Polymeric premicelles as efficient lipophilic nanocarriers: extending drug uptake to the submicellar regime.

A multitechnique investigation on the self-assembly behavior of a biocompatible polymer in the high dilution regime is reported herein. The obtained results unambiguously reveal the existence of premicellar structures that may further extend the efficiency of traditional polymeric micelles as drug-delivery vehicles. Such an expansion in the excipient capacity arises from (i) the increased drug retention of submicellar assemblies due to their higher resistance to dilution and therefore to their improved circulation time and (ii) the superior carrier permeability of these premicellar aggregates as a result of their smaller size, which makes these drug vehicles more effectively targeted to the tumors through the so-called enhanced permeability and retention effect. The uptake ability of the polymeric premicelles described in this work has been tested through the use of Nile Red as drug model given its intermediate lipophilicity (log P ≈ 3-5) similar to that of potent chemotherapy agents and its microenvironment-sensitive fluorescence properties relevant for localization purposes. Thus, it has been found that an efficient drug encapsulation can be achieved under conditions well below the normally required critical micelle concentration. These results may constitute a promising strategy in order to develop new and more efficient polymeric formulations in drug delivery technology.

Schuurs-Hoeijmakers Syndrome (PACS1 Neurodevelopmental Disorder): Seven Novel Patients and a Review.

Schuurs-Hoeijmakers syndrome (SHMS) or PACS1 Neurodevelopmental disorder is a rare disorder characterized by intellectual disability, abnormal craniofacial features and congenital malformations. SHMS is an autosomal dominant hereditary disease caused by pathogenic variants in the PACS1 gene. PACS1 is a trans-Golgi-membrane traffic regulator that directs protein cargo and several viral envelope proteins. It is upregulated during human embryonic brain development and has low expression after birth. So far, only 54 patients with SHMS have been reported. In this work, we report on seven new identified SHMS individuals with the classical c.607C > T: p.Arg206Trp PACS1 pathogenic variant and review clinical and molecular aspects of all the patients reported in the literature, providing a summary of clinical findings grouped as very frequent (≥75% of patients), frequent (50-74%), infrequent (26-49%) and rare (less than ≤25%).

Palladium-catalyzed amination of aryl nonaflates.

The first detailed study of the palladium-catalyzed amination of aryl nonaflates is reported. Use of ligands 2-4 and 6 allows for the catalytic amination of electron-rich and -neutral aryl nonaflates with both primary and secondary amines. With use of Xantphos 5, the catalytic amination of a variety of functionalized aryl nonaflates resulted in excellent yields of anilines; even 2-carboxymethyl aryl nonaflate is effectively coupled with a primary alkylamine. Moderate yields were obtained when coupling halo-aryl nonaflates with a variety of amines, where in most cases the aryl nonaflate reacted in preference to the aryl halide. Overall, aryl nonaflates are an effective alternative to triflates in palladium-catalyzed C-N bond-forming processes due to their increased stability under the reaction conditions.