Mild, Organo-Catalysed Borono-Deamination as a Key to Late-Stage Pharmaceutical Precursors and 18F-Labelled Radiotracers.

A tris(pentafluorophenyl)borane catalysed method for the synthesis of boronic acid esters from aromatic amines in yields of up to 93% was devised. Mild conditions, benign reagents, short reaction times, low temperatures and a wide substrate scope characterize the method. The reaction was found applicable to the synthesis of boronic acid ester derivatives of complex drug molecules in up to 86% isolated yield and high purity suitable for labelling. These boronates were subsequently labelled with [18F]fluoride ion in radiochemical yields of up to 55% with and even without isolation of the boronate-intermediate.

Comparative Study of the SEM Evaluation, EDX Assessment, Morphometric Analysis, and Cyclic Fatigue Resistance of Three Novel Brands of NiTi Alloy Endodontic Files.

In this study, we compare and analyze the scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), morphometry and cyclic fatigue resistance of Endogal, PathMax, and Smarttrack novel brands of nickel−titanium (NiTi) alloy endodontic files. Material and Methods: Thirty sterile NiTi endodontic rotary files were randomly selected and assigned to one of the following study groups: A: 25.08 F2 Endogal (EDG) (n = 10); B: 25.08 F2 Path Max Pro (PMP) (n = 10); and C: 25.06 Smarttrack (ST) (n = 10). Dynamic cyclic fatigue tests were conducted using a cyclic fatigue device in stainless steel artificial root canal systems with an apical diameter of 250 µm, curvature angle of 60°, radius of curvature of 3 mm, and taper of 6%. Additionally, we analyzed the NiTi endodontic rotary files using EDX, SEM, and morphometry after micro-CT scanning. The results were analyzed using Weibull statistical analysis and ANOVA testing. Results: SEM, EDX, and morphometric analyses showed differences between the three novel brands of NiTi endodontic rotary files. Moreover, statistically significant differences were observed between the number of cycles to failure and time to failure of the three novel brands of NiTi endodontic rotary files (p < 0.001). Conclusions: Smarttrack NiTi alloy endodontic reciprocating files display greater resistance to cyclic fatigue than Endogal and Path Max Pro NiTi alloy endodontic rotary files, due to the reciprocating movement and metallurgical composition.

Formulation development and upscaling of lipid nanocapsules as a drug delivery system for a novel cyclic GMP analogue intended for retinal drug delivery.

Lipid nanocapsules (LNCs) were prepared with a novel cyclic GMP analogue, DF003, intended for the treatment of neurodegenerative retinal degenerations. LNCs loaded with DF003 were prepared by a phase inversion method and characterized for particle size, polydispersity index, drug loading, entrapment efficiency, stability, and in vitro drug release. Particle size, PdI and zeta potential of selected optimized formulation were 76 ± 1.2 nm, 0.16 ± 0.02, and -11.6 ± 0.4 mV, respectively, with an entrapment efficiency of 69 ± 0.5%. The selected formulation showed a sustained drug release for up to 6 days in phosphate buffer as well as in vitreous components. Stability evaluation of LNCs in presence of vitreous components demonstrated structural stability and compatibility. Further, the nanoparticle preparation process was upscaled to 1000 times (10 L) of the typical lab scale (0.01 L). Product parameters were observed to be unaffected by the upscaling, demonstrating that the LNCs were of the same quality as those prepared at lab scale. Additionally, the manufacturing process was adapted and assessed for a continuous production of LNCs to leverage it for industrial viability. Overall, these findings reveal the remarkable potential of LNCs as drug delivery vehicles and their possibility for clinical translation.

Efficient Delivery of Hydrophilic Small Molecules to Retinal Cell Lines Using Gel Core-Containing Solid Lipid Nanoparticles.

In this study, we developed a novel solid lipid nanoparticle (SLN) formulation for drug delivery of small hydrophilic cargos to the retina. The new formulation, based on a gel core and composite shell, allowed up to two-fold increase in the encapsulation efficiency. The type of hydrophobic polyester used in the composite shell mixture affected the particle surface charge, colloidal stability, and cell internalization profile. We validated SLNs as a drug delivery system by performing the encapsulation of a hydrophilic neuroprotective cyclic guanosine monophosphate analog, previously demonstrated to hold retinoprotective properties, and the best formulation resulted in particles with a size of ±250 nm, anionic charge > -20 mV, and an encapsulation efficiency of ±60%, criteria that are suitable for retinal delivery. In vitro studies using the ARPE-19 and 661W retinal cell lines revealed the relatively low toxicity of SLNs, even when a high particle concentration was used. More importantly, SLN could be taken up by the cells and the release of the hydrophilic cargo in the cytoplasm was visually demonstrated. These findings suggest that the newly developed SLN with a gel core and composite polymer/lipid shell holds all the characteristics suitable for the drug delivery of small hydrophilic active molecules into retinal cells.