Franklin Muñoz-Muñoz

Mucoadhesive thermo-responsive chitosan-g-poly(N-isopropylacrylamide) polymeric micelles via a one-pot gamma-radiation-assisted pathway

Thermo-sensitive graft copolymer amphiphiles of chitosan (CS) and poly(N-isopropylacrylamide) (PNiPAAm), CS-g-PNIPAAm, were successfully synthesized by a catalyst-less one-pot gamma (γ)-radiation-assisted free radical polymerization at three different radiation doses: 5, 10 and 20 kGy. The chemical structure of the copolymers was confirmed by FTIR and solid-state (13)C NMR and the grafting extent by (1)H NMR and gravimetric analysis. In general, the higher the dose, the smaller the grafting due to the more significant NiPAAm homopolymerization. Due to the grafting of poly(NiPAAm) blocks, aqueous solutions of the different copolymers underwent a sharp transition upon heating above 32 °C, the characteristic lower critical solution temperature (LCST) of poly(NiPAAm). Then, the critical micellar concentration (CMC), the size and size distribution and the zeta-potential were characterized by dynamic light scattering (DLS) and the polymeric micelles visualized in suspension and quantified by Nanoparticle Tracking Analysis (NTA), at 37 °C. CMC values were in the 0.0012-0.0025%w/v range and micelles displayed sizes between 99 and 203 nm with low polydispersity (<0.160) and highly positive zeta-potential (>+15 mV) that suggested the partial conservation of the amine groups upon NiPAAm grafting. Consequently, polymeric micelles displayed the intrinsic mucoadhesiveness of CS, as established in vitro by the mucin solution assay. Finally, the encapsulation capacity of the micelles was assessed with the highly hydrophobic protease inhibitor antiretroviral indinavir free base (IDV). Polymeric micelles led to a significant 24-fold increase of the aqueous solubility from 63 μg/mL to 1.45 mg/mL, a performance remarkably better than different poly(ethylene oxide)-b-poly(propylene oxide) block copolymers assessed before. Overall results highlight the potential of this nanotechnology platform to expand the application of polymeric micelles to mucosal administration routes.

Optimal sidewall functionalization for the growth of ultrathin TiO2 nanotubes via atomic layer deposition

One of the most suitable approaches for the production of inorganic nanotubes is by means of carbon nanotube (CNT) templates coated by atomic layer deposition (ALD). This approach is attractive because it has the potential of controlling the wall thickness down to the Angstroms level. However, it is a recognized fact that the chemistry of the substrate surface can delay the full coverage at the initial stages of the ALD coating process, mainly due to nucleation issues. This is an important issue that might restrict laying down homogeneous coatings within the ultrathin range, which is the foundation for producing self-supported inorganic nanotubes. Here, we explore the early stage of the TiO2 nucleation on CNT templates systematically functionalized with different chemical groups (COOH, OH) or N-doped. The effects of the functionalization on the nucleation process from tetrakis (dimethylamino) titanium and water were meticulously studied by means of transmission electron microscopy. Observations revealed grain-like growth of TiO2 over pristine, purified and –OH-functionalized CNTs. In contrast, COOH functionalization yielded good conformality, which was improved on N-doped CNTs. Results were confirmed by X-rays photoelectron spectroscopy analysis. We recommend either COOH or N-doped CNTs for the production of ultrathin TiO2 nanotubes.

An agent-based model of the fission yeast cell cycle

The objective of this paper is to develop a computational model of the fission yeast (Schizosaccharomyces pombe) cell cycle using agent-based modeling (ABM), to study the sequence of states of the proteins and time of the cell cycle phases, under the action of proteins that regulate its cell cycle. The model relies only on the conceptual model of the yeast cell cycle regulatory network, where each protein has been represented as an agent with a property called activity that represents its biological function and a stochastic Brownian movement. The results indicate that the simulated phase time did have similar results in comparison with other models using mathematical approaches. Similarly, the correct sequence of states was achieved, and the model was run under different initial states to understand its emergent behaviors. The cell reached the G1 stationary state 94% of the times when running the model under biological initial conditions and 87% of the times when running the model through all the different combinations of initial states. Such results imply that the cell was capable to fix toward the biological expected phenomena. These results show that ABM is a suitable technique to study protein–protein interactions without using, often unavailable, kinetic parameters, or differential equations. This model sets as a base for further studies that involve the cell cycle of the fission yeast, with a special attention to studies and development of drug treatments for specific types of cancer.