Recent advances in lymphatic targeted drug delivery system for tumor metastasis
01 Jan 2014-Iss: 4, pp 247-254
TL;DR: Novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes and recent advances in the development of lymphatics targeted carriers are discussed.
Abstract: The lymphatic system has an important defensive role in the human body. The metastasis of most tumors initially spreads through the surrounding lymphatic tissue and eventually forms lymphatic metastatic tumors; the tumor cells may even transfer to other organs to form other types of tumors. Clinically, lymphatic metastatic tumors develop rapidly. Given the limitations of surgical resection and the low effectiveness of radiotherapy and chemotherapy, the treatment of lymphatic metastatic tumors remains a great challenge. Lymph node metastasis may lead to the further spread of tumors and may be predictive of the endpoint event. Under these circumstances, novel and effective lymphatic targeted drug delivery systems have been explored to improve the specificity of anticancer drugs to tumor cells in lymph nodes. In this review, we summarize the principles of lymphatic targeted drug delivery and discuss recent advances in the development of lymphatic targeted carriers.
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TL;DR: This review encompasses novel strategies for more effective chemotherapeutic delivery aiming to generate better prognosis in cancer and significant advances are being made in the development of novel cancer treatment strategies.
128 citations
Cites background from "Recent advances in lymphatic target..."
...Ligands are designed to generate high binding affinity to plasma membrane of cancer cells [31-33]....
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TL;DR: The critical importance of potency in achieving the LA outcome for injectable formulations is focused upon and the gaps in knowledge regarding the pharmacology of drug release from particulate-based LA injectable suspensions are explored.
112 citations
TL;DR: Results showed that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform, and showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and treatment with histamine induced changes in the localization of tight and adherens junction-associated proteins.
Abstract: We developed a microfluidic model of microcirculation containing both blood and lymphatic vessels for examining vascular permeability. The designed microfluidic device harbors upper and lower channels that are partly aligned and are separated by a porous membrane, and on this membrane, blood vascular endothelial cells (BECs) and lymphatic endothelial cells (LECs) were cocultured back-to-back. At cell-cell junctions of both BECs and LECs, claudin-5 and VE-cadherin were detected. The permeability coefficient measured here was lower than the value reported for isolated mammalian venules. Moreover, our results showed that the flow culture established in the device promoted the formation of endothelial cell-cell junctions, and that treatment with histamine, an inflammation-promoting substance, induced changes in the localization of tight and adherens junction-associated proteins and an increase in vascular permeability in the microdevice. These findings indicated that both BECs and LECs appeared to retain their functions in the microfluidic coculture platform. Using this microcirculation device, the vascular damage induced by habu snake venom was successfully assayed, and the assay time was reduced from 24 h to 30 min. This is the first report of a microcirculation model in which BECs and LECs were cocultured. Because the micromodel includes lymphatic vessels in addition to blood vessels, the model can be used to evaluate both vascular permeability and lymphatic return rate.
98 citations
Cites background from "Recent advances in lymphatic target..."
...Studies on drug-delivery systems (DDSs) have previously investigated the enhanced permeation and retention effect, which is caused by the presence of imperfect tumor blood vessels and poor lymphatic drainage in tumor tissues [54,55], and a lymphatic system-targeted DDS has also attracted research attention [56]....
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TL;DR: Based on the available data, the lipid nanoparticles makes this drug delivery systems as one of the promising delivery systems and will be a solution to the formulation scientist and complies the key objectives of Green chemistry and sustainable chemistry.
76 citations
References
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3,457 citations
TL;DR: It is shown that the penetration and efficacy of the larger micelles could be enhanced by using a transforming growth factor-β inhibitor to increase the permeability of the tumours.
Abstract: Drug-loaded polymeric micelles with a diameter of 30 nm can penetrate poorly permeable tumours to achieve an antitumour effect.
2,026 citations
TL;DR: In this article, the authors investigate whether nanoparticles can be used as a vaccine platform by targeting lymph node-residing dendritic cells via interstitial flow and activating these cells by in situ complement activation.
Abstract: Antigen targeting and adjuvancy schemes that respectively facilitate delivery of antigen to dendritic cells and elicit their activation have been explored in vaccine development. Here we investigate whether nanoparticles can be used as a vaccine platform by targeting lymph node-residing dendritic cells via interstitial flow and activating these cells by in situ complement activation. After intradermal injection, interstitial flow transported ultra-small nanoparticles (25 nm) highly efficiently into lymphatic capillaries and their draining lymph nodes, targeting half of the lymph node-residing dendritic cells, whereas 100-nm nanoparticles were only 10% as efficient. The surface chemistry of these nanoparticles activated the complement cascade, generating a danger signal in situ and potently activating dendritic cells. Using nanoparticles conjugated to the model antigen ovalbumin, we demonstrate generation of humoral and cellular immunity in mice in a size- and complement-dependent manner.
1,158 citations
Journal Article•
TL;DR: This work investigates whether nanoparticles can be used as a vaccine platform by targeting lymph node–residing dendritic cells via interstitial flow and activating these cells by in situ complement activation, and demonstrates generation of humoral and cellular immunity in mice in a size- and complement-dependent manner.
Abstract: Reference EPFL-CONF-160860View record in Web of Science Record created on 2010-11-30, modified on 2017-05-12
977 citations