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.

S-Protected Thiolated Chitosan versus Thiolated Chitosan as Cell Adhesive Biomaterials for Tissue Engineering.

Chitosan (Ch) and different Ch derivatives have been applied in tissue engineering (TE) because of their biocompatibility, favored mechanical properties, and cost-effectiveness. Most of them, however, lack cell adhesive properties that are crucial for TE. In this study, we aimed to design an S-protected thiolated Ch derivative exhibiting high cell adhesive properties serving as a scaffold for TE.

Smartwatch-derived heart rate variability: a head-to-head comparison with the gold standard in cardiovascular disease.

Aims: We aimed to investigate the concordance between heart rate variability (HRV) derived from the photoplethysmographic (PPG) signal of a commercially available smartwatch compared with the gold-standard high-resolution electrocardiogram (ECG)-derived HRV in patients with cardiovascular disease.

Methods And Results: We prospectively enrolled 104 survivors of acute ST-elevation myocardial infarction, 129 patients after an ischaemic stroke, and 30 controls. All subjects underwent simultaneous recording of a smartwatch (Garmin vivoactive 4; Garmin Ltd, Olathe, KS, USA)-derived PPG signal and a high-resolution (1000 Hz) ECG for 30 min under standardized conditions.

Replacing PEG-surfactants in self-emulsifying drug delivery systems: Surfactants with polyhydroxy head groups for advanced cytosolic drug delivery.

Aim: Evaluation of different polyhydroxy surfaces in SEDDS to overcome the limitations associated with conventional polyethylene glycol (PEG)-based SEDDS surfaces for intracellular drug delivery.

Methods: Anionic, cationic and non-ionic polyglycerol- (PG-) and alkylpolyglucoside- (APG-) surfactant based SEDDS were developed and compared to conventional PEG-SEDDS. Particular emphasis was placed on the impact of SEDDS surface decoration on size and zeta potential, drug loading and protective effect, mucus diffusion, SEDDS-cell interaction and intracellular delivery of the model drug curcumin.

In Vitro Investigation of Thiolated Chitosan Derivatives as Mucoadhesive Coating Materials for Solid Lipid Nanoparticles.

In the present study, chitosan (CS) was thiolated by introducing l-cysteine via amide bond formation. Free thiol groups were protected with highly reactive 6-mercaptonicotinic acid (6-MNA) and less-reactive l-cysteine, respectively, via thiol/disulfide-exchange reactions. Unmodified CS, l-cysteine-modified thiolated CS (CS-Cys), 6-MNA-S-protected thiolated CS (CS-Cys-MNA), and l-cysteine-S-protected thiolated CS (CS-Cys-Cys) were applied as coating materials to solid lipid nanoparticles (SLN).

Size shifting of solid lipid nanoparticle system triggered by alkaline phosphatase for site specific mucosal drug delivery.

We aim to prepare a size-shifting nanocarrier for site-targeting mucosal drug delivery that can penetrate through mucus gel layer and remain close to the absorption membrane. As nanocarriers can be engineered to penetrate mucus but they can also back diffuse into outer mucus regions, a size shifting to micron range once they have reached the absorption membrane would prevent back-diffusion effect and extend drug release over a long period of time. For this purpose, we loaded solid lipid nanoparticles (SLN) with a phosphate ester surfactant and octadecylamine.

Charge reversal self-emulsifying drug delivery systems: A comparative study among various phosphorylated surfactants.

Hypothesis: Phosphorylated surfactants having ethoxylate spacer arms are promising excipients for charge reversal self-emulsifying drug delivery systems (SEDDS).

Experiments: 1,2-Dipalmitoyl-sn-glycero-3-phosphatidic acid disodium salt (PA), 2-((2,3-bis(oleoyloxy)propyl)dimethylammonio)ethyl hydrogen phosphate (DOCP), nonylphenol monophosphate ester (PNPP), C12-15 alcohol 3 ethoxylate phosphate ester (PME) and polyoxyethylene (9) dioctanoyl glycerol pyrophosphate (DGPP) loaded SEDDS were developed and characterized. Zeta potential of SEDDS was measured before and after incubation with intestinal alkaline phosphatase (IAP).

Polyphosphate coatings: A promising strategy to overcome the polycation dilemma.

Aim: It was the aim of this study to develop a zeta potential changing drug delivery system by decorating lipid-based nanocarriers with a polycationic cell penetrating peptide (CPP) and subsequently masking these cationic substructures with polyphosphates.

Methods: In order to anchor the CPP poly-l-lysine (PLL) on the surface of the oily droplets of an o/w nanoemulsion, stearic acid was covalently attached to the peptide. The resulting CPP-decorated oily droplets were coated with phytic acid and tripolyphosphate.

Impact of bile salts and a medium chain fatty acid on the physical properties of self-emulsifying drug delivery systems.

