Design of Nanohydrogels for Targeted Intracellular Drug Transport to the Trans-Golgi Network.

Nanohydrogels combine advantages of hydrogels and nanoparticles. In particular, they represent promising drug delivery systems. Nanogel synthesis by oxidative condensation of polyglycidol prepolymers, that are modified with thiol groups, results in crosslinking by disulfide bonds. Hereby, biomolecules like the antidiabetic peptide RS1-reg, derived from the regulatory protein RS1 of the Na+ -D-glucose cotransporter SGLT1, can be covalently bound by cysteine residues to the nanogel in a hydrophilic, stabilizing environment. After oral uptake, the acid-stable nanogels protect their loading during gastric passage from proteolytic degradation. Under alkaline conditions in small intestine the nanohydrogels become mucoadhesive, pass the intestinal mucosa and are taken up into small intestinal enterocytes by endocytosis. Using Caco-2 cells as a model for small intestinal enterocytes, by confocal laser scanning microscopy and structured illumination microscopy, the colocalization of fluorescent-labeled RS1-reg with markers of endosomes, lysosomes, and trans-Golgi-network after uptake with polyglycidol-based nanogels formed by precipitation polymerization is demonstrated. This indicates that RS1-reg follows the endosomal pathway. In the following, the design of bespoken nanohydrogels for specific targeting of RS1-reg to its site of action at the trans-Golgi network is described that might also represent a way of targeted transport for other drugs to their targets at the Golgi apparatus.

Covalently Cross-Linked Pig Gastric Mucin Hydrogels Prepared by Radical-Based Chain-Growth and Thiol-ene Mechanisms.

Mucin, a high molecular mass hydrophilic glycoprotein, is the main component of mucus that coats every wet epithelium in animals. It is thus intrinsically biocompatible, and with its protein backbone and the o-glycosidic bound oligosaccharides, it contains a plethora of functional groups which can be used for further chemical modifications. Here, chain-growth and step-growth (thiol-ene) free-radical cross-linked hydrogels prepared from commercially available pig gastric mucin (PGM) are introduced and compared as cost-efficient and easily accessible alternative to the more broadly applied bovine submaxillary gland mucin. For this, PGM is functionalized with photoreactive acrylate groups or allyl ether moieties, respectively. Whereas homopolymerization of acrylate-functionalized polymers is performed, for thiol-ene cross-linking, the allyl-ether-functionalized PGM is cross-linked with thiol-functionalized hyaluronic acid. Morphology, mechanical properties, and cell compatibility of both kinds of PGM hydrogels are characterized and compared. Furthermore, the biocompatibility of these hydrogels can be evaluated in cell culture experiments.

Impact of Pre- and Intraoperative Factors on Endothelial Cell Density in the Early and Late Stage after Penetrating Keratoplasty. / Prä- und intraoperative Einflussgrößen auf die Endothelzellentwicklung in der Früh- und Spätphase nach perforierender Keratoplastik.

AIM: This retrospective investigated the impact of donor age, recipient age, donor endothelial cell density, vis-à-tergo, and additional intraoperative lens exchange (triple-procedure) on overall early and late phase postoperative endothelial cell density (ECD) following penetrating keratoplasty (PKP) in various diagnosis groups. PATIENTS AND METHODS: In 590 cases with diagnosed keratoconus (KC), Fuchs dystrophy (FD) and herpes simplex virus infection (HSV) who underwent PKP or triple surgery, the ECD in cells/mm2 was analysed, both preoperatively, with all-sutures-in (early postoperative stage), and after last suture removal. The factors were tested by Mann-Whitney U-test, correlation analysis and linear regression analysis. OUTCOME: Correlation analysis demonstrated a weak negative correlation between the patient's ECD and donor age (early postoperative stage: r = - 0.25, p < 0.001; after last suture removal: r = - 0.16; p = 0.003). Regression analysis revealed that donor age did not impact postoperative patient ECD. There was a weak negative correlation between postoperative ECD and recipient age (early postoperative stage: r = - 0.31, p < 0.001; after last suture removal: r = - 0.34, p < 0.001). Regression analysis confirmed the negative impact of recipient age on patient ECD (early postoperative stage: ß = - 13.2, p = 0.001; after last suture removal: ß = - 4.6, p < 0.001). Correlation analysis determined a weak positive correlation between postoperative ECD and donor endothelial cell density (early postoperative stage: r = 0.37, p < 0.001; after last suture removal: r = 0.32, p < 0.001). Regression analysis also determined that donor endothelial cell density had a positive impact on postoperative ECD following last suture removal (ß = 0.4, p < 0.001). Vis-à-tergo and additional lens exchange (triple procedure) had no significant effect on postoperative ECD (p > 0.05). This was also confirmed by the results of the regression analysis after last suture removal. CONCLUSION: Recipient age and donor endothelial cell density have a significant impact on postoperative ECD following PKP. Not all of the statistical tests proved donor age to be a significant influencing factor. Vis-à-tergo and additional lens exchange (triple procedure) had no significant effect on postoperative ECD following PKP.

Giant magnetic field effects in donor-acceptor triads: On the charge separation and recombination dynamics in triarylamine-naphthalenediimide triads with bis-diyprrinato-palladium(II), porphodimethenato-palladium(II), and palladium(II)-porphyrin photosensitizers.

A series of triads consisting of a triarylamine donor, a naphthalenediimide acceptor, and a palladium photosensitizer bridge was investigated for the photoinduced electron transfer processes and the spin chemistry involved. In this series, the ligand in the palladium photosensitizer was varied from bis-dipyrrinato to porphodimethenato and to a porphyrin. With the porphyrin photosensitizer, no charge separated state could be reached. This is caused by the direct relaxation of the excited photosensitizer to the ground state by intersystem crossing. The bis-dipyrrinato-palladium photosensitizer gave only a little yield (7%) of the charge separated state, which is due to the population of a metal centered triplet state and a concomitant geometrical rearrangement to a disphenoidal coordination sphere. This state relaxes rapidly to the ground state. In contrast, in the porphodimethenato-palladium triads, a long lived (µs to ms) charge separated state could be generated in high quantum yields (66%-74%) because, here, the population of a triplet metal centered state is inhibited by geometrical constraints. The magnetic field dependent transient absorption measurement of one of the porphodimethenato triads revealed a giant magnetic field effect by a factor of 26 on the signal amplitude of the charge separated state. This is the consequence of a magnetic field dependent triplet-singlet interconversion that inhibits the fast decay of the charge separated triplet state through the singlet recombination channel. A systematic comparative analysis of the spin-dependent kinetics in terms of three classical and one fully quantum theoretical methods is provided, shedding light on the pros and cons of each of them.

Review of pulmonary emboli and techniques for their mechanical removal to inform device design.

Pulmonary emboli present a significant burden of disease, with limited treatment options for some patients. Mechanical devices for pulmonary emboli removal are becoming increasingly prevalent though more work remains to be done. This paper briefly discusses the mechanical properties of pulmonary emboli, the disease state they cause, and the existing embolectomy devices. The goal of this paper is to aid the design of minimally invasive mechanical pulmonary emboli removal devices, by providing a review of this topic as well as some key design specifications.