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.

Topologically controlled hyaluronan-based gel coatings of hydrophobic grid-like scaffolds to modulate drug delivery.

Scaffolds based on poly(ethyl acrylate) having interwoven channels were coated with a hyaluronan (HA) hydrogel to be used in tissue engineering applications. Controlled typologies of coatings evolving from isolated aggregates to continuous layers, which eventually clog the channels, were obtained by using hyaluronan solutions of different concentrations. The efficiency of the HA loading was determined using gravimetric and thermogravimetric methods, and the hydrogel loss during the subsequent crosslinking process was quantified, seeming to depend on the mass fraction of hyaluronan initially incorporated to the pores. The effect of the topologically different coatings on the scaffolds, in terms of mechanical properties and swelling at equilibrium under different conditions was evaluated and correlated with the hyaluronan mass fraction. The potential of these hydrogel coatings as vehicle for controlled drug release from the scaffolds was validated using a protein model.

New semi-biodegradable materials from semi-interpenetrated networks of poly(ϵ-caprolactone) and poly(ethyl acrylate).

Semi-degradable materials may have many applications. Here poly(ethyl acrylate) and poly(ϵ-caprolactone) were combined as semi-interpenetrated networks, and thoroughly characterized in terms of final composition, interactions between components, wettability, and mechanical properties. PCL modulates the mechanical properties of the PEA elastomeric network. Cultures of fibroblasts and adipose-tissue derived stem cells showed excellent biological performance of the materials. The results are relevant for applications seeking materials leaving a permanent supporting skeleton after the partial degradation, as in patches for cardiac regeneration or in abdominal wall meshes.

Electrospun adherent-antiadherent bilayered membranes based on cross-linked hyaluronic acid for advanced tissue engineering applications.

A procedure to obtain electrospun mats of hyaluronic acid (HA) stable in aqueous media in one single step has been developed. It consists in combining an HA solution with a divinyl sulfone one as cross-linker in a three-way valve to immediately electroblow their mixture. Membranes obtained with this method, after sterilization and conditioning, are ready to use in cell culture without need of any additional post-treatment. HA nanofibers are deposited onto previously electrospun poly(l-lactic acid) (PLLA) mats in order to obtain stably joined bilayered membranes with an adherent face and the opposite face non-adherent, despite their different hydrophilicity and mechanical properties. These bilayered HA/PLLA membranes may be of use, for example, in applications seeking to transplant cells on a tissue surface and keep them protected from the environment: the PLLA nanofiber face is cell friendly and promotes cell attachment and spreading and can thus be used as a cell supply vehicle, while the HA face hinders cell adhesion and thus may prevent post-surgical adherences, a major issue in many surgeries.