Brain-targeted, drug-loaded solid lipid nanoparticles against glioblastoma cells in culture

Ak, Güliz; Ünal, Ayşe Zeynep; Özel, Buket; Günel, Nur Selvi; Şanlıer, Şenay Hamarat

doi:10.1016/j.colsurfb.2021.111946

Cited by 28 publications

(13 citation statements)

References 49 publications

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“…Here, certain differences between the size of particles obtained by AFM and DLS are due to the working principles of these characterization methods . It has been reported that the particle size can be reduced by increasing the shear rate, and larger particles are obtained with a low shear rate. ,− Thereby, at first, we used manual shaking (low shear rate) as the emulsification method to prepare JMP to analyze particles via optical microscopy (OM) and to determine whether it is possible to control the geometry by changing the selected variables.…”

Section: Resultsmentioning

confidence: 99%

Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability

Okmen Altas,

Kalaycioglu,

Lifshiz-Simon

et al. 2024

Mol. Pharmaceutics

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Asymmetric geometry (aspect ratio >1), moderate stiffness (i.e., semielasticity), large surface area, and low mucoadhesion of nanoparticles are the main features to reach the brain by penetrating across the nasal mucosa. Herein, a new application has been presented for the use of multifunctional Janus nanoparticles (JNPs) with controllable geometry and size as a noseto-brain (N2B) delivery system by changing proportions of Precirol ATO 5 and polycaprolactone compartments and other operating conditions. To bring to light the N2B application of JNPs, the results are presented in comparison with polymer and solid lipid nanoparticles, which are frequently used in the literature regarding their biopharmaceutical aspects: mucoadhesion and permeability through the nasal mucosa. The morphology and geometry of JPs were observed via cryogenic-temperature transmission electron microscopy images, and their particle sizes were verified by dynamic light scattering, atomic force microscopy, and scanning electron microscopy. Although all NPs showed penetration across the mucus barrier, the best increase in penetration was observed with asymmetric and semielastic JNPs, which have low interaction ability with the mucus layer. This study presents a new and promising field of application for a multifunctional system suitable for N2B delivery, potentially benefiting the treatment of brain tumors and other central nervous system diseases.

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Section: Resultsmentioning

confidence: 99%

Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability

Okmen Altas,

Kalaycioglu,

Lifshiz-Simon

et al. 2024

Mol. Pharmaceutics

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“…Previous studies have indicated that TMZ16e is more stable at an acidic pH than at alkaline and neutral pHs ( Yawen et al, 2021 ). The in vitro release studies of TMZ16e from NPs were performed at pH 5.5 at 37°C, which simulated the tumor micro-environment ( Ak et al, 2021 ). NPs were dialyzed in the dialysis bag (MWCO 14,000 Da) that immersed in phosphate buffered saline (PBS) containing 4% SDS, for 30 days at 37°C on a rocker (100 rpm).…”

Section: Methodsmentioning

confidence: 99%

Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration

Wang

Yu²,

Wang³

et al. 2022

Front. Pharmacol.

