EPR: Evidence and fallacy

Nichols, Joseph W.; Bae, You Han

doi:10.1016/j.jconrel.2014.03.057

Cited by 692 publications

(445 citation statements)

References 152 publications

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“…[104,205] Furthermore, in other cancers like multiple myeloma and metastatic breast cancer, the therapeutic efficacy was equivalent to that of standard clinical therapies. [206,207] The main advantage of the Doxil in the therapy of solid tumors is the reduced cardiotoxicity, which is the adverse side effect caused by doxorubicin, as a result of the limited doxorubicin accumulation in heart. Nevertheless, Doxil have shown other side effects like hand-foot syndrome due to the extravasation into the skin facilitated by the prolonged circulation properties of Doxil.…”

Section: Cancer Nanomedicines From the Clinical Medicine Perspectivementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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Explosive growth of nanomedicines continues to significantly impact the therapeutic strategies for effective cancer treatment. Despite the significant progress in the development of advanced nanomedicines, successful clinical translation remains challenging. As cancer nanomedicine is a multidisciplinary field, the fundamental problem is that the knowledge gaps stem from different vantage points in the understanding of cancer nanomedicines. The complexities and heterogenecity of both nanomedicines and cancer are further demanding the integration of highly diverse expertise to develop clinically translatable cancer nanomedicines. This progress report aims to discuss the current understanding of cancer nanomedicines between different research areas in terms of nanoparticle engineering, formulation, tumor patho-physiology and clinical medicine, as well as to identify the knowledge gaps lying at the interface between the different fields of research in nanomedicine. Here we also highlight for the necessity to harmonize the multidisciplinary effort in the research of nanomedicines in order to bridge the knowledge and to advance the full understanding in cancer nanomedicines. A paradigm shift is needed in the strategic development of disease specific nanomedicines in order to foster the successful translation into clinic of future cancer nanomedicines.

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Section: Cancer Nanomedicines From the Clinical Medicine Perspectivementioning

confidence: 99%

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Balasubramanian

Liu

Hirvonen

et al. 2017

Adv Healthcare Materials

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show abstract

“…The EPR effect has been extensively defined in all types of tumor, without the tumor with less vasculature such as pancreatic and prostate tumors [20]. Though, a current review of the clinical studies showed that the effect of encapsulated medication is slightly advanced than the drug which is not encapsulated, a result of these differences has been got in vivo trails using animal models [21]. Actually, The EPR effect depends on the type of cancer and irregular vascularity of cancer; it may be decreased due to high fluid pressure in the interstitial space and low blood flow in cancerous tissue.…”

Section: The Epr Effectmentioning

confidence: 99%

Liposomes and Nanotechnology in Drug Development: Focus On Pancreatic Cancer

Malik¹,

Jin²,

Raheem³

et al. 2017

JGPLD

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Pancreatic cancer usually has high morbidity and mortality and rests one of the most challenging cancers to treat. 5 years survival rate is less than 6 percent overall for people with pancreatic cancer, because of very late diagnosis and absence of effective treatment. In a western world, pancreatic tumor is the fourth most common cause of death in a western world. The pancreatic tumor needs selective delivery of drugs to target cells, with no side effects is major goals of the recent investigations for the real treatment of the pancreatic tumor. Medication which targets pancreatic tumor cells specially and carriers which deliver medications to specific cells which are quickly dividing, development of these kind drugs is considered as magic for the management of pancreatic cancer. In latest years, liposomes and nanotechnology can show a vital character in the treatment of pancreatic tumor. Liposomes contain multiple characteristics, such as the ability to protect the material from degradation, the capacity for encapsulating many materials and capability for delivering materials intracellularly fusion with plasma membrane. Nanoparticles as a carrier offer a new style of delivery of the medications to target cells of a tumor and allow drugs for the binding to tumor cell membrane, to cytoplasmic and to nuclear receptor sites. It delivers high medication concentrations to specific cells with few side effects to other normal tissues. The general importance of this evaluation is to increase overall understanding of development of the therapeutic nanomedicine for the treatment of pancreatic tumors, agents delivered by nanoliposomes, liposomal nanomedicine in targeting cancer and safety issues.

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“…Such selective accumulation or passive targeting, which works especially good with tumors due to the lack of lymphatic drainage there, is currently known as enhanced permeability and retention (EPR) effect (Peer et al, 2007;Maeda 2010;Nichols & Bae, 2014). In addition, HES-10-HCPT conjugate showed better long circulating effect in vivo, which can promote the accumulation of 10-HCPT in tumor.…”

Section: Tissue Distribution Studymentioning

confidence: 99%

Well-defined hydroxyethyl starch-10-hydroxy camptothecin super macromolecule conjugate: cytotoxicity, pharmacodynamics research, tissue distribution test and intravenous injection safety assessment

Zhao

2016

Drug Delivery

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10-Hydroxy camptothecin (10-HCPT) is an antitumor agent effective in the treatment of several solid tumors but its use is hampered by poor water solubility, low lactone stability, short plasma half-life and dose-limiting toxicity. These limits of 10-HCPT had been overcome by our group through preparing super macromolecule prodrug: 10-HCPT-hydroxyethyl starch (HES) conjugate. In this study, we mainly evaluated in vitro and in vivo behavior of the prodrug, containing cytotoxicity assay, pharmacodynamics study, vascular irritation test, hemolysis experiment and tissue distribution test of rats. The irritation test results achieved much lower irritation than the commercial injection. The tissue distribution results showed that HES-10-HCPT conjugate increased significantly the 10-HCPT concentration in the tumor, liver and spleen site, whereas decreased the drug concentration in the heart and kidney. The hemolysis effect of the prepared conjugate was not obvious. The pharmacodynamics results indicated that HES-10-HCPT prodrug had a better antitumor efficiency against mice with H22 tumor than the commercial injection, and the inhibition ratio of tumor was 85.2% and 31.1%, respectively at the same dosage. These findings suggest that HES-10-HCPT prodrug is a promising drug delivery system providing improved good injection safety, greater tolerance and antitumor effect.

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EPR: Evidence and fallacy

Cited by 692 publications

References 152 publications

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Bridging the Knowledge of Different Worlds to Understand the Big Picture of Cancer Nanomedicines

Liposomes and Nanotechnology in Drug Development: Focus On Pancreatic Cancer

Well-defined hydroxyethyl starch-10-hydroxy camptothecin super macromolecule conjugate: cytotoxicity, pharmacodynamics research, tissue distribution test and intravenous injection safety assessment

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