Role of self‐assembly conditions and amphiphilic balance on nanoparticle formation of PEG‐PDLLA copolymers in aqueous environments

The production of well‐defined and reproducible polymeric nanoparticles (NPs), in terms of size and stability in biological environments, is undoubtedly a fundamental challenge in the formulation of novel and more effective nanomedicines. The adoption of PEGylated lactide (LA) block copolymers as biodegradable and biocompatible nanocarriers at different clinical stages has rendered these materials an attractive polymeric platform to be exploited and their formulation is further understood. In the present work, we synthesized a library of linear polyethylene glycol‐poly(D,L‐lactide) block copolymers with different lengths of LA (15, 25, 50, and 100 LA units) via simple and metal‐free ring‐opening polymerization, in order to alter the amphiphilic balance of the different macromolecules. The produced polymers were formulated into NPs while varying a series of key parameters in the solvent displacement process, including solvent:nonsolvent ratios and the nature of the two media, and the effect on size and stability was assessed. In addition, stability to protein–NPs interaction and aggregation was studied, highlighting the different NP final properties according to the nature of the amphiphilic balance and nanoformulation conditions. Therefore, we have illustrated a systematic and methodological process to optimize a series of NPs parameters balancing particle size, size distribution, surface charge, and stability to guide future works in the nanoformulation field. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 1801–1810     

Enhancing Dual-State Emission in Maleimide Fluorophores through Fluorocarbon Functionalisation

Herein, a library of trifluoroethyl substituted aminomaleimide derivatives are reported with small size and enhanced emissions in both solution and solid-state. A diCH₂CF₃ substituted aminochloromaleimide exhibits the most efficient dual-state emission (Φ_f >50 % in solution and solid-state), with reduced quenching from protic solvents. This is attributed to the reduction of electron density on the maleimide ring and suppressed π-π stacking in the solid-state. This mechanism was explored in-depth by crystallographic analysis, and modelling of the electronic distribution of HOMO-LUMO isosurfaces and NCI plots. Hence, these dual-state dyes overcome the limitations of single-state luminescence and will serve as an important step forward for this rapidly developing nascent field.     

Inversion of analytically perturbed linear operators that are singular at the origin

Let H and K be Hilbert spaces and for each z∈C let A(z)∈L(H,K) be a bounded but not necessarily compact linear map with A(z) analytic on a region |z|<a. If A(0) is singular we find conditions under which A⁻¹(z) is well defined on some region 0<|z|<b by a convergent Laurent series with a finite order pole at the origin. We show that by changing to a standard Sobolev topology the method extends to closed unbounded linear operators and also that it can be used in Banach spaces where complementation of certain closed subspaces is possible. Our method is illustrated with several key examples.²     

anti-Tuberculosis natural products: synthesis and biological evaluation of pyridoacridine alkaloids related to ascididemin

There is an urgent need for novel therapeutics possessing new modes of action to treat tuberculosis (TB) infections. In this study we report on the synthesis and biological evaluation of a series of pyrido[2,3,4-kl]acridin-6-one alkaloids related to the anti-TB (MIC 0.35 μM) but cytotoxic (IC₅₀ <0.14 μM) marine natural product ascididemin (1). The most interesting compounds identified were 21 and 24, which were found to inhibit the growth of Mycobacterium tuberculosis (Mtb) H₃₇Rv with MIC 2.0 μM, but with negligible cytotoxicity towards Vero and P388 cells (IC₅₀>25 μM). Another analogue (10) was evaluated against a range of singly-drug-resistant strains of Mtb and was found to exhibit no cross-resistance. These results suggest that the pyrido[2,3,4-kl]acridin-6-one skeleton may provide a useful scaffold for future studies directed towards possible anti-TB drugs.     

On Nonlinear Operator Approximation with Preassigned Accuracy

In this paper, we provide a state-of-the-art survey of some recent methods in nonlinear operator approximation theory and its applications. We give existence theorems for approximating operators. and discuss corresponding numerical schemes. The new results are natural but very specific extensions of known techniques to the so-called realistic operator approximation.     

Polymers containing fluorinated ketone groups. III. Synthesis of styrene/p-vinyltrifluoroacetophenone copolymers by modification of polystyrene and the copolymerization of monomers

Copolymers of styrene/p-vinyltrifluoroacetophenone were prepared by two different reaction routes: (1) modification of polystyrene with trifluoroacetyl chloride and (2) copolymerization of styrene and p-vinyltrifluoroacetophenone (VTFA). There appears to be a limit to the modification method because only a maximum content of 14.5 mole % trifluoroacetyl functionality could be attached to the polymer before the onset of crosslinking. Differential scanning calorimetry (DSC) was used to determine their T_g's. In addition, the reactivity ratios of styrene and VTFA were investigated. The reactivity ratios and Q and e values were r₁ = 0.30 ± 0.09 (styrene) and r₂ = 1.3 ± 0.3 (VTFA); Q₁ = 1.0 and e₁ = ?0.8 (styrene); Q₂ = 0.44 and e₂ = 1.93 (VTFA).     

Effect of surface composition on the flowability of industrial spray-dried dairy powders

The surface composition of four industrial spray-dried dairy powders (skim milk powder, whole milk powder, cream powder and whey protein concentrate) was estimated by electron spectroscopy for chemical analysis (ESCA), and its influence on powder flowability was studied. It was found that skim milk powder flows well compared to the other powders because the surface is made of lactose and protein with a small amount of fat, whereas the high surface fat composition inhibits the flow of whole milk, cream and whey protein powders. However, the poor flowability of the powders with high surface fat coverage was drastically improved by removal of fat present on the surface through a brief wash with petroleum ether. The results obtained indicate that, although there are several parameters including particle size, which influence the flowability of powders, the flowability of powders is strongly influenced by the surface composition of powders, particularly for fat-containing powders.     

Melting characteristics of fat present on the surface of industrial spray-dried dairy powders

The melting characteristics of the fat present on the surface (surface free-fat) of two industrial spray-dried dairy powders (cream powder and whole milk powder) were investigated in comparison with those of other milk fat fractions present in the powder, such as free-fat from the interior of the powder particle (inner free-fat) and encapsulated fat. The melting characteristics of the milk fat fractions were studied by fatty acid composition, melting profile and solid fat content profile. The results indicated that all milk fat fractions including surface free-fat contained various triglycerides with melting points ranging from -40 to +40 degrees C. However, some fractionation was observed among the different milk fat fractions. The free-fat fractions (surface free-fat and inner free-fat) had a greater proportion of high-melting triglyceride species than the encapsulated fat. Furthermore, the high-melting triglyceride species present in the free-fat fractions were slightly accumulated at the surface of powder. This phenomenon was observed in both cream powder and whole milk powder and its effect on wetting time was established. This indicates that manipulation of the surface fat content during drying operation may hold the key to functionality improvement.