Milk-derived exosomes for oral delivery of paclitaxel
01 Jul 2017-Nanomedicine: Nanotechnology, Biology and Medicine (Elsevier)-Vol. 13, Iss: 5, pp 1627-1636
TL;DR: In this article, milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.p. therapy for improved efficacy and reduced toxicity.
About: This article is published in Nanomedicine: Nanotechnology, Biology and Medicine.The article was published on 2017-07-01. It has received 329 citations till now.
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TL;DR: The origin, classification, preparation and characterization, storage stability and applications of exosome delivery system are summarized and discussed by searching a large number of literatures to optimize the above problems and facilitate future functional studies of exOSomes.
Abstract: Exosomes are nano-sized small extracellular vesicles secreted by cells, carrying nucleic acids, proteins, lipids and other bioactive substances to play a role in the body's physiological and pathological processes. Compared to synthetic carriers such as liposomes and nanoparticles, the endogeneity and heterogeneity of exosomes give them extensive and unique advantages in the field of disease diagnosis and treatment. However, the storage stability, low yield, low purity, and weak targeting of exosomes limit its clinical application. For this reason, further exploration is needed to optimize the above problems and facilitate future functional studies of exosomes. In this paper, the origin, classification, preparation and characterization, storage stability and applications of exosome delivery system are summarized and discussed by searching a large number of literatures.
393 citations
TL;DR: A review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell is provided in this paper.
Abstract: Extracellular vesicles (EVs) are the substances that are released by most types of cells and have an important role in cell to cell communication. Among the most highly researched EVs are exosome. Recent studies show that exosomes derived from cells have different roles and targets. Many studies show that exosome can efficiently deliver many different kinds of cargo to the target cell. Therefore, they are often used to deliver therapeutic cargo for treatment. The exosomes that have been used include both natural ones and those that have been modified with other substances to increase the delivery ability. This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.
350 citations
TL;DR: This work investigates publication frequencies on exosomes over the past 10 years, and reviews recent clinical studies on liquid biopsy of exosome in the fields of oncology, pregnancy disorders, cardiovascular diseases, and organ transplantation.
Abstract: Liquid biopsy refers to the sampling and molecular analysis of the biofluids of circulating tumor cells, extracellular vesicles, nucleic acids, and so forth. Exosomes are small extracellular vesicles with sizes between 30–150 nm. They are secreted by multivesicular bodies through exocytosis in live cells and can participate in intercellular communication due to their contents, including nucleic acids, proteins, and lipids. Herein, we investigate publication frequencies on exosomes over the past 10 years, and review recent clinical studies on liquid biopsy of exosomes in the fields of oncology, pregnancy disorders, cardiovascular diseases, and organ transplantation. We also describe the advantages of exosomes as an effective liquid biopsy tool and the progression of exosome extraction methods. Finally, we depict the commercial development of exosome research and discuss the future role of exosomes in liquid biopsy.
326 citations
16 Oct 2018
TL;DR: This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.
Abstract: Extracellular vesicles (EVs) are the substances that are released by most types of cells and have an important role in cell to cell communication. Among the most highly researched EVs are exosome. Recent studies show that exosomes derived from cells have different roles and targets. Many studies show that exosome can efficiently deliver many different kinds of cargo to the target cell. Therefore, they are often used to deliver therapeutic cargo for treatment. The exosomes that have been used include both natural ones and those that have been modified with other substances to increase the delivery ability. This article provides a review of both exosomes derived from various cells and modified exosome and their ability in delivering the many kinds of cargo to the target cell.
269 citations
TL;DR: Current knowledge in the field of EV preservation and storage stability is reported and future directions in the area that could be critical to eventual development of EV therapies are highlighted.
Abstract: Recently, extracellular vesicles (EVs)-including exosomes, microvesicles, and others-have attracted interest as cell-derived biotherapeutics and drug delivery vehicles for a variety of applications. This interest stems from favorable properties of EVs, including their status as mediators of cell-cell communication via transfer of biological cargo and their reported ability to cross biological barriers that impede many delivery systems. However, there are many challenges to translation and widespread application of EV-based therapeutics. One such challenge that has yet to be extensively studied involves EV preservation and storage, which must be addressed to enable use of therapeutic EVs beyond resource-intensive settings. Studies to date suggest that the most promising mode of storage is - 80°C; however, understanding of storage-mediated effects is still limited. Additionally, the effects of storage appear to vary with sample source. The lack of knowledge about and standardization of EV storage may ultimately hinder widespread clinical translation. This mini-review reports current knowledge in the field of EV preservation and storage stability and highlights future directions in the area that could be critical to eventual development of EV therapies.
