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.
Highlights
The current review provides a brief history of the use of liposome- and chitosan-coated liposome-based formulations in medicine, followed by a focus on their preparation methods and physico-chemical properties, with a particular emphasis on TMZ-liposomal formulations for glioblastoma multiforme (GBM) developed within the last ~10 years
This study provides a systematic investigation on the physico-chemical characterization of liposomes exhibiting promising therapeutic effects, the presented in vivo results are not very conclusive about the effectiveness of CED for liposome delivery when compared to free drug solution
The scope of this work was treatment. None of these studies could reach any of the clinical trial phases, showing to emphasize the challenges and the opportunities associated with this research area aiming a low translational process from bench to bedside
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Extensive literature exists on the topic of brain tumor-targeting drug delivery systems, the interested reader being directed to several insightful reviews [1,13,14,15] All these works highlight the fact that the use of nanocarriers has overcome the common disadvantages of non-encapsulated drugs, while cell uptake was increased and significant extension of survival rate was achieved. There are numerous discussions in the literature on liposome- and chitosan-coated liposome-based formulations in general, encapsulation of TMZ within these transporters is scarcely reported. It appears that this area offers many opportunities for active research. We shall provide both a larger context for the selected carriers, and contributions on TMZ-based formulations whenever literature reports are available
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