Mehdi Esfandyari-Manesh

Glioblastoma (GBM), a grade IV astrocytoma, is defined by its rapid proliferation, strong infiltrative nature, resistance to chemotherapy, and tendency to recur quickly, even after surgery and standard treatments. We hypothesize that the localized delivery of ibrutinib loaded in PLGA-PEG-folate nanoparticles (IBT-PPF-NPs) and Octreotide PLGA microparticles (OCT-PLGA-MPs) loaded GelMA hydrogel into GBM tumors represents a promising approach, as it can achieve a high local drug concentration in the tumor site and increase the efficacy of treatment. The OCT-PLGA-MPs were prepared and incorporated with IBT-PPF-NPs in GelMA-alginate hydrogel. The in-situ hydrogel was developed using GelMA combined with different alginate concentrations, and its swelling behavior, degradation rate, and mechanical and morphological characteristics were investigated. The efficiency of Octreotide entrapment in PLGA microparticle was 55.0% ± 0.7 with 5.0% ± 0.03 drug loading. The particle size of the OCT-PLGA-MPs was 103 μm ± 5.6. Octreotide exhibited a gradual release profile from the microparticles (MPs), with approximately 5.2% released within the first 24 h and up to 71% released over 84 days. The embedding of OCT-PLGA-MPs within the hydrogel and IBT-PPF-NPs effectively controls the initial burst release typically observed with NPs and MPs. The structure of the GelMA was verified through 1H NMR analysis. The selected hydrogel demonstrated an elastic modulus of 18.45 kPa, consistent with the mechanical properties of brain tissue. MTT assay results revealed that IBT-PPF-NPs inhibit the growth of glioma cells in a dose-dependent manner, while Octreotide alone exhibited no cytotoxic effect on glioma cells. The MTT results also indicate an additive effect between the combination of the two treatments. An in vivo study was performed to evaluate the effectiveness of intratumoral injection of hydrogel in inhibiting tumor growth by MRI imaging. Then the collected brain tumors were evaluated by H&E and IHC staining analysis. The hydrogel containing IBT-PPF-NPs and OCT-PLGA-MPs effectively suppressed tumor growth in the in vivo study. The IHC results revealed a significant increase in caspase-3 levels and a decrease in the Ki-67 marker in glioma tumor cells by ibrutinib. On the other hand, Octreotide notably reduced CD31 expression, inhibiting angiogenesis and effectively suppressing both tumor growth and glioma cell proliferation in the in vivo study. It holds potential as a valuable approach for post-resection management of GBM, preceding standard chemo-radiation therapy.

Glioblastoma (GBM), a grade IV astrocytoma, is defined by its rapid proliferation, strong infiltrative nature, resistance to chemotherapy, and tendency to recur quickly, even after surgery and standard treatments. We hypothesize that the localized delivery of ibrutinib loaded in PLGA-PEG-folate nanoparticles (IBT-PPF-NPs) and Octreotide PLGA microparticles (OCT-PLGA-MPs) loaded GelMA hydrogel into GBM tumors represents a promising approach, as it can achieve a high local drug concentration in the tumor site and increase the efficacy of treatment. The OCT-PLGA-MPs were prepared and incorporated with IBT-PPF-NPs in GelMA-alginate hydrogel. The in-situ hydrogel was developed using GelMA combined with different alginate concentrations, and its swelling behavior, degradation rate, and mechanical and morphological characteristics were investigated. The efficiency of Octreotide entrapment in PLGA microparticle was 55.0% ± 0.7 with 5.0% ± 0.03 drug loading. The particle size of the OCT-PLGA-MPs was 103 µm ± 5.6. Octreotide exhibited a gradual release profile from the microparticles (MPs), with approximately 5.2% released within the first 24 hours and up to 71% released over 84 days. The embedding of OCT-PLGA-MPs within the hydrogel and IBT-PPF-NPs effectively controls the initial burst release typically observed with NPs and MPs. The structure of the GelMA was verified through H NMR analysis. The selected hydrogel demonstrated an elastic modulus of 18.45 kPa, consistent with the mechanical properties of brain tissue. MTT assay results revealed that IBT-PPF-NPs inhibit the growth of glioma cells in a dose-dependent manner, while Octreotide alone exhibited no cytotoxic effect on glioma cells. The MTT results also indicate an additive effect between the combination of the two treatments. An in vivo study was performed to evaluate the effectiveness of intratumoral injection of hydrogel in inhibiting tumor growth by MRI imaging. Then the collected brain tumors were evaluated by H&E and IHC staining analysis. The hydrogel containing IBT-PPF-NPs and OCT-PLGA-MPs effectively suppressed tumor growth in the in vivo study. The IHC results revealed a significant increase in caspase-3 levels and a decrease in the Ki-67 marker in glioma tumor cells by ibrutinib. On the other hand, Octreotide notably reduced CD31 expression, inhibiting angiogenesis and effectively suppressing both tumor growth and glioma cell proliferation in the in vivo study. It holds potential as a valuable approach for post-resection management of GBM, preceding standard chemo-radiation therapy.

