Chemotherapy is commonly associated with limited effectiveness and unwanted side effects in normal cells and tissues, due to the lack of specificity of therapeutic agents to cancer cells when systemically administered. In brain tumors, the existence of both physiological barriers that protect tumor cells and complex resistance mechanisms to anticancer drugs are additional obstacles that hamper a successful course of chemotherapy, thus resulting in high treatment failure rates. Several potential surrogate therapies have been developed so far. In this context, hydrogel-based systems incorporating nanostructured drug delivery systems (DDS) and hydrogel nanoparticles, also denoted nanogels, have arisen as a more effective and safer strategy than conventional chemotherapeutic regimens. The former, as a local delivery approach, have the ability to confine the release of anticancer drugs near tumor cells over a long period of time, without compromising healthy cells and tissues. Yet, the latter may be systemically administered and provide both loading and targeting properties in their own framework, thus identifying and efficiently killing tumor cells. Overall, this review focuses on the application of hydrogel matrices containing nanostructured DDS and hydrogel nanoparticles as potential and promising strategies for the treatment and diagnosis of glioblastoma and other types of brain cancer. Some aspects pertaining to computational studies are finally addressed.

A properly designed nanosystem aims to deliver an optimized concentration of the active pharmaceutical ingredient (API) at the site of action, resulting in a therapeutic response with reduced adverse effects. Due to the vast availability of lipids and surfactants, producing stable lipid dispersions is a double-edged sword: on the one hand, the versatility of composition allows for a refined design and tuning of properties; on the other hand, the complexity of the materials and their physical interactions often result in laborious and time-consuming pre-formulation studies. However, how can they be tailored, and which premises are required for a “right at first time” development? Here, a stepwise framework encompassing the sequential stages of nanoparticle production for disulfiram delivery is presented. Drug in lipid solubility analysis leads to the selection of the most suitable liquid lipids. As for the solid lipid, drug partitioning studies point out the lipids with increased capacity for solubilizing and entrapping disulfiram. The microscopical evaluation of the physical compatibility between liquid and solid lipids further indicates the most promising core compositions. The impact of the outer surfactant layer on the colloidal properties of the nanosystems is evaluated recurring to machine learning algorithms, in particular, hierarchical clustering, principal component analysis, and partial least squares regression. Overall, this work represents a comprehensive systematic approach to nanoparticle formulation studies that serves as a basis for selecting the most suitable excipients that comprise solid lipid nanoparticles and nanostructured lipid carriers.

The current study describes the application of an Analytical Quality by Design (AQbD) approach for the selection and optimization of a reversed-phase high performance liquid chromatography (RP-HPLC) method to simultaneously quantify curcumin, atorvastatin calcium and celecoxib in lipid nanoparticles. Risk assessment was carried out to set the risk factors that may have a significant influence on method performance. Mobile phase composition and flow rate were identified as critical method parameters, and a 3^k full factorial design with center point was applied to understand their impact on the number of theoretical plates, retention time, peak resolution, tailing factor and sensitivity. Statistical modeling, followed by response surface analysis led to the characterization of the method operable design region (MODR) and the selection of the most suitable chromatographic conditions for validation, following Food and Drug Administration and International Council on Harmonisation recommendations. The mobile phase was composed of 2% v/v glacial acetic acid : acetonitrile (50 : 50, v/v) and was eluted at an isocratic flow rate of 1.0 mL min⁻¹. The analyses were performed on a Kinetex® EVO C18 column (Torrance, USA), with 5 μm particle size, 4.6 μm internal diameter and 150 mm length, at 35 °C and under UV-vis detection at 425 (curcumin), 247 (atorvastatin calcium) and 250 nm (celecoxib). Retention time values of curcumin, atorvastatin calcium and celecoxib were found to be 4.520, 5.033 and 7.576 min, respectively. AQbD provided a comprehensive framework for developing a reliable, effective, flexible band robust method for the routine analysis of the compounds in quality control laboratories.