No abstract

Measurement of adherence to highly active antiretroviral therapy is complex. Because there is no gold standard for it, we demonstrated that each of three common adherence measures has shortcomings that can be minimized in a combined measurement system. Indinavir plasma levels appear to provide no additional information, so further studies are undoubtedly necessary.

By combining the photothermal ability of copper sulphide nanoparticles (NPs) upon excitation with Near Infrared (NIR) Light and the thermo-responsive properties of the homemade oligo (ethylene glycol) methyl ether methacrylate copolymer we have obtained fragmentable nanocomposites able to release a carried drug on-demand after NIR-light triggering. A complete physico-chemical characterization of the resulting nanoparticles has been carried out and their degradation assessed at different temperatures. Herein, we have also evaluated the drug loading capacity of those nanoparticles and the temperature dependence in their drug release kinetics using bupivacaine hydrochloride as a model drug. For those hybrid nanoparticles, subcytotoxic doses on four different cell lines and their potential interference in cell metabolism, induction of apoptosis, and cell cycle have been evaluated by Alamar Blue fluorometry and flow cytometry.

Hybrid linear–dendritic block copolymers (LDBCs) having dendrons with a precise number of peripheral groups that are able to supramolecular bind functional moieties are challenging materials as versatile polymeric platforms for the preparation of functional polymeric nanocarriers. PEG2k-b-dxDAP LDBCs that are based on polyethylene glycol (PEG) as hydrophilic blocks and dendrons derived from bis-MPA having 2,6-diacylaminopyridine (DAP) units have been efficiently synthesized by the click coupling of preformed blocks, as was demonstrated by spectroscopic techniques and mass spectrometry. Self-assembly ability was first checked by nanoprecipitation. A reproducible and fast synthesis of aggregates was accomplished by microfluidics optimizing the total flow rate and phase ratio to achieve spherical micelles and/or vesicles depending on dendron generation and experimental parameters. The morphology and size of the self-assemblies were studied by TEM, Cryogenic Transmission Electron Microscopy (cryo-TEM), and Dynamic Light Scattering (DLS). The cytotoxicity of aggregates synthesized by microfluidics and the influence on apoptosis and cell cycle evaluation was studied on four cell lines. The self-assemblies are not cytotoxic at doses below 0.4 mg mL–1. Supramolecular functionalization using thymine derivatives was explored for reversibly cross-linking the hydrophobic blocks. The results open new possibilities for their use as drug nanocarriers with a dynamic cross-linking to improve nanocarrier stability but without hindering disassembly to release molecular cargoes.