ABSTRACT
Layered double hydroxides (LDHs) or hydrotalcite-like compounds have attracted great attention for the delivery of anticancer drugs due to their 2D structure, exhibiting a high surface-to-volume ratio and a high chemical versatility. The drug is protected between the layers from which it is slowly released, thus increasing the therapeutic effect and minimizing the side effects associated to nonspecific targeting. This work aimed to design LDHs with Mg and Al (molar ratio of 2/1) in brucite-like layers, which retained fluorouracil (5-FU; 5-FU/Al = 1, molar ratio) in the interlayer gallery as the layers grow during the co-precipitation step of the synthesis. To rationally control the physicochemical properties, particularly the size of the crystallites, the aging step following the co-precipitation was performed under carefully controlled conditions by changing the time and temperature (i.e., 25 °C for 16 h, 100 °C for 16 h, and 120 °C for 24 h). The results revealed the achievement of the control of the size of the crystals, which are gathered in three different agglomeration systems, from tight to loose, as well as the loading degree of the drug in the final organic-inorganic hybrid nanomaterials. The role played by the factors and parameters affecting the drug-controlled release was highlighted by assessing the release behavior of 5-FU by changing the pH, solid mass/volume ratio, and ionic strength. The results showed a pH-dependent behavior but not necessarily in a direct proportionality. After a certain limit, the mass of the solid diminishes the rate of release, whereas the ionic strength is essential for the payload discharge.
ABSTRACT
Glioblastoma (GBM) is a lethal brain cancer with a very difficult therapeutic approach and ultimately frustrating results. Currently, therapeutic success is mainly limited by the high degree of genetic and phenotypic heterogeneity, the blood brain barrier (BBB), as well as increased drug resistance. Temozolomide (TMZ), a monofunctional alkylating agent, is the first line chemotherapeutic drug for GBM treatment. Yet, the therapeutic efficacy of TMZ suffers from its inability to cross the BBB and very short half-life (~2 h), which requires high doses of this drug for a proper therapeutic effect. Encapsulation in a (nano)carrier is a promising strategy to effectively improve the therapeutic effect of TMZ against GBM. Although research on liposomes as carriers for therapeutic agents is still at an early stage, their integration in GBM treatment has a great potential to advance understanding and treating this disease. In this review, we provide a critical discussion on the preparation methods and physico-chemical properties of liposomes, with a particular emphasis on TMZ-liposomal formulations targeting GBM developed within the last decade. Furthermore, an overview on liposome-based formulations applied to translational oncology and clinical trials formulations in GBM treatment is provided. We emphasize that despite many years of intense research, more careful investigations are still needed to solve the main issues related to the manufacture of reproducible liposomal TMZ formulations for guaranteed translation to the market.
