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Rasagiline mesylate (RM) is a monoamine oxidase inhibitor that is commonly used to alleviate the symptoms of Parkinson’s disease. However, it suffers from low oral bioavailability due to its extensive hepatic metabolism in addition to its hydrophilic nature which limits its ability to pass through the blood–brain barrier (BBB) and reach the central nervous system where it exerts its pharmacological effect. Thus, this study aims to form RM-loaded spanlastic vesicles for intranasal (IN) administration to overcome its hepatic metabolism and permit its direct delivery to the brain. RM-loaded spanlastics were prepared using thin film hydration (TFH) and modified spraying technique (MST). A 2 3 factorial design was constructed to study and optimize the effects of the independent formulation variables, namely, Span type, Span: Brij 35 ratio, and sonication time on the vesicles᾽ characteristics in each preparation technique. The optimized system prepared using MST (MST 2) has shown higher desirability factor with smaller PS and higher EE%; thus, it was selected for further in vivo evaluation where it revealed that the extent of RM distribution from the intranasally administered spanlastics to the brain was comparable to that of the IV drug solution with significantly high brain-targeting efficiency (458.47%). These results suggest that the IN administration of the optimized RM-loaded spanlastics could be a promising, non-invasive alternative for the efficient delivery of RM to brain tissues to exert its pharmacological activities without being dissipated to other body organs which subsequently may result in higher pharmacological efficiency and better safety profile. Graphical Abstract

PurposeGallic acid (GA) is a polyphenolic compound with proven efficacy against hepatic fibrosis in experimental animals. However, it suffers from poor bioavailability and rapid clearance that hinders its clinical investigation. Accordingly, we designed and optimized reverse micelle-loaded lipid nanocapsules (RMLNC) using Box-Behnken design that can deliver GA directly into activated-hepatic stellate cells (aHSCs) aiming to suppress hepatic fibrosis progression.MethodsGA-RMLNC was prepared using soft energy, solvent free phase inversion temperature method. Effects of formulation variables on particle size, zeta potential, entrapment efficiency (EE%) and GA release were studied. In-vivo biodistribution of GA-RMLNC in rats and in-vitro activities on aHSCs were also explored.ResultsNano-sized GA-RMLNCs (30.35 ± 2.34 nm) were formulated with high GA-EE% (63.95 ± 2.98% w/w) and physical stability (9 months). The formulated system showed burst GA release in the first 2 h followed by sustained release profile. In-vivo biodistribution imaging revealed that RMLNC-loaded with rhodamine-B accumulated mainly in rats’ livers. Relative to GA; GA-RMLNC displayed higher anti-proliferative activities, effective internalization into aHSCs, marked down-regulation in pro-fibrogenic biomarkers’ expressions and elevated HSCs’ apoptosis.ConclusionsThese findings emphasize the promising application of RMLNC as a delivery system in hepatic fibrosis treatment, where successful delivery of GA into aHSCs was ensured via increased cellular uptake and antifibrotic activities.

Zein/phospholipid composite nanoparticles (CNPs) were developed as a delivery platform for gallic acid (GA), a polyphenolic compound with reported preclinical antifibrotic activities. However, the therapeutic applicability of GA is hampered owing to its low bioavailability and rapid clearance. Accordingly, we developed GA-loaded CNPs. The effect of their size, surface charge and targeting strategies was investigated and optimized, with the aim of enhancing their ability to deliver GA to the activated hepatic stellate cells (aHSCs) in order to suppress hepatic fibrosis progression. Different CNP systems were prepared and characterized with regard to their particle size, zeta potential, and GA entrapment efficiency (EE%). Also, they were statistically optimized via response surface methodology. The optimized systems were investigated with regard to their in vitro GA release, in vitro efficacy on aHSCs, and in vivo biodistribution in healthy rats. The GA-loaded cationic CNPs coupled with vitamin A (GA-CACNP/VA; 192 nm) showed high GA EE% (60% w/w), highest cellular internalization via active targeting, and more selective hepatic distribution, relative to free GA solution, GA-loaded anionic, and GA-loaded cationic systems. Furthermore, GA-CACNP/VA markedly triggered the apoptosis of aHSCs, repressed collagen deposition, and inhibited HSCs' activation to a lesser extent. The GA-CACNP/VA was shown to be a promising candidate for specific and controlled delivery of GA to aHSCs, which may provide an effective antifibrotic therapeutic approach.

This erratum is to correct the name of the moiety responsible for the negativity of Lipoid S75.