Polycaprolactone/α-cyclodextrin polyrotaxanes with cellular uptake enhancing properties.

Biodegradable poly(ε-caprolactone) (PCL) was rotaxanated with α-cyclodextrin (α-CD) and an α-CD/2-hydroxypropyl-α-CD (HP-α-CD) mixture. Stoppering was achieved using 2-mercaptosuccinic acid (MSA) disulfide linkage. The structures of these polymeric supramolecular entities were confirmed by H NMR, with 75-80 wt% threaded CD, while the molar mass of the polyrotaxanes was around 18 kDa, determined by gel permeation chromatography.

Charge-converting nanocarriers: Phosphorylated polysaccharide coatings for overcoming intestinal barriers.

For the design of charge-converting nanocarriers (NCs), cationic lipid-based NCs containing curcumin as model drug were coated with phosphorylated starch (NC-SP) and phosphorylated dextran (NC-DP). NCs showed a drug encapsulation efficiency of 94 % and had a mean size of 175 to 180 nm. The recorded zeta potential of the core NC (cNC) was +8.

Antibiotic-Polyphosphate Nanocomplexes: A Promising System for Effective Biofilm Eradication.

Purpose: The eradication of bacterial biofilms poses an enormous challenge owing to the inherently low antibiotic susceptibility of the resident microbiota. The complexation of antibiotics with polyphosphate can substantially improve antimicrobial performance.

Methods: Nanoparticular complexes of the model drug colistin and polyphosphate (CP-NPs) were developed and characterized in terms of their particle size and morphology, polydispersity index (PDI), zeta potential, and cytotoxicity.

Oral formulations for highly lipophilic drugs: Impact of surface decoration on the efficacy of self-emulsifying drug delivery systems.

Aim: To evaluate the impact of the surface decoration of cannabidiol (CBD) loaded self-emulsifying drug delivery systems (SEDDS) on the efficacy of the formulations to cross the various barriers faced by orally administered drugs.

Methods: Polyethylene glycol (PEG)-free polyglycerol (PG)-based SEDDS, mixed zwitterionic phosphatidyl choline (PC)/PEG-containing SEDDS and PEG-based SEDDS were compared regarding stability against lipid degrading enzymes, surface properties, permeation across porcine mucus, cellular uptake and cytocompatibility.

Results: SEDDS with a size of about 200 nm with narrow size distributions were developed and loaded with 20-21 % of CBD.

Biomedical applications of functional hydrogels: Innovative developments, relevant clinical trials and advanced products.

Functional hydrogels are used for numerous biomedical applications such as tissue engineering, wound dressings, lubricants, contact lenses and advanced drug delivery systems. Most of them are based on synthetic or natural polymers forming a three-dimensional network that contains aqueous media. Among synthetic polymers, poly(meth)acrylates, polyethyleneglycols, poly(vinylalcohols), poly(vinylpyrrolidones), PLGA and poly(urethanes) are of high relevance, whereas natural polymers are mainly polysaccharides such as hyaluronic acid, alginate or chitosan and proteins such as albumin, collagen or elastin.

The CryoEM structure of human serum albumin in complex with ligands.

Human serum albumin (HSA) is the most prevalent plasma protein in the human body, accounting for 60 % of the total plasma protein. HSA plays a major pharmacokinetic function, serving as a facilitator in the distribution of endobiotics and xenobiotics within the organism. In this paper we report the cryoEM structures of HSA in the apo form and in complex with two ligands (salicylic acid and teniposide) at a resolution of 3.

Unveiling the potential of biomaterials and their synergistic fusion in tissue engineering.

Inspired by nature, tissue engineering aims to employ intricate mechanisms for advanced clinical interventions, unlocking inherent biological potential and propelling medical breakthroughs. Therefore, medical, and pharmaceutical fields are growing interest in tissue and organ replacement, repair, and regeneration by this technology. Three primary mechanisms are currently used in tissue engineering: transplantation of cells (I), injection of growth factors (II) and cellular seeding in scaffolds (III).

Comparative Analysis of PEG-Free and PEG-Based Self-Emulsifying Drug Delivery Systems for Enhanced Oral Bioavailability of Therapeutic (Poly) Peptides.

This study aims to compare the potential of Polyethylene glycol (PEG-free and PEG-based self-emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P and dissociation behavior.

