Retrieving the size distribution of SBA-15 mesopores from small-angle X-ray scattering data using a Monte Carlo method.

A Monte Carlo (MC) method was introduced into a state-of-the-art model used to analyse small-angle X-ray scattering (SAXS) data of SBA-15, an ordered mesoporous material with many applications. With this new procedure, referred to herein as the SBA-15+MC model, it is possible to retrieve the size distribution of the mesopores, D(r), in a free modelling approach. To achieve this, two main points were addressed: (i) based on previous implementations, the method was adapted to work with long core-shell cylinders; (ii) since the MC model requires longer processing times, strategies to speed up the calculations were developed, which included a simplified version of the original model used to analyse SAXS data of SBA-15 (referred to as the SBA-15 model) as well as the determination of several structural features from the SAXS curve prior to the fit. The new model was validated with simulated data and later used to fit experimental SAXS curves of SBA-15. The obtained results show that the SBA-15 model only works well because the mesopore size distribution of SBA-15 is narrow, whereas the new approach can be successfully used in cases where D(r) is wider and/or has a more complex profile, such as SBA-15 with expanded mesopores. Even though a specific SAXS example was chosen to prove the model, the strategies presented herein are general and suitable for inclusion in other models aimed at the analysis of SBA-15 and similar ordered mesoporous materials.

Using crystallography tools to improve vaccine formulations.

This article summarizes developments attained in oral vaccine formulations based on the encapsulation of antigen proteins inside porous silica matrices. These vaccine vehicles show great efficacy in protecting the proteins from the harsh acidic stomach medium, allowing the Peyer's patches in the small intestine to be reached and consequently enhancing immunity. Focusing on the pioneering research conducted at the Butantan Institute in Brazil, the optimization of the antigen encapsulation yield is reported, as well as their distribution inside the meso- and macroporous network of the porous silica. As the development of vaccines requires proper inclusion of antigens in the antibody cells, X-ray crystallography is one of the most commonly used techniques to unveil the structure of antibody-combining sites with protein antigens. Thus structural characterization and modelling of pure antigen structures, showing different dimensions, as well as their complexes, such as silica with encapsulated hepatitis B virus-like particles and diphtheria anatoxin, were performed using small-angle X-ray scattering, X-ray absorption spectroscopy, X-ray phase contrast tomography, and neutron and X-ray imaging. By combining crystallography with dynamic light scattering and transmission electron microscopy, a clearer picture of the proposed vaccine complexes is shown. Additionally, the stability of the immunogenic complex at different pH values and temperatures was checked and the efficacy of the proposed oral immunogenic complex was demonstrated. The latter was obtained by comparing the antibodies in mice with variable high and low antibody responses.

Insight into Nanoscale Network of Spray-Dried Polymeric Particles: Role of Polymer Molecular Conformation.

Poly(lactic- co-glycolic acid) (PLGA) microparticles represent a promising formulation approach for providing steady pharmacokinetic/pharmacodynamic profiles of therapeutic drugs for a long period. Understanding and controlling the supramolecular structure of PLGA microparticles at a molecular level is a prerequisite for the rational design of well-controlled, reproducible sustained-release profiles. Herein, we reveal the role of PLGA molecular conformation in particle formation and drug release. The nanoscale network of PLGA microparticles spray-dried using the solvents with distinct polarities was investigated by using NMR and neutron scattering. By employing chemometric method, we further demonstrate the evolution of nanoscale networks in spray-dried PLGA microparticles upon water absorption. Our results indicate that PLGA molecules form more chain entanglements during spray drying when using the solvents with low polarity, where PLGA molecule adopts a more flexible, extended conformation, resulting in the network being more resistant to water absorption in spray-dried PLGA microparticles. This work underlines the role of PLGA molecular conformation in controlling formation and evolution of nanoscale network of spray-dried PLGA microparticles and will have important consequences in achieving customized drug release from the PLGA microparticles.