L-Dopa release from mesoporous silica nanoparticles engineered through the concept of drug-structure-directing agents for Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease, the 2nd most common after Alzheimer's disease, the main effect of which is the loss of dopaminergic neurons. Levodopa or l-Dopa is an amino acid used in the treatment of PD that acts as the immediate precursor to dopamine. However, over time the efficacy of the medication gradually decreases requiring modified delivery methods. One of the major challenges for the medication to work is to achieve a gradual continuous supply of l-Dopa to the brain to minimise symptoms. Herein, mesoporous silica nanoparticles (MSNs) were engineered through the concept of drug-structure-directing agents (DSDAs) with inherent therapeutic activity. The DSDA used was l-Dopa drug modified by amidation with fatty acids to build anionic surfactants that were able to form micelles as templates for the assembly of inorganic precursors to form the silica framework. This templating route produced MSNs with tunable sizes ranging from 100 nm to 1 µm and with different shapes: spherical, with either solid structures with radial mesopores and porous shells, or hollow-shells with inside large void cavities; and elongated, characterized by long hollows covered by mesoporous shells. The concept of using DSDAs to synthesize drug nanocarriers can be used to avoid the surfactant removal and subsequent drug loading steps involved in the synthesis of conventional MSNs. We hypothesized that the l-Dopa released from MSN materials is mediated by the size and solubility of the DSDAs, and the surface chemical interactions between the DSDAs and MSN hosts. Different pHs (acidic and neutral) simulating gastrointestinal tract conditions were tested, and the results showed hardly any release for gastric conditions at pH 1.2, avoiding the premature release in the stomach typical of conventional MSNs, while for intestinal conditions of pH 7.4, the release of l-Dopa occurred in a continuous and sustained manner, which is well suited to the drug's application and delivery route, and matches well with achieving a sustained l-Dopa delivery to relief symptoms. This could open up new uses for MSNs synthesized by this approach to treat PD.

Influence of the structural and textural properties of ordered mesoporous materials and hierarchical zeolitic supports on the controlled release of methylprednisolone hemisuccinate.

To alleviate the chronic inflammation, nasal obstruction, and loss of sense of smell that produces the rhinosinusitis disease, ordered mesoporous materials and hierarchical zeolites could be used for slow and sustained corticoid (methylprednisolone hemisuccinate conjugate) release. The correlations between the delivery performance of methylprednisolone hemisuccinate and the physicochemical properties of carriers' release systems, including pore mesostructure, texture and size, and surface chemistry, have been well established. Different two-dimensional (2-D) and three-dimensional (3-D) mesostructured materials (MCM-41, SBA-15, expanded SBA-15, FDU-12, and SBA-16) were employed. In addition, for the first time to the best of our knowledge, materials based on hierarchical zeolites with additional mesoporosity (h-ZSM-5 and h-BETA zeolites) were also tested. In particular, two materials (3-D cubic mesoporous silica SBA-16 and hierarchical Beta zeolite) have been probed to be potential candidates, exhibiting high drug adsorption capacities and slow drug release rates, which is the most favourable way of drug release in the particular rhinosinusitis application. Solid-state 1H-29Si HETCOR NMR analyses confirm the strong interactions of the drug with the surface of h-BETA and 3-D SBA-16 materials, via hydrogen bonding of carboxylic, ketone, and aliphatic moieties of the methylprednisolone hemisuccinate at surface silanol sites. Because of the remarkable release performance, it is expected that 3-D mesoporous silica SBA-16 and hierarchical Beta zeolite can be attractive candidates for current applications in nasal inflammation treatments. The drug release rate can be further retarded by decreasing the pH to around 4.6; at this point more attraction forces were detected as proved by zeta-potential measurements. Therefore, a slower delivery trend of methylprednisolone hemisuccinate has been observed for all the materials, which is more pronounced in the case of SBA-15 and SBA-16.