Abstract
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.
Highlights
Glioblastoma (GBM) is the most common, aggressive and lethal type of brain cancer, presenting a highly diffuse infiltrative behavior on neighboring structures [1]
Such constitutes the major limitation of the use of hydrogels as anticancer therapy, due to the incompatibility between their hydrophilic matrices and hydrophobic drugs, which generally results in low encapsulation of these same drugs
When tested in human brain tumor MBR 614 cells, it proved to be a successful dual-drug delivery systems (DDS) releasing in a sustained manner both EPI and PTX, stage-by-stage, with the subsequent inhibition of tumor cells growth
Summary
Glioblastoma (GBM) is the most common, aggressive and lethal type of brain cancer, presenting a highly diffuse infiltrative behavior on neighboring structures [1]. If we consider the pharmacological class of antineoplastic agents, we notice that most of them are poorly soluble in aqueous media [13] Such constitutes the major limitation of the use of hydrogels as anticancer therapy, due to the incompatibility between their hydrophilic matrices and hydrophobic drugs, which generally results in low encapsulation of these same drugs. Nanocarrier size, composition and surface characteristics may be modified, awarding them the ability to cross the blood-brain barrier (BBB) following a systemic administration, delivering hydrophilic and/or lipophilic molecules to brain cells They provide a sustained drug release and protect drugs against degradation, significantly increasing their half-life time while reducing toxic effects [17].
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