Abstract
Background: High-grade gliomas (HGGs) are highly malignant tumors with a poor survival rate. The inability of free drugs to cross the blood–brain barrier and their off-target accumulation result in dose-limiting side effects. This study aimed at enhancing the encapsulation efficiency (EE) of irinotecan hydrochloride trihydrate (IRH) within polycaprolactone (PCL) nanoparticles with optimized size and charge. Materials and Methods: IRH-loaded PCL nanoparticles were formulated using either the single emulsion (O/W, W/O and O/O) or double emulsion (W/O/O and W/O/W) solvent evaporation techniques. The nanoparticles were characterized for their size, zeta potential and EE, with the optimized nanoparticles being characterized for their drug release and cytotoxicity. Results: The amorphization of PCL and the addition of electrolytes to the aqueous phases of the W/O/W emulsion produced spherical nanoparticles with a mean diameter of 202.1 ± 2.0 nm and an EE of 65.0%. The IRH-loaded nanoparticles exhibited zero-order release and were cytotoxic against primary HGG cells. Conclusion: The amorphization of PCL improves its EE of hydrophilic drugs, while the addition of electrolytes to the aqueous phases of the W/O/W emulsion enhances their EE further. IRH-loaded PCL nanoparticles have the potential to deliver cytotoxic levels of IRH over a sustained period of time, enhancing the cell death of HGGs.
Highlights
Malignant brain tumors are associated with high mortality and morbidity rates, owing to the lack of long-term disease control
Several hurdles limit the efficacy of glioma treatment: (1) glioma cells can metastasize to other tissues in the brain and their irregular margins make complete resection difficult; (2) the blood–brain barrier (BBB) prevents drug molecules from entering the brain at therapeutic concentrations [4]; (3) cancer stem cells contribute to tumor initiation and therapeutic resistance and (4) glioma cells are immortalized in nature and any cells left behind during surgery will develop into a new tumor [5]
In PBS, irinotecan hydrochloride trihydrate (IRH) loses more than 70% of its stability within 24 h, which remains constant over 16 days, with temperature having no effect (Figure 1C)
Summary
Malignant brain tumors are associated with high mortality and morbidity rates, owing to the lack of long-term disease control. The majority of malignant brain tumors that affect adults are gliomas, with high-grade gliomas (HGGs) accounting for 75% [1]. 100,000 population, 3 to 5 persons develop gliomas annually, with a higher frequency in men. The fifth and sixth decades of life are the most prominent for glioma incidence, gliomas can develop at any age [2]. In 2016, the WHO included genetic criteria in classifying gliomas, which resulted in identifying anaplastic astrocytoma, anaplastic oligodendroglioma and mixed anaplastic oligoastrocytoma (grade III) and glioblastoma (grade IV) as high-grade gliomas, accounting for the majority of cases, with a 60 to 70%. Several hurdles limit the efficacy of glioma treatment: (1) glioma cells can metastasize to other tissues in the brain and their irregular margins make complete resection difficult; (2) the blood–brain barrier (BBB) prevents drug molecules from entering the brain at therapeutic concentrations [4]; (3) cancer stem cells contribute to tumor initiation and therapeutic resistance and (4) glioma cells are immortalized in nature and any cells left behind during surgery will develop into a new tumor [5]
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