Design of biodegradable bi-compartmental microneedles for the stabilization and the controlled release of the labile molecule collagenase for skin healthcare

Polymeric microneedles (MNs) have emerged as a novel class of drug delivery system thanks to their ability in penetrating the skin with no pain, encapsulate active proteins and in particular, proposed bicompartimental MNs can tune protein release.

A conceptual approach to the formation of paramagnetic nanospecies of noble metals

The general concepts are analyzed regarding the approach for the formation of paramagnetic species of noble metals, with a non-rigid (labile) molecule being used as a supporting matrix. The formation of the metal nanospecies follows three stages: (i) the metal ions are captured by the matrix, (ii) the reducing agent causes formation of individual atoms separated by the matrix fragments, (iii) the individual atoms agglomerate due to conformational transformations of the labile molecule-matrix. This algorithm is realized in two distinct systems: Ag-containing nanospecies embedded within the system of polyacrylic acid (PAA) chains grafted to the film of fluorinated ethylene propylene copolymer (FEP) and Au-containing nanospecies in the free matrix of tannin-citrate- oxo-hydroxo aluminate. The evolution of the electron paramagnetic resonance (EPR) spectra while cooling down demonstrates the appearance of the exchange interaction which is suppressed at higher temperatures by the vibrational modes of the molecule-matrix. The role of the oxo-hydroxo aluminate form is one of a molecular motor sorting the individual nanospecies by their size and charge state.

Nitric Oxide Synthase in Diabetic Retinopathy in the BBZ/WOR Rat: An Immunocytochemical Study

Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to citrulline and the highly reactive free radical species, NO. Two major constitutive isoforms, neuronal and endothelial NOS, have been ented in the retina. These constitutive isoforms produce small amounts of NO while the inducible isoform, iNOS, produces high levels of NO. Excess production of NO by iNOS has beem implicated in the complications of diabetes. Since NO is a highly labile molecule, its potential localization is best achieved by immunocytochemical studies of NOS.Semiquantitative colloidal gold labeled immunocytochemical studies of endothelial NOS (eNOS) and iNOS were done on sections of neural retina in eyes of obese, noninsulin dependent diabetic BBZ/Wor rats with diabetes of five months to twelve months duration. Age matched, nondiabetic control retinas were from eyes from BBDR/Wor rats.Levels of iNOS were elevated in diabetic (33.9 ± 10.0 gold particles) as compared to age matched nondiabetic control (3.5 ± 2.8 gold particles) retinas.

The structural basis for neutrophil inactivation of C1̅ inhibitor

Limited proteolysis of C1 inhibitor (C1-INH) by neutrophil elastase, Pseudomonas elastase and snake venoms resulted in initial cleavage within the molecule's N-terminus followed by further cleavage within the molecule's C-terminally placed reactive centre. N-Terminal proteolysis occurred at peptide bonds 14-15, 36-37 and 40-41. This had no effect on either the inhibitory activity or the heat-stability of C1-INH. Proteolysis within the reactive centre occurred at peptide bonds 439-440, 440-441, 441-442 and 442-443. Cleavage at any one of these sites inactivated C1-INH and conferred enhanced heat-stability upon a previously heat-labile molecule. Released neutrophil proteinases also cleaved and inactivated C1-INH, suggesting that they may physiologically regulate C1-INH during inflammatory episodes.