Development and characterization of lysine-methotrexate conjugate for enhanced brain delivery

Singh, Vijay Kumar; Subudhi, Bharat Bhusan

doi:10.3109/10717544.2014.984369

Cited by 31 publications

(24 citation statements)

References 51 publications

(46 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many targeted approaches for MTX have been exploited to reduce adverse effects, improve bioavailability and maximize treatment effect (Jain et al, 2015 ; Farjadian et al, 2016 ; Guo et al, 2018 ; Liu et al, 2017 ). Earlier paper demonstrated that MTX-mediated nanoparticle drug delivery system would be a predominant targeted anticancer chemotherapeutic formulation (Chen et al, 2014 ; Li et al, 2017a , 2017b ; Singh & Subudhi, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

et al. 2018

View full text Add to dashboard Cite

Combination chemotherapy is widely exploited for suppressing drug resistance and achieving synergistic anticancer efficacy in the clinic. In this paper, the nanostructured targeting methotrexate (MTX) plus pemetrexed (PMX) chitosan nanoparticles (CNPs) were developed by modifying methoxy polye (thylene glycol) (mPEG), in which PEGylation CNPs was used as stealth nanocarriers (PCNPs) and MTX was employed as a targeting ligand and chemotherapeutic agent as well. Studies were undertaken on human lung adenocarcinoma epithelial (A549) and Lewis lung carcinoma (LLC) cell lines, revealing the anti-tumor efficacy of nanoparticle drug delivery system. The co-delivery nanoparticles (MTX-PMX-PCNPs) had well-dispersed with sustained release behavior. Cell counting kit-8 (CCK8) has been used to measure A549 cell viability and the research showed that MTX-PMX-PCNPs were much more effective than free drugs when it came to the inhibition of growth and proliferation. Cell cycle assay by flow cytometry manifested that the MTX-PMX-PCNPs exhibited stronger intracellular taken up ability than free drugs at the same concentration. In vivo anticancer effect results indicated that MTX-PMX-PCNPs exhibited a significantly prolong blood circulation, more tumoral location accumulation, and resulted in a robust synergistic anticancer efficacy in lung cancer in mice. The results clearly demonstrated that such unique synergistic anticancer efficacy of co-delivery of MTX and PMX via stealth nanocarriers, providing a prospective strategy for lung cancer treatment.

show abstract

Section: Introductionmentioning

confidence: 99%

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Recently, Singh et al prepared a methotrexate (MTX)-lysine conjugate to enhance MTX brain uptake through the endogenous transport system of lysine in the BBB. The favorable pharmacokinetics and biodistribution of the MTX-lysine conjugate demonstrated the selective brain transport of this prodrug 60 . However, taking into account the size of amino acids, this kind of prodrug approach could only be suitable for small molecules.…”

Section: Current Strategies To Deliver Drugs Into the Brainmentioning

confidence: 98%

Current Strategies for Brain Drug Delivery

2018

View full text Add to dashboard Cite

The blood-brain barrