Unveiling the power of liquid chromatography in examining a library of degradable poly(2-oxazoline)s in nanomedicine applications.

A library of degradable poly(2-alkyl-2-oxazoline) analogues (dPOx) with different length of the alkyl substituents was characterized in detail by gradient elution liquid chromatography. The hydrophobicity increased with increased side chain length as confirmed by a hydrophobicity row, established by reversed-phase liquid chromatography. Those dPOx were cytocompatible and formed colloidally stable nanoparticle (NP) formulations with positive zeta potential.

PEG-Lipid-PLGA Hybrid Particles for Targeted Delivery of Anti-Inflammatory Drugs.

Hybrid nanoparticles (HNPs) were designed by combining a PLGA core with a lipid shell that incorporated PEG-Lipid conjugates with various functionalities (-RGD, -cRGD, -NH, and -COOH) to create targeted drug delivery systems. Loaded with a neutral lipid orange dye, the HNPs were extensively characterized using various techniques and investigated for their uptake in human monocyte-derived macrophages (MDMs) using FC and CLSM. Moreover, the best-performing HNPs (i.

Knowledge-Based Design of Multifunctional Polymeric Nanoparticles.

Conventional drug delivery systems (DDS) today still face several drawbacks and obstacles. High total doses of active pharmaceutical ingredients (API) are often difficult or impossible to deliver due to poor solubility of the API or undesired clearance from the body caused by strong interactions with plasma proteins. In addition, high doses lead to a high overall body burden, in particular if they cannot be delivered specifically to the target site.

Ethoxy acetalated dextran nanoparticles for drug delivery: A comparative study of formulation methods.

Dextran-based polymers, such as ethoxy acetalated dextran (Ace-DEX), are increasingly becoming the focus of research as they offer great potential for the development of polymer-based nanoparticles as drug delivery vehicles. Their major advantages are the facile synthesis, straightforward particle preparation and the pH-dependent degradation of the particles that can be fine-tuned by the degree of acetalation of the polymer. In this study we have shown that Ace-DEX can not only compete against the commonly used and FDA-approved polymer poly(lactic--glycolic acid) (PLGA), but even has the potential to outperform it in its encapsulation properties, , for the herein used anti-inflammatory leukotriene biosynthesis inhibitor BRP-187.

Polymer-based particles against pathogenic fungi: A non-uptake delivery of compounds.

The therapy of life-threatening fungal infections is limited and needs urgent improvement. This is in part due to toxic side effects of clinically used antifungal compounds or their limited delivery to fungal structures. Until today, it is a matter of debate how drugs or drug-delivery systems can efficiently reach the intracellular lumen of fungal cells and how this can be improved.

Targeting of phagolysosomes containing conidia of the fungus Aspergillus fumigatus with polymeric particles.

Conidia of the airborne human-pathogenic fungus Aspergillus fumigatus are inhaled by humans. In the lung, they are phagocytosed by alveolar macrophages and intracellularly processed. In macrophages, however, conidia can interfere with the maturation of phagolysosomes to avoid their elimination.

Ethoxy acetalated dextran-based nanocarriers accomplish efficient inhibition of leukotriene formation by a novel FLAP antagonist in human leukocytes and blood.

Leukotrienes are pro-inflammatory lipid mediators generated by 5-lipoxygenase aided by the 5-lipoxygenase-activating protein (FLAP). BRP-201, a novel benzimidazole-based FLAP antagonist, inhibits leukotriene biosynthesis in isolated leukocytes. However, like other FLAP antagonists, BRP-201 fails to effectively suppress leukotriene formation in blood, which limits its therapeutic value.

Prediction of Nanoparticle Sizes for Arbitrary Methacrylates Using Artificial Neuronal Networks.

Particle sizes represent one of the key factors influencing the usability and specific targeting of nanoparticles in medical applications such as vectors for drug or gene therapy. A multi-layered graph convolutional network combined with a fully connected neuronal network is presented for the prediction of the size of nanoparticles based only on the polymer structure, the degree of polymerization, and the formulation parameters. The model is capable of predicting particle sizes obtained by nanoprecipitation of different poly(methacrylates).

Effect of Crystallinity on the Properties of Polycaprolactone Nanoparticles Containing the Dual FLAP/mPEGS-1 Inhibitor BRP-187.