The aim of this study was the evaluation of the influence of bile salts and fatty acids, important components of intestinal fluids, on physical characteristics of self-emulsifying drug delivery systems (SEDDS) such as size, polydispersity (PDI), zeta potential (Zp), turbidity (T%), cloud point temperature (CPT) and drug release. At this purpose, nonionic (ni-SEDDS) and cationic (c-SEDDS) were emulsified in aqueous media containing increasing concentrations of bile salts (BS) and decanoate (Dec). Zp of ni-SEDDS and c-SEDDS became highly negative at 15 mM BS and Dec.

Cellular uptake of self-emulsifying drug-delivery systems: polyethylene glycol versus polyglycerol surface.

Comparison of the impact of polyethylene glycol (PEG) and polyglycerol (PG) surface decoration on self-emulsifying drug delivery system (SEDDS)-membrane interaction and cellular uptake.   PEG-, PEG/PG- and PG-SEDDS were assessed regarding their self-emulsifying properties, surface charge, bile salt fusibility, cellular uptake and interaction with endosome-mimicking membranes. SEDDS exhibited droplet sizes between 150 and 175 nm, a narrow size distribution and self-emulsified within 7 min.

Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring.

Aim: The aim of this study was to evaluate biodegradable cationic surfactants based on lysine.

Methods: Lysine was esterified with cholesterol, oleyl alcohol and 1-decanol resulting in cholesteryl lysinate (CL), oleyl lysinate (OL) and decyl lysinate (DL). Esters were investigated regarding their log D, critical micelle concentration (CMC) and biodegradability.

Strategies for improved hair binding: Keratin fractions and the impact of cationic substructures.

Keratin extracts and hydrolysates from varying sources, their chemical modifications and compositions thereof have shown potential in the restoration of hair properties. Within this study on reactivity of thiol groups and the shielding effect of anionic charges the binding of keratin-associated proteins (KAP) and α-keratins (Ker) extracted from human hair to natural and permed hair fibers was evaluated. Selectively extracted KAP and Ker were preactivated with 6-mercaptonicotinamide in a quantity of 194 ± 21 μmol/g for KAP and 169 ± 27 μmol/g for Ker resulting in 1.

Zeta potential changing nanoemulsions: Impact of PEG-corona on phosphate cleavage.

The aim of this study was to evaluate the impact of a PEG-corona on oily droplets of a nanoemulsion on phosphate cleavage on their surface. A PEG-free nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85 being additionally stabilized by 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) was evaluated regarding phosphate release, zeta potential change and mucus permeation properties. In order to evaluate the impact of PEG-corona on phosphate release 10%, 20% and 30% of polyethoxylated-35 castor oil were incorporated in the nanoemulsion.

Grafting of wool fibers through disulfide bonds: An advanced application of S-protected thiolated starch.

The purpose of this study is to develop a potential pathway for grafting polymers onto wool fibers based on thiol-disulfide exchange reactions. S-protected thiolated starch (PTS) was synthesized by coupling 3-(2-pyridyldithio) propanoic acid to starch through esterification, resulting in 417.3 ± 15.

Highly mucus permeating and zeta potential changing self-emulsifying drug delivery systems: A potent gene delivery model for causal treatment of cystic fibrosis.

Aim: It was the aim of the study to develop self-emulsifying drug delivery systems (SEDDS) with the ability to change their zeta potential towards higher values at the adsorption membrane and in this way facilitate the release of the DNA-cetrimonium complex and enhance transfection.

Methods: Plasmid DNA was complexed via hydrophobic ion pairing utilizing various surfactants and the complex was incorporated into SEDDS achieving a payload of 1% (m/v). Log P of the complex was determined.

Development and in vitro evaluation of a self-emulsifying drug delivery system (SEDDS) for oral vancomycin administration.

The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the glycopeptide antibiotic vancomycin (VAN) with improved intestinal mucosa permeating properties in order to increase oral drug absorption. VAN was effectively incorporated into SEDDS increasing the lipophilicity of the drug via hydrophobic ion pairing (HIP) with cetyltrimethylammonium bromid (CTAB). Newly developed SEDDS formulations containing VAN/CTAB complex were characterized with respect to droplet size, polydispersity index and zeta potential.

Reactive keratin derivatives: A promising strategy for covalent binding to hair.

Hypothesis: Restoration of damaged hair structure by replacing lost keratin is still of paramount interest. On account of the fact that native keratin is a highly cross-linked protein with numerous disulfide bonds but just a few nucleophilic thiol groups, binding affinity to hair is comparatively low. Hence, the design of reactive keratin derivatives bearing free sulfhydryl groups that are optionally S-protected and preactivated should enhance permanent binding to hair fibers.

Development of self-emulsifying drug delivery systems (SEDDS) for ciprofloxacin with improved mucus permeating properties.

The aim of this study was to develop a self-emulsifying drug delivery system (SEDDS) containing the fluoroquinolone antibiotic ciprofloxacin (CIP) exhibiting highly mucus permeating properties and antimicrobial activity in in vitro models. Various SEDDS formulations were developed and evaluated regarding droplet size, polydispersity index, zeta potential and formulation stability. Furthermore, SEDDS permeating properties were investigated in porcine intestinal mucus, as well as in cystic fibrosis (CF) sputum freshly collected from CF patients using Transwell® setup and single particle tracking (SPT), respectively.