Nanocarriers for the delivery of temozolomide in the treatment of glioblastoma

Ramalho, Maria João; Coelho, Manuel A. N.; Pereira, Maria do Carmo

doi:10.1016/b978-0-12-813627-0.00018-1

Cited by 18 publications

(13 citation statements)

References 117 publications

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“…The complexation of TMZ to other macromolecules and nanoparticles has also been reported to enhance drug stability, with decomposition kinetics slower than that of free TMZ [1,77,78]. This result could explain the different decomposition half-lives reported in the literature, for TMZ at 37 • C in buffer (1 h) and blood plasma (1.8 h) [3,6]. The enhancement observed in plasma may be due to the interaction of TMZ with the plasma proteins, as demonstrated here, and with other components which protect the drug from the external environment.…”

Section: Stability Of Tmz-hsa Complexmentioning

confidence: 99%

“…Current treatment options are multimodal and include surgical resection, radiation and chemotherapy [1]. The prodrug temozolomide (TMZ), a bis(imidazotetrazine) heterocycle, is the main chemotherapeutic agent used [2][3][4]. Combined with radiation therapy, it contributes to extend the survival period and improves the patient's quality of life [5].…”

Section: Introductionmentioning

confidence: 99%

“…This highly reactive cation interacts with the DNA, causing its methylation, and this consequently results in cell death [7]. TMZ requires continuous administration due to its low solubility and specificity, as well as short half-life in blood plasma (≈1.8 h) [3,6]. As a result of prolonged therapy, the drug causes important side effects which results in many cases in the need to interrupt the treatment.…”

Section: Introductionmentioning

confidence: 99%

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The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

et al. 2020

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The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing π-stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.

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Section: Stability Of Tmz-hsa Complexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

et al. 2020

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“…The first-line treatment of glioma tumors is based on a multimodal approach combining tumor resection with surgery, chemotherapy and radiotherapy. However, its high proliferation rate and invasiveness contributes to its high resistance to therapy ( Bush et al, 2017 ; Ramalho et al, 2018a ). Inhibition of carcinogenesis by RES in glioma tumors can occur at several stages, as inhibition of angiogenesis, induction of apoptosis, tumor growth inhibition, and cell cycle regulation.…”

Section: Glioma Tumorsmentioning

confidence: 99%

Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment

et al. 2018

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Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer’s (AD) and Parkinson’s (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death. In brain cancer, RES induces cell apoptotic death and inhibits angiogenesis and tumor invasion. Despite its great potential as therapeutic agent for the treatment of several diseases, RES exhibits some limitations. It has poor water solubility and it is chemically instable, being degraded by isomerization once exposed to high temperatures, pH changes, UV light, or certain types of enzymes. Thus, RES has low bioavailability, limiting its biological and pharmacological benefits. To overcome these limitations, RES can be delivered by nanocarriers. This field of nanomedicine studies how the drug administration, pharmacokinetics, and pharmacodynamics are affected by the use of nanosized materials. The role of nanotechnology, in the prevention and treatment of neurological diseases, arises from the necessity to mask the physicochemical properties of therapeutic drugs to prolong the half-life and to be able to cross the blood–brain barrier (BBB). This can be achieved by encapsulating the drug in a nanoparticle (NP), which can be made of different kinds of materials. An increasing trend to encapsulate and direct RES to the brain has been observed. RES has been encapsulated in many different types of nanosystems, as liposomes, lipid and polymeric NPs. Furthermore, some of these nanocarriers have been modified with targeting molecules able to recognize the brain areas. Then, this article aims to overview the RES benefits and limitations in the treatment of neurological diseases, as the different nanotechnology strategies to overcome these limitations.

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“…Surgical resection, followed by radiation with simultaneous chemotherapy, as part of a combined modality approach, is among the most frequent current treatments. Yet, although recent advances in handling many solid tumors, the treatment of GBM remains weak with a median survival of [12][13][14][15] Pharmaceutics 2021, 13, 378 2 of 12 months [4]. Treatment limits derive from radiotherapy and chemotherapy resistance, side effects limiting treatments and, mostly, low drug concentration in the brain [5,6].…”

Section: Introductionmentioning

confidence: 99%

Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide

et al. 2021

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Nanoparticles (NPs) have emerged as an effective means to deliver anticancer drugs into the brain. Among various forms of NPs, liposomal temozolomide (TMZ) is the drug-of-choice for the treatment and management of brain tumours, but its therapeutic benefit is suboptimal. Although many possible reasons may account for the compromised therapeutic efficacy, the inefficient tumour penetration of liposomal TMZ can be a vital obstacle. Recently, the protein corona, i.e., the layer of plasma proteins that surround NPs after exposure to human plasma, has emerged as an endogenous trigger that mostly controls their anticancer efficacy. Exposition of particular biomolecules from the corona referred to as protein corona fingerprints (PCFs) may facilitate interactions with specific receptors of target cells, thus, promoting efficient internalization. In this work, we have synthesized a set of four TMZ-encapsulating nanomedicines made of four cationic liposome (CL) formulations with systematic changes in lipid composition and physical−chemical properties. We have demonstrated that precoating liposomal TMZ with a protein corona made of human plasma proteins can increase drug penetration in a 3D brain cancer model derived from U87 human glioblastoma multiforme cell line leading to marked inhibition of tumour growth. On the other side, by fine-tuning corona composition we have also provided experimental evidence of a non-unique effect of the corona on the tumour growth for all the complexes investigated, thus, clarifying that certain PCFs (i.e., APO-B and APO-E) enable favoured interactions with specific receptors of brain cancer cells. Reported results open new perspectives into the development of corona-coated liposomal drugs with enhanced tumour penetration and antitumour efficacy.

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Nanocarriers for the delivery of temozolomide in the treatment of glioblastoma

Cited by 18 publications

References 117 publications

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug

Resveratrol Brain Delivery for Neurological Disorders Prevention and Treatment

Inhibiting the Growth of 3D Brain Cancer Models with Bio-Coronated Liposomal Temozolomide

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