Delivery of epidrugs

Bahhaj, Fatima el; Dekker, Frank J.; Martinet, Nadine; Bertrand, Philìppe

doi:10.1016/j.drudis.2014.03.017

Cited by 18 publications

(22 citation statements)

References 131 publications

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“…Additional advantages of nanoparticle-based drug delivery systems may include the ability to target cancer (active, passive, and enhanced permeability and retention [EPR] effect), greater drug stability and lower drug concentrations during administration. All of these advantages have been found to result in lower systemic toxicity and a higher therapeutic index [15, 67, 68]. Targeting has been exploited in cancer therapies and can be passive or active.…”

Section: Delivery Of Epigenetic Drugsmentioning

confidence: 99%

“…Nanoparticles, liposomes, and other delivery vectors take advantage of this property and the poor lymphatic drainage characteristic of tumors to achieve greater accumulation in tumor tissue than elsewhere in the body [69, 70]. Active targeting seeks to exploit an extracellular or intracellular mechanism or the increased acidity of a tumor environment (due to increased levels of lactic acid as a product of glycolysis) [15]. Certain proteins or receptors are overexpressed in cancer cells and these can be exploited by conjugating a ligand to the nanoparticle or other delivery vector [71].…”

Section: Delivery Of Epigenetic Drugsmentioning

confidence: 99%

“…Certain proteins or receptors are overexpressed in cancer cells and these can be exploited by conjugating a ligand to the nanoparticle or other delivery vector [71]. Cellular uptake of the delivery system could be by several receptor-mediated endocytotic pathways including clathrin-dependent, clathrin-independent macropinocytosis, and caveole-meditaed [15, 18]. The mechanism of uptake will depend on the size, shape, and surface characteristics such as charge and hydrophobicity of the vector [72].…”

Section: Delivery Of Epigenetic Drugsmentioning

confidence: 99%

“…Several methods of enhancing delivery include a delivery system such as different nanocarriers, altering the chemical structure of the drug (pro-drugs), and administration in combination with another drug are aimed at increasing effectiveness of these drugs [15]. Choosing a form of delivery vector includes taking into account properties of the drug or agent to be encapsulated such as the polarity of the drug (some popular epigenetic drugs such as decitabine and 5-azacytidine are hydrophilic), molecular weight of the drug, pharmacokinetics and biodistribution, and effective dose and time of treatment needed at the diseased site [16-18].…”

Section: Introductionmentioning

confidence: 99%

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Advancements in the delivery of epigenetic drugs

Cramer

Adjei

Labhasetwar

2015

Expert Opinion on Drug Delivery

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Introduction Advancements in epigenetic treatments are not only coming from new drugs but from modifications or encapsulation of the existing drugs into different formulations leading to greater stability and enhanced delivery to the target site. The epigenome is highly regulated and complex; therefore it is important that off-target effects of epigenetic drugs be minimized. The step from in vitro to in vivo treatment of these drugs often requires development of a method of effective delivery for clinical translation. Areas covered This review covers epigenetic mechanisms such as DNA methylation, chromatin remodeling and small RNA mediated gene regulation. There is a section in the review with examples of diseases where epigenetic alterations lead to impaired pathways, with an emphasis on cancer. Epigenetic drugs, their targets and clinical status are presented. Advantages of using a delivery method for epigenetic drugs as well as examples of current advancements and challenges are also discussed. Expert opinion Epigenetic drugs have the potential to be very effective therapy against a number of diseases, especially cancers and neurological disorders. As with many chemotherapeutics, undesired side effects need to be minimized. Finding a suitable delivery method means reducing side effects and achieving a higher therapeutic index. Each drug may require a unique delivery method exploiting the drug's chemistry or other physical characteristic requiring interdisciplinary participation and would benefit from a better understanding of the mechanisms of action.

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Section: Delivery Of Epigenetic Drugsmentioning

confidence: 99%

Section: Delivery Of Epigenetic Drugsmentioning

confidence: 99%

Section: Delivery Of Epigenetic Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Advancements in the delivery of epigenetic drugs

Cramer

Adjei

Labhasetwar

2015

Expert Opinion on Drug Delivery

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“…On the other hand, the lower antitumor efficacy of free SAHA should be attributed to the destruction of hydroxamic acid under physiological conditions. 18,19,54 In addition, the changes in the body weight of mice were monitored during the period of study ( Figure 9B). There were no obvious changes of body weight in all the treatment groups.…”

mentioning

confidence: 99%

A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

Han¹,

Wang²,

Wu³

et al. 2016

IJN

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Targeting the epigenome with advanced delivery strategies for epigenetic modulators

Guha,

Jagadeesan,

Pandey

et al. 2024

Bioengineering & Transla Med

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Epigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth. Currently, a considerable amount of research is focused on discovering new drug molecules to combat the existing research gap in epigenetic drug therapy. A novel and efficient delivery system can be established as a promising approach to overcome the drawbacks associated with the current epigenetic modulators. Therefore, formulating the existing epigenetic drugs with distinct encapsulation strategies in nanocarriers, including solid lipid nanoparticles, nanogels, bio‐engineered nanocarriers, liposomes, surface modified nanoparticles, and polymer–drug conjugates have been examined for therapeutic efficacy. Nonetheless, several epigenetic modulators are untouched for their therapeutic potential through different delivery strategies. This review provides a comprehensive up to date discussion on the research findings of various epigenetics mechanism, epigenetic modulators, and delivery strategies utilized to improve their therapeutic outcome. Furthermore, this review also highlights the recently emerged CRISPR tool for epigenome editing.

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Delivery of epidrugs

Cited by 18 publications

References 131 publications

Advancements in the delivery of epigenetic drugs

Advancements in the delivery of epigenetic drugs

A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy

Targeting the epigenome with advanced delivery strategies for epigenetic modulators

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