The global incidence of melanoma, the most lethal form of skin cancer, continues to escalate, emphasizing the urgent need for more effective therapeutic strategies. This review assesses the latest advancements in topical and transdermal drug delivery systems, positioning them as promising alternatives. These systems allow for the direct application of therapeutic agents to tumor sites, enhancing drug effectiveness, improving patient compliance, and reducing systemic toxicity. Specifically, innovations such as nanoparticles, microneedles, and vesicular systems are explored for their potential to optimize topical and localized drug delivery. By incorporating a graphical overview of these drug delivery vehicles, we visually underscore their roles in enhancing therapeutic outcomes across various treatment categories such as chemotherapy, immunotherapy, phototherapy, phytotherapy, and targeted therapy. This article critically evaluates recent breakthroughs, addresses the current challenges faced by researchers, and explores the future directions of topical and transdermal approaches in melanoma management. By presenting a summary of the latest research and predicting future trends, this review aims to inform ongoing developments and encourage further innovation in strategies for treating melanoma. Graphical abstract Illustration of the drug delivery carriers used for the melanoma topical and transdermal treatment approaches since 2016

Paclitaxel (PTX), an antimitotic drug from the taxanes group, prevents the proliferation of breast cancer cells through mitosis arrest and activation by a cascade of signaling pathways that lead to apoptosis. Mitochondria is one of the important signaling routes for inducing apoptosis. For mitochondria targeting, triphenylphosphonium (TPP) with a delocalized charge and hydrophobic nature was utilized as a moiety to facilitate penetration through a phospholipid membrane of mitochondria. PTX-TPP was synthesized via pH-sensitive ester bond between hydroxyl groups of PTX and carboxylic acid of (4-carboxybutyl) TPP. Then PTX-TPP prodrug encapsulated in alginate nanoparticles, which were self-assembled by the ionotropic complexation technique for enhancement of mitochondrial apoptosis in breast cancer cells. The loading of PTX-TPP conjugation in self-assembled alginate nanoparticles was 16.5% and the particle size of nanoparticles was 123 nm with zeta potential around − 25.8 Mv. The in vitro cytotoxicity and IC50 of PTX-TPP nanoparticles in the growth of MCF7 cancer cell increased 6.3-fold higher than free PTX. The early apoptotic cells and the late apoptotic/necrotic cells for PTX-TPP nanoparticles were 11.6 and 3.9-fold higher than free PTX. This study indicated this mitochondrial-targeted self-assembled nanoparticles can inhibit the tumor cell growth of breast cancer.

One of the most common types of bone cancer is osteosarcoma. Currently a combination of therapies including surgery, chemotherapy, and radiation therapy is used. Bone defects, re-formation of the tumor, or remaining tumor cells after the surgery are the main challenges of osteosarcoma treatments. Scaffolds can be used to overcome the bone defects problem. In this study, we aim to fabricate a bilayer scaffold with the capacity of avoiding tumor recurrence and stimulating bone regeneration which brings a novel idea for osteosarcoma treatments. First, methotrexate was encapsulated in PLGA microspheres with 13.5% loading capacity. Then, coaxial extrusion-based 3D printer via a customized bilayer core-shell nozzle was employed to fabricate the scaffold. The implanted scaffold was printed by using gelatin methacrylol (GelMA) hydrogel containing methotrexate microspheres in the outer layer for anticancer drug delivery, and GelMA/alginate hydrogel containing nanohydroxyapatite and nanosilica in the inner layer for bone regeneration. The outer layer of the scaffold had rapidly degraded within 20 days and it played a great role in drug delivery and inhibiting the tumor cells’ growth. The inner layer with 4% nanosilica had slow degradation rate at about 50% in 60 days and it showed the highest mechanical strength with 225 kPa. Regarding osteogenesis property, ALP enzyme activity was increased considerably within 3 weeks. Also, significant increase in osteogenesis markers of RUNX2, OPN, and COL1A1 was observed. In addition to drug delivery at the tumor site, this bilayer scaffold could be a platform for the placement of healthy bone cells after drug delivery.