2 Transgenic Mice against a Lethal SARS-CoV-2 Infection.

The COVID-19 pandemic led to development of mRNA vaccines, which became a leading anti-SARS-CoV-2 immunization platform. Preclinical studies are limited to infection-prone animals such as hamsters and monkeys in which protective efficacy of vaccines cannot be fully appreciated. We recently reported a SARS-CoV-2 human Fc-conjugated receptor-binding domain (RBD-hFc) mRNA vaccine delivered via lipid nanoparticles (LNPs).

Multidomain drug delivery systems of β-casein micelles for the local oral co-administration of antiretroviral combinations.

The antiretroviral (ARV) cocktailrevolved the treatment of the human immunodeficiency virus (HIV) infection. Drug combinations have been also tested to treat other infectious diseases, including the recentcoronavirus disease 2019 (COVID-19) outbreak. To simplify administration fixed-dose combinationshave been introduced, however, oral anti-HIV therapy still struggles with low oral bioavailability of many ARVs.

Impact of Chemical Composition on the Nanostructure and Biological Activity of α-Galactosidase-Loaded Nanovesicles for Fabry Disease Treatment.

Fabry disease is a rare lysosomal storage disorder characterized by a deficiency of α-galactosidase A (GLA), a lysosomal hydrolase. The enzyme replacement therapy administering naked GLA shows several drawbacks including poor biodistribution, limited efficacy, and relatively high immunogenicity in Fabry patients. An attractive strategy to overcome these problems is the use of nanocarriers for encapsulating the enzyme.

Directed Assembly of Multi-Walled Nanotubes and Nanoribbons of Amino Acid Amphiphiles Using a Layer-by-Layer Approach.

Monodisperse unilamellar nanotubes (NTs) and nanoribbons (NRs) were transformed to multilamellar NRs and NTs in a well-defined fashion. This was done by using a step-wise approach in which self-assembled cationic amino acid amphiphile (AAA) formed the initial NTs or NRs, and added polyanion produced an intermediate coating. Successive addition of cationic AAA formed a covering AAA layer, and by repeating this layer-by-layer (LBL) procedure, multi-walled nanotubes (mwNTs) and nanoribbons were formed.

Aminated Polysaccharide-Based Nanoassemblies as Stable Biocompatible Vehicles Enabling Crossing of Biological Barriers: An Effective Transdermal Delivery of Diclofenac Medicine.

A series of stable polysaccharide derivatives that spontaneously self-assemble into nanocarriers was synthesized by applying a reductive amination on chitosan. The prepared nanocarriers were comprehensively studied and found to allow encapsulation of molecular cargo in both aqueous and lipidic media and deliver this cargo across biological barriers. The nanocarriers have demonstrated effective transdermal delivery of diclofenac (Voltaren), a nonsteroidal anti-inflammatory drug, by increasing its skin permeation up to 100 vs the tested control.

A Combinatorial Library of Lipid Nanoparticles for RNA Delivery to Leukocytes.

Lipid nanoparticles (LNPs) are the most advanced nonviral platforms for small interfering RNA (siRNA) delivery that are clinically approved. These LNPs, based on ionizable lipids, are found in the liver and are now gaining much attention in the field of RNA therapeutics. The previous generation of ionizable lipids varies in linker moieties, which greatly influences in vivo gene silencing efficiency.

Delayed nucleation in lipid particles.

Metastable states in first-order phase-transitions have been traditionally described by classical nucleation theory (CNT). However, recently an increasing number of systems displaying such a transition have not been successfully modelled by CNT. The delayed crystallization of phospholipids upon super-cooling is an interesting case, since the extended timescales allow access into the dynamics.

Enhanced Thermostability and Anticancer Activity in Breast Cancer Cells of Laccase Immobilized on Pluronic-Stabilized Nanoparticles.

Laccases are multi-copper oxidase enzymes having widespread applications in various biotechnological fields. However, low stability of free enzymes restricts their industrial use. Development of effective methods to preserve and even increase the enzymatic activity is critical to maximize their use, though this remains a challenge.

Publisher Correction: Shape and fluctuations of frustrated self-assembled nano ribbons.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Shape and fluctuations of frustrated self-assembled nano ribbons.

Self-assembly is an important process by which nontrivial structures are formed on the sub-micron scales. Such processes are governed by chemical and physical principles that dictate how the molecular interactions affect the supramolecular geometry. Currently there is no general framework that links between molecular properties and the supramolecular morphology with its size parameters.

Discerning the Structure Factor of Charged Micelles in Water and Supercooled Solvent by Contrast Variation X-ray Scattering.

Sodium dodecyl sulfate (SDS) is a well-known anionic surfactant that forms micelles in various solvents including supercooled sugar-urea melt. Here, we explore the application of contrast variation small-angle X-ray scattering (SAXS) in discerning the structure and interactions of SDS micelles in aqueous solution and in a room-temperature supercooled solvent. The SAXS patterns can be analyzed in terms of a core-shell ellipsoid model.

Controlled micelle conjugation via charged peptide amphiphiles.

We report the first demonstration of nonionic detergent micelle conjugation and phase separation using purpose-synthesized, peptide amphiphiles, C -(Asp) and C -(Lys) . Clustering is achieved in two different ways. Micelles containing the negatively charged peptide amphiphile C -(Asp) are conjugated (a) via a water-soluble, penta-Lys mediator or (b) to micelles containing the C -(Lys) peptide amphiphile.

Formulating stable hexosome dispersions with a technical grade diglycerol-based surfactant.

We report on the phase behavior of a technical grade and commercially available diglycerol monoisostearate, C41V, and its use for the preparation of nanostructured liquid crystal dispersions (hexosomes). C41V in water forms a reverse hexagonal liquid crystal at room temperature and in a wide range of concentrations (0.5-95 wt%); this hexagonal liquid crystal is stable up to 70 °C.

Nanostructures, Faceting, and Splitting in Nanoliter to Yoctoliter Liquid Droplets.

Contrary to everyday experience, where all liquid droplets assume rounded, near-spherical shapes, the temperature-tuning of liquid droplets to faceted polyhedral shapes and to spontaneous splitting has been recently demonstrated in oil-in-water emulsions. However, the elucidation of the mechanism driving these surprising effects, as well as their many potential applications, ranging from faceted nanoparticle synthesis through new industrial emulsification routes to controlled-release drug delivery within the human body, have been severely hampered by the micron-scale resolution of the light microscopy employed to date in all in situ studies. Thus, the thickness of the interfacially frozen crystalline monolayer, suggested to drive these effects, could not be directly measured, and the low limit on the droplet size still showing these effects remained unknown.

A general platform for antibody purification utilizing engineered-micelles.

We introduce a new concept and potentially general platform for antibody (Ab) purification that does not rely on chromatography or specific ligands (e.g., Protein A); rather, it makes use of detergent aggregates capable of efficiently capturing Ab while rejecting hydrophilic impurities.