Seven polycaprolactones (PCL) with constant hydrophobicity but a varying degree of crystallinity prepared from the constitutional isomers ε-caprolactone (εCL) and δ-caprolactone (δCL) were utilized to formulate nanoparticles (NPs). The aim was to investigate the effect of the crystallinity of the bulk polymers on the enzymatic degradation of the particles. Furthermore, their efficiency to encapsulate the hydrophobic anti-inflammatory drug BRP-187 and the final in vitro performance of the resulting NPs were evaluated.

Optimized Encapsulation of the FLAP/PGES-1 Inhibitor BRP-187 in PVA-Stabilized PLGA Nanoparticles Using Microfluidics.

The dual inhibitor of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E synthase-1 (mPGES-1), named BRP-187, represents a promising drug candidate due to its improved anti-inflammatory efficacy along with potentially reduced side effects in comparison to non-steroidal anti-inflammatory drugs (NSAIDs). However, BRP-187 is an acidic lipophilic drug and reveals only poor water solubility along with a strong tendency for plasma protein binding. Therefore, encapsulation in polymeric nanoparticles is a promising approach to enable its therapeutic use.

PLA/PLGA-Based Drug Delivery Systems Produced with Supercritical CO-A Green Future for Particle Formulation?

Supercritical carbon dioxide (SC-CO) can serve as solvent, anti-solvent and solute, among others, in the field of drug delivery applications, e.g., for the formulation of polymeric nanocarriers in combination with different drug molecules.

Formulation of Liver-Specific PLGA-DY-635 Nanoparticles Loaded with the Protein Kinase C Inhibitor Bisindolylmaleimide I.

Bisindolylmaleimide I (BIM-I) is a competitive pan protein kinase C inhibitor with anti-inflammatory and anti-metastatic properties, suggested to treat inflammatory diseases and various cancer entities. However, despite its therapeutic potential, BIM-I has two major drawbacks, i.e.

Encapsulation of the dual FLAP/mPEGS-1 inhibitor BRP-187 into acetalated dextran and PLGA nanoparticles improves its cellular bioactivity.

Background: Dual inhibitors of the 5-lipoxygenase-activating protein (FLAP) and the microsomal prostaglandin E synthase-1 (mPGES-1) may exert better anti-inflammatory efficacy and lower risks of adverse effects versus non-steroidal anti-inflammatory drugs. Despite these advantages, many dual FLAP/mPGES-1 inhibitors are acidic lipophilic molecules with low solubility and strong tendency for plasma protein binding that limit their bioavailability and bioactivity. Here, we present the encapsulation of the dual FLAP/mPGES-1 inhibitor BRP-187 into the biocompatible polymers acetalated dextran (Acdex) and poly(lactic-co-glycolic acid) (PLGA) via nanoprecipitation.

3rd generation poly(ethylene imine)s for gene delivery.

Cationic polymers play a crucial role within the field of gene delivery offering the possibility to circumvent (biological) barriers in an elegant way. However, polymers are accompanied either by a high cytotoxicity or low efficiency. In this study, a series of high molar mass poly(2-oxazoline)-based copolymers was synthesized introducing 2-ethyl-2-oxazoline, ethylene imine, and primary amine bearing monomer units representing a new generation of poly(ethylene imine) (PEI).

Local phytochemical response of Musa acuminata × balbisiana Colla cv. 'Bluggoe' (ABB) to colonization by Sternorrhyncha.

The interaction of two Sternorrhyncha species, the banana aphid (Pentalonia nigronervosa Coquerel (Hemiptera: Aphididae, Aphidinae)), vector of the banana bunchy top virus (BBTV), and the latania scale (Hemiberlesia lataniae Signoret (Hemiptera: Diaspididae, Diaspidinae)) with Musa acuminata × balbisiana Colla (ABB Group) 'Bluggoe' (Musaceae) was investigated by a combination of conventional and spatially resolved analytical techniques, H NMR, UHPLC-MS, and matrix-free UV-laser desorption/ionization MS imaging. After infestation, the feeding sites of P. nigronervosa on the pseudostem and the exocarp of banana fruit developed a red tinge, in which tissue-specific accumulations of phenylphenalenones were discovered.

PF2fit: Polar Fast Fourier Matched Alignment of Atomistic Structures with 3D Electron Microscopy Maps.

