scholarly journals Gelatin Methacryloyl Hydrogels Control the Localized Delivery of Albumin-Bound Paclitaxel

Polymers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 501 ◽  
Author(s):  
Margaux Vigata ◽  
Christoph Meinert ◽  
Stephen Pahoff ◽  
Nathalie Bock ◽  
Dietmar W. Hutmacher
Keyword(s):  
Breast Cancer ◽  
Release Kinetics ◽  
Drug Loading ◽  
Cancer Recurrence ◽  
Mesh Size ◽  
Local Delivery ◽  
Breast Cancer Recurrence ◽  
Hydrogel System

Hydrogels are excellent candidates for the sustained local delivery of anticancer drugs, as they possess tunable physicochemical characteristics that enable to control drug release kinetics and potentially tackle the problem of systemic side effects in traditional chemotherapeutic delivery. Yet, current systems often involve complicated manufacturing or covalent bonding processes that are not compatible with regulatory or market reality. Here, we developed a novel gelatin methacryloyl (GelMA)-based drug delivery system (GelMA-DDS) for the sustained local delivery of paclitaxel-based Abraxane®, for the prevention of local breast cancer recurrence following mastectomy. GelMA-DDS readily encapsulated Abraxane® with a maximum of 96% encapsulation efficiency. The mechanical properties of the hydrogel system were not affected by drug loading. Tuning of the physical properties, by varying GelMA concentration, allowed tailoring of GelMA-DDS mesh size, where decreasing the GelMA concentration provided overall more sustained cumulative release (significant differences between 5%, 10%, and 15%) with a maximum of 75% over three months of release, identified to be released by diffusion. Additionally, enzymatic degradation, which more readily mimics the in vivo situation, followed a near zero-order rate, with a total release of the cargo at various rates (2–14 h) depending on GelMA concentration. Finally, the results demonstrated that Abraxane® delivery from the hydrogel system led to a dose-dependent reduction of viability, metabolic activity, and live-cell density of triple-negative breast cancer cells in vitro. The GelMA-DDS provides a novel and simple approach for the sustained local administration of anti-cancer drugs for breast cancer recurrence.

scholarly journals NCAPG confers trastuzumab resistance via activating SRC/STAT3 signaling pathway in HER2-positive breast cancer

2020 ◽  
Vol 11 (7) ◽  
Author(s):  
Lili Jiang ◽  
Liangliang Ren ◽  
Han Chen ◽  
Jinyuan Pan ◽  
Zhuojun Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Recurrence ◽  
Early Recurrence ◽  
Trastuzumab Resistance ◽  
Her2 Positive ◽  
Her2 Breast Cancer ◽  
Structural Maintenance Of Chromosome ◽  
Underlying Mechanisms

AbstractHER2+ breast cancer (BC) is characterized by rapid growth, early recurrence, early metastasis, and chemoresistance. Trastuzumab is the most effective treatment for HER2+ BC and effectively reduces the risk of recurrence and death of patients. Resistance to trastuzumab results in cancer recurrence and metastasis, leading to poor prognosis of HER2+ BC. In the present study, we found that non-structural maintenance of chromosome condensin 1 complex subunit G (NCAPG) expression was highly upregulated in trastuzumab-resistant HER2+ BC. Ectopic NCAPG was positively correlated with tumor relapse and shorter survival in HER2+ BC patients. Moreover, overexpression of NCAPG promoted, while silencing of NCAPG reduced, the proliferative and anti-apoptotic capacity of HER2+ BC cells both in vitro and in vivo, indicating NCAPG reduces the sensitivity of HER2+ BC cells to trastuzumab and may confer trastuzumab resistance. Furthermore, our results suggest that NCAPG triggers a series of biological cascades by phosphorylating SRC and enhancing nuclear localization and activation of STAT3. To summarize, our study explores a crucial role for NCAPG in trastuzumab resistance and its underlying mechanisms in HER2+ BC, and suggests that NCAPG could be both a potential prognostic marker as well as a therapeutic target to effectively overcome trastuzumab resistance.

scholarly journals Electrospun poly (L-lactic acid)/gelatin membranes loaded with doxorubicin for effective suppression of glioblastoma cell growth in vitro and in vivo

2021 ◽  
Author(s):  
Boxun Liu ◽  
Zhizhong Jin ◽  
Haiyan Chen ◽  
Lun Liang ◽  
Yao Li ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Lactic Acid ◽  
Release Kinetics ◽  
Drug Loading ◽  
Composite Membranes ◽  
Spectroscopic Techniques ◽  
Loading Process