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Introduction: Temozolomide (TMZ) is the first-line drug for glioblastoma (GBM), but it is limited in clinical use due to the drug resistance, poor brain targeting, and side effects. Temozolomide hexadecyl ester (TMZ16e), a TMZ derivative with high lipophilicity, membrane permeability, and high anti-glioma properties, has the potential to reverse drug resistance. In this study, anti-ephrin type-A receptor 3 (EphA3) modified TMZ16e loaded nanoparticles (NPs) were prepared for targeted GBM therapy via intranasal administration to deliver TMZ16e to the brain, treat drug-resistant glioma effectively, and reduce peripheral toxicity.Methods: TMZ16e loaded NPs were prepared by emulsion solvent evaporation method followed by modified with anti-EphA3 (anti-EphA3-TMZ16e-NPs). In vitro evaluations were performed by an MTT assay and flow cytometry analysis. The orthotopic nude mice models were used to evaluate the anti-glioma effect in vivo. Additionally, we investigated the anti-drug resistant mechanism by western blot analysis.Results: The particle size of the prepared NPs was less than 200 nm, and the zeta potential of TMZ16e-NPs and anti-EphA3-TMZ16e-NPs were -23.05 ± 1.48 mV and -28.65 ± 1.20mV, respectively, which is suitable for nasal delivery. In vitro studies have shown that anti-EphA3 modification increased the cellular uptake of nanoparticles in T98G cells. The cytotoxicity in the anti-EphA3-TMZ16e-NPs treated group was significantly higher than that of the TMZ16e-NPs, TMZ16e, and TMZ groups (p < 0.01), and the cell cycle was blocked. Western blotting analysis showed that the TMZ16e-loaded NPs were able to effectively downregulate the expression level of O6-methylguanine-deoxyribonucleic acid-methyltransferase (MGMT) protein in T98G cells and reverse drug resistance. In vivo studies showed that the median survival time of tumor-bearing nude mice in the anti-EphA3-TMZ16e-NPs group was extended to 41 days, which was 1.71-fold higher than that of the saline group and the TUNEL staining results of the brain tissue section indicated that the TMZ16e-loaded NPs could elevate apoptosis in T98G cells.Conclusion: In conclusion, the TMZ16e-loaded NPs can be effectively delivered to the brain and targeted to gliomas, exhibiting better anti-glioma activity, indicating they possess great potential in the treatment of drug-resistant glioma.

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“…The TMZ-loaded content in peptides was measured using an HPLC model Agilent 1260 system (Agilent, Santa Clara, CA, USA) equipped with an autosampler and quaternary pump coupled to an Agilent 1260 Infinity Diode Array Detector (DAD) VL (Agilent, Santa Clara, CA, USA) that delivers multiple wavelength detection with full spectra at sampling rates up to 240 Hz. The assay was performed in a Hypersil™ BDS C18 (250 × 4.6 mm × 5 μM) column following a previously defined method [ 52 ]. The mobile phase was composed of the water-methanol mixture (80:20 v / v ) containing 0.5 M acetic acid, which was degassed, and vacuum filtered.…”

Section: Methodsmentioning

confidence: 99%

Development of WRAP5 Peptide Complexes for Targeted Drug/Gene Co-Delivery toward Glioblastoma Therapy

et al. 2022

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Despite the great progress over the past few decades in both the diagnosis and treatment of a great variety of human cancers, glioblastoma remains the most lethal brain tumor. In recent years, cancer gene therapy focused on non-viral vectors which emerged as a promising approach to glioblastoma treatment. Transferrin (Tf) easily penetrates brain cells of the blood–brain barrier, and its receptor is highly expressed in this barrier and glioblastoma cells. Therefore, the development of delivery systems containing Tf appears as a reliable strategy to improve their brain cells targeting ability and cellular uptake. In this work, a cell-penetrating peptide (WRAP5), bearing a Tf-targeting sequence, has been exploited to condense tumor suppressor p53-encoding plasmid DNA (pDNA) for the development of nanocomplexes. To increase the functionality of developed nanocomplexes, the drug Temozolomide (TMZ) was also incorporated into the formulations. The physicochemical properties of peptide/pDNA complexes were revealed to be dependent on the nitrogen to phosphate groups ratio and can be optimized to promote efficient cellular internalization. A confocal microscopy study showed the capacity of developed complexes for efficient glioblastoma cell transfection and consequent pDNA delivery into the nucleus, where efficient gene expression took place, followed by p53 protein production. Of promise, these peptide/pDNA complexes induced a significant decrease in the viability of glioblastoma cells. The set of data reported significantly support further in vitro research to evaluate the therapeutic potential of developed complexes against glioblastoma.

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Brain-targeted, drug-loaded solid lipid nanoparticles against glioblastoma cells in culture

Cited by 28 publications

References 49 publications

Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability

Tadpole-Like Anisotropic Polymer/Lipid Janus Nanoparticles for Nose-to-Brain Drug Delivery: Importance of Geometry, Elasticity on Mucus-Penetration Ability

Temozolomide hexadecyl ester targeted plga nanoparticles for drug-resistant glioblastoma therapy via intranasal administration

Development of WRAP5 Peptide Complexes for Targeted Drug/Gene Co-Delivery toward Glioblastoma Therapy

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