There continue to be increasing occurrences of both atomistic structure models in the PDB (possibly reconstructed from X-ray diffraction or NMR data), and 3D reconstructed cryo-electron microscopy (3D EM) maps (albeit at coarser resolution) of the same or homologous molecule or molecular assembly, deposited in the EMDB. To obtain the best possible structural model of the molecule at the best achievable resolution, and without any missing gaps, one typically aligns (match and fits) the atomistic structure model with the 3D EM map. We discuss a new algorithm and generalized framework, named PF(2) fit (Polar Fast Fourier Fitting) for the best possible structural alignment of atomistic structures with 3D EM.

Dextran-graft-linear poly(ethylene imine)s for gene delivery: importance of the linking strategy.

Low molar mass linear poly(ethylene imine)s (lPEI) were grafted onto dextran via different synthesis routes aiming at the elucidation of structure-property relationships of dextran-graft-linear poly(ethylene imine) (dex-g-lPEI) conjugates for gene delivery applications. Beside the molar mass of well-defined lPEIs and the linker unit, also the amount of lPEI in the polymeric vectors was varied. The synthesized dextran modifications were characterized regarding their chemical structure and showed enhanced complexation and stabilization of DNA against enzymatic degradation.

NONUNIFORM FOURIER TRANSFORMS FOR RIGID-BODY AND MULTI-DIMENSIONAL ROTATIONAL CORRELATIONS.

The task of evaluating correlations is central to computational structural biology. The rigid-body correlation problem seeks the rigid-body transformation (, ), ∈ SO(3), ∈ ℝ that maximizes the correlation between a pair of input scalar-valued functions representing molecular structures. Exhaustive solutions to the rigid-body correlation problem take advantage of the fast Fourier transform to achieve a speedup either with respect to the sought translation or rotation.

Parallel high-throughput screening of polymer vectors for nonviral gene delivery: evaluation of structure-property relationships of transfection.

In recent years, "high-throughput" (HT) has turned into a keyword in polymer research. In this study, we present a novel HT workflow for the investigation of cationic polymers for gene delivery applications. For this purpose, various poly(ethylene imine)s (PEI) were used as representative vectors and investigated via HT-assays in a 96-well plate format, starting from polyplex preparation up to the examination of the transfection process.

Fluorescence imaging of cancer tissue based on metal-free polymeric nanoparticles - a review.

The utilization of fluorescent nanoparticles (FNPs), which consist of organic fluorophores embedded into a polymer matrix, seems to be a promising concept for in vivo cancer imaging showing good biocompatibility, biodegradability, and low toxicity of the agents. Polymeric nanoparticles as fluorescent nanocarriers can be systematically designed with regard to the requested task, i.e.

Multi-gene-loci inheritance in resistance modeling.

The ability of an organism to degrade harmful substances to less toxic compounds is referred to as metabolic resistance. The biochemical processes result in a shift of dose-response curves associated with the toxic substances. Hence, the development of metabolic resistance may cause great problems of managing pests and diseases by pesticides.

Preparation, cellular internalization, and biocompatibility of highly fluorescent PMMA nanoparticles.

Methacrylate monomers were functionalized with a 4-hydroxythiazole chromophore and copolymerized with methyl methacrylate via RAFT. Nanoparticles of 120 and 500 nm in size were prepared without using stabilizers/surfactants. For comparative studies, preparative ultracentrifugation was applied for the separation into small and large particle fractions.

Uptake of well-defined, highly glycosylated, pentafluorostyrene-based polymers and nanoparticles by human hepatocellular carcinoma cells.

Chain length, size, composition, surface charge, and other properties of polymeric materials affect their recognition and uptake by cells and must be optimized to deliver polymers selectively to their target. However, it is often not possible to precisely modify selected properties without changing other parameters. To overcome these difficulties, well-defined poly(pentafluorostyrene)-based polymers are prepared that can be grafted via thiol/para-fluorine "click" reaction with 1-thio-β-D-glucose and 1-thio-β-D-galactose.

Labeled Nanoparticles Based on Pharmaceutical EUDRAGIT® S 100 Polymers.

The pharmaceutically important polymer P(MAA-r-MMA)(1:2) (EUDRAGIT(®) S100) was investigated concerning its behavior to form nanoparticles via nanoprecipitation. The particles obtained were characterized regarding their size, shape, and characteristics using DLS, SEM, and AUC. Furthermore, the P(MAA-r-MMA)(1:2) copolymer was modified with different markers in order to achieve polymer-based nanocarrier systems, which are detectable and may be useful for controlled drug delivery devices to monitor the drug pathways.