Abstract Electrospun membranes are attracting interest as a drug delivery system because of their material composition flexibility and versatile drug loading. In this study, the electrospun membrane was loaded with doxorubicin (DOX) via electrostatic adsorption for long-term drug delivery. DOX loading process was optimized by varying temperature, time, drug concentration, pH, and ionic strength of solutions. The loading process did not impair the structural properties of the membrane. Next, we investigated the drug release kinetics using spectroscopic techniques. The composite membranes released 22% of the adsorbed DOX over the first 48 h, followed by a slower and sustained release over 4 weeks. The DOX release was sensitive to acidic solutions that the release rate at pH 6.0 was 1.27 times as that at pH 7.4. The DOX-loaded membranes were found to be cytotoxic to U-87 MG cells in vitro that decreased the cell viability from 82.92% to 25.49% from 24 h to 72 h of co-incubation. These membranes showed strong efficacy in suppressing tumour growth in vivo in glioblastoma-bearing mice that decreased the tumour volume by 77.33% compared to blank membrane-treated group on Day 20. In conclusion, we have developed an effective approach to load DOX within a clinically-approved poly (L-lactic acid)/gelatin membrane for local and long-term delivery of DOX for the treatment of glioblastoma.

scholarly journals Preparation and Characterization of Paclitaxel Palmitate Albumin Nanoparticles With High Loading Efficacy: an in Vitro and in Vivo Anti-tumor Study in Mouse Models

2020 ◽  
Author(s):  
Hang Chen ◽  
Sifan Huang ◽  
Heyi Wang ◽  
Xinmei Chen ◽  
Haiyan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Drug Loading ◽  
The Body ◽  
Albumin Nanoparticles ◽  
Loading System

Abstract Background: Combination of the prodrug technique with an albumin nanodrug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives. Results: In this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the NabTM technology of paclitaxel palmitate (PTX-PA). Our experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin NPs (Nab-PTX-PA) remained in the tumor for a longer time post injection. Compared with saline and Abraxane® (nanoparticle albumin-bound (nab)-paclitaxel), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organsand more importantly it inhibited tumor cell proliferation more effectively as compared with commercial Abraxane®.Conclusions: This carrier strategy for small molecule drugs is based on naturally evolved interactions between LCFAs(Long Chain Fatty Acids) and HSA(human serum albumin), demonstrated here for PTX. Nab-PTX-PA shows higher maximum tolerated doses and increased efficacy in vivo in breast cancer models, as compared to Abraxane for FDA-approved clinical formulations. This novel injectable Nab-PTX-PA platform has great potential as an effective drug delivery system in the treatment of breast cancer.

Crosslinked Chitosan/PVA Film, Suturated with 5- Fluorouracil for The Prevention of Proliferative Vitreoretinopathy

2016 ◽  
Vol 6 (2) ◽  
Author(s):  
Baiyrkhanova A. ◽  
Ismailova A. ◽  
Botabekova T. ◽  
Enin E. ◽  
Semenova Y.
Keyword(s):  
Proliferative Vitreoretinopathy ◽  
Release Kinetics ◽  
Drug Loading ◽  
In Vitro Release ◽  
Chemical Compositions ◽  
Ophthalmic Administration ◽  
Model Drug ◽  
Kinetics Of

5-Fluorouracil (5-FU)-loaded chitosan (Ch) film for chemotherapy were prepared applying a superhydrophobic surfacebased encapsulation technology. The aim of this study was to develop polymeric film with glutaraldehyde (GA) of controlled drug delivery systems for 5 – fluorouracil (FU) as a model drug for the treatment of proliferative vitreoretinopathy. Polymer film of chitosan and polyvinyl alcohol (PVA in 75:25 ratios were prepared and treated with GA. FTIR spectra of 5-FU, Ch/5-FU and Ch/PVA film loaded 5-FU were studied. Physical characteristics such as thickness and swelling coefficient of the film were performed. The thermal of the Ch/PVA film was studied with thermogravimethric analysis. The drug loading efficiency, film size and chemical compositions of the film loaded drug were confirmed by UV–vis spectrophotometer and Fourier transform infrared spectroscopy. In vitro release kinetics of drug from the polymeric films was investigated to determine the drug release properties. In vivo study of PVR was showed the efficacy and no toxicity of this formulation. Further uses of the film loaded 5 - fluorouracil may provide an efficiency deliverable for ophthalmic administration.