Histidine-based ionizable cationic surfactants: novel biodegradable agents for hydrophilic macromolecular drug delivery.

The aim of this study was to design surfactants based on histidine (His) for hydrophobic ion-pairing and evaluate their safety and efficacy. Lauryl, palmitoyl and oleyl alcohol, as well as 2-hexyl-1-decanol were converted into surfactants with histidine as head-group via esterification. The synthesized His-surfactants were characterized regarding pK, critical micellar concentration (CMC), biodegradability, toxicity on Caco-2 cells, and ability to provide endosomal escape.

Safety, tolerability, and efficacy of NLY01 in early untreated Parkinson's disease: a randomised, double-blind, placebo-controlled trial.

Background: Converging lines of evidence suggest that microglia are relevant to Parkinson's disease pathogenesis, justifying exploration of therapeutic agents thought to attenuate pathogenic microglial function. We sought to test the safety and efficacy of NLY01-a brain-penetrant, pegylated, longer-lasting version of exenatide (a glucagon-like peptide-1 receptor agonist) that is believed to be anti-inflammatory via reduction of microglia activation-in Parkinson's disease.

Methods: We report a 36-week, randomised, double-blind, placebo-controlled study of NLY01 in participants with early untreated Parkinson's disease conducted at 58 movement disorder clinics in the USA.

Power-Up for Mucoadhesiveness: Two Generations of Thiolated Surfactants for Enhanced Sticky Nanoemulsions.

Nanoemulsions can be tuned toward enhanced gastro-intestinal retention time by incorporating thiolated surfactants into their surface. Tailoring the chemical reactivity of the thiol headgroup has major influence on mucoadhesive features of the nanoemulsion. Two generations of thiolated surfactants were synthetically derived from PEG-40-stearate featuring either a free thiol group or an S-protected thiol group.

Self-Emulsifying Drug Delivery Systems (SEDDS) Containing Reverse Micelles: Advanced Oral Formulations for Therapeutic Peptides.

Alternative methods to hydrophobic ion pairing for the formation of lipophilic complexes of peptide drugs to incorporate them in lipid-based nanocarriers such as self-emulsifying drug delivery systems (SEDDS) for oral administration are highly on demand. Such an alternative might be reverse micelles. Within this study, SEDDS containing dry reverse micelles (dRMs ) formed with an anionic (sodium docusate; AOT), cationic (dimethyl-dioctadecyl-ammonium bromide; DODAB), amphoteric (soy lecithin; SL), or non-ionic (polysorbate 85; P85) surfactant loaded with the model peptide drug polymyxin B (PMB) are developed.

Iminated aminoglycosides in self-emulsifying drug delivery systems: Dual approach to break down the microbial defense.

Hypothesis: Aminoglycosides are well known, cationic antimicrobial drugs. However, biofilm-based antibiotic resistance significantly limits their efficacy. Masking the polycationic character of these drugs, followed by incorporation into self-emulsifying drug delivery systems (SEDDS) can improve biofilm eradication.

Digestion of lipid excipients and lipid-based nanocarriers by pancreatic lipase and pancreatin.

The digestion behaviour of lipid-based nanocarriers (LNC) has a great impact on their oral drug delivery properties. In this study, various excipients including surfactants, glycerides and waxes, as well as various drug-delivery systems, namely self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) were examined via the pH-stat lipolysis model. Lipolysis experiments with lipase and pancreatin revealed the highest release of fatty acids for medium chain glycerides, followed by long chain glycerides and surfactants.

Web-based COVID-19 risk communication by religious authorities in Uganda: a critical review.

The objectives of this study were to explore the content of web-based communication on COVID-19 by religious authorities (RAs) in Uganda and to assess the level of integration of the Uganda Ministry of Health (MoH) and World Health Organisation (WHO) COVID-19 risk communication guidelines into the statements released by these RAs. A grey literature review was conducted by searching the websites of intra- and inter-religious bodies for the terms "COVID-19" and "coronavirus". Thematic analysis was used to assess the content of RA statements which were also mapped to the items of the MoH and WHO statements.

Gender differences in the left inferior frontal gyrus in normal children.

This study examined frontal lobe subregions in 46 normal children and adolescents (25 females, mean age: 11.08, SD: 3.07; and 21 males, mean age: 10.