251 citations
Cites background from "Milk-derived exosomes for oral deli..."
...physical properties, and percent loading of paclitaxel in these EVs also remained stable over this time (14)....
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References
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TL;DR: The improved therapeutic index and elimination of corticosteroid premedication required for solvent-based taxanes make the novel albumin-bound paclitaxel ABI-007 an important advance in the treatment of MBC.
Abstract: Purpose ABI-007, the first biologically interactive albumin-bound paclitaxel in a nanameter particle, free of solvents, was compared with polyethylated castor oil–based standard paclitaxel in patients with metastatic breast cancer (MBC). This phase III study was performed to confirm preclinical studies demonstrating superior efficacy and reduced toxicity of ABI-007 compared with standard paclitaxel. Patients and Methods Patients were randomly assigned to 3-week cycles of either ABI-007 260 mg/m2 intravenously without premedication (n = 229) or standard paclitaxel 175 mg/m2 intravenously with premedication (n = 225). Results ABI-007 demonstrated significantly higher response rates compared with standard paclitaxel (33% v 19%, respectively; P = .001) and significantly longer time to tumor progression (23.0 v 16.9 weeks, respectively; hazard ratio = 0.75; P = .006). The incidence of grade 4 neutropenia was significantly lower for ABI-007 compared with standard paclitaxel (9% v 22%, respectively; P < .001) de...
1,827 citations
"Milk-derived exosomes for oral deli..." refers background in this paper
...FDA in 2005; this formulation has shown enhanced pharmacokinetics [3] and therapeutic efficacy [4]....
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...In a Phase III clinical trial in women with metastatic breast cancer, Abraxane ® -based PAC demonstrated significantly higher response rates and longer time to tumor progression in comparison with CrEL-based PAC [4]....
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TL;DR: With the present development of various new anticancer agents, it is recommended that alternative formulation approaches should be pursued to allow a better control of the toxicity of the treatment and the pharmacological interactions related to the use of CrEL.
1,546 citations
"Milk-derived exosomes for oral deli..." refers background in this paper
...neuropathy which may be associated with demyelination and axonal degeneration [2]....
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Journal Article•
1,385 citations
TL;DR: Oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis.
Abstract: The pH of solid tumors is acidic due to increased fermentative metabolism and poor perfusion. It has been hypothesized that acid pH promotes local invasive growth and metastasis. The hypothesis that acid mediates invasion proposes that H+ diffuses from the proximal tumor microenvironment into adjacent normal tissues where it causes tissue remodeling that permits local invasion. In the current work, tumor invasion and peritumoral pH were monitored over time using intravital microscopy. In every case, the peritumoral pH was acidic and heterogeneous and the regions of highest tumor invasion corresponded to areas of lowest pH. Tumor invasion did not occur into regions with normal or near-normal pHe. Immunohistochemical analyses revealed that cells in the invasive edges expressed the glucose transporter GLUT-1 and the sodium-hydrogen exchanger NHE-1, both of which were associated with peritumoral acidosis. In support of the functional importance of our findings, oral administration of sodium bicarbonate was sufficient to increase peritumoral pH and inhibit tumor growth and local invasion in a preclinical model, supporting the acid-mediated invasion hypothesis.
932 citations
"Milk-derived exosomes for oral deli..." refers background or methods in this paper
...To simulate the slight acidic conditions in the tumor environment [15] in vitro release was performed at pH 6....
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...8 to simulate the slightly acidic conditions of tumour microenvironment [15]....
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TL;DR: A exosome-based system to carry formulation of PTX was developed and showed efficacy in the treatment of multi-drug resistant cancer cells and this novel system may be further developed to carry other chemotherapeutic agents in the future.
877 citations
"Milk-derived exosomes for oral deli..." refers background in this paper
...When this work was completed, a nasal delivery of an exosomal-PAC formulation was reported exhibiting significant efficacy against metastatic lung cancer [11]....
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