scholarly journals Potential miRNAs for miRNA-Based Therapeutics in Breast Cancer

2020 ◽  
Vol 6 (3) ◽  
pp. 29
Author(s):  
Jun Sheng Wong ◽  
Yoke Kqueen Cheah
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Cancer Recurrence ◽  
Mirna Biogenesis ◽  
In Vivo Models ◽  
Cellular Processes ◽  
Non Coding Rnas ◽  
Tumor Suppressor Mirnas

MicroRNAs (miRNAs) are small non-coding RNAs that can post-transcriptionally regulate the genes involved in critical cellular processes. The aberrant expressions of oncogenic or tumor suppressor miRNAs have been associated with cancer progression and malignancies. This resulted in the dysregulation of signaling pathways involved in cell proliferation, apoptosis and survival, metastasis, cancer recurrence and chemoresistance. In this review, we will first (i) provide an overview of the miRNA biogenesis pathways, and in vitro and in vivo models for research, (ii) summarize the most recent findings on the roles of microRNAs (miRNAs) that could potentially be used for miRNA-based therapy in the treatment of breast cancer and (iii) discuss the various therapeutic applications.

scholarly journals Resveratrol-Loaded TPGS-Resveratrol-Solid Lipid Nanoparticles for Multidrug-Resistant Therapy of Breast Cancer: In Vivo and In Vitro Study

2021 ◽  
Vol 9 ◽  
Author(s):  
Wenrui Wang ◽  
Mengyang Zhou ◽  
Yang Xu ◽  
Wei Peng ◽  
Shiwen Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Therapy ◽  
Solid Lipid Nanoparticles ◽  
Drug Loading ◽  
Lipid Nanoparticles ◽  
Significant Inhibition ◽  
Migration And Invasion ◽  
Solid Lipid

Multidrug resistance (MDR) is a serious problem during cancer therapy. The purpose of the present study was to formulate D-α-Tocopheryl polyethylene glycol 1000 succinate-resveratrol-solid lipid nanoparticles (TPGS-Res-SLNs) to improve its therapeutic efficacy against breast cancer. In this study, the solvent injection method was used to prepare the TPGS-Res-SLNs. It was found that the TPGS-Res-SLNs exhibited zeta potential and drug-loading of −25.6 ± 1.3 mV and 32.4 ± 2.6%, respectively. Therefore, it was evident that the TPGS-Res-SLNs can increase cellular uptake of chemotherapeutic drugs, induce mitochondrial dysfunction, and augment tumor treatment efficiency by inducing apoptosis. Moreover, it was found that SKBR3/PR cells treated with TPGS-Res-SLNs exhibited significant inhibition of cell migration and invasion, as compared with free resveratrol. In addition, results from in vivo SKBR3/PR xenograft tumor models revealed that TPGS-Res-SLNs has better efficacy in promoting apoptosis of tumor cells owing to high therapeutic outcomes on tumors when compared with the efficacy of free resveratrol. In conclusion, the findings of the present study indicate significant potential for use of TPGS-Res-SLNs as an efficient drug delivery vehicle to overcome drug resistance in breast cancer therapy.

RESEALED ERYTHROCYTES: A PROMISING APPROACH TO ENHANCE EFFICACY OF ANTICANCER DRUGS

INDIAN DRUGS ◽  
2020 ◽  
Vol 57 (03) ◽  
pp. 9-20
Author(s):  
◽  
Prathibha Salve ◽  
Rajendra Doijad ◽  
Niranjan Chivate
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Anticancer Drugs ◽  
Delivery System ◽  
Release Kinetics ◽  
Drug Loading ◽  
The Body ◽  
Zero Order Release

Targeted drug delivery system is a potential drug delivery system which delivers the drug to particular organ of interest only. This improves the therapeutic efficacy of the treatment by reducing the side effects of drug which are required in case of anticancer drugs. Erythrocytes have been the most interesting carrier and have found to possess great potential in drug targeting. Resealed erythrocytes are gaining more popularity because of their ability to circulate throughout the body, biocompatibility, zero order release kinetics, reproducibility and ease of preparation. In this review, we have made an attempt to understand the process in detail to prepare resealed erythrocytes, including its mechanism, source and isolation of erythrocytes, methods of drug loading, in vivo and in vitro characterization of resealed erythrocytes, with special emphasis on applications of resealed erythrocytes for cancer treatment. With this review we can conclude that resealed erythrocyte is a promising approach to enhance efficacy of anticancer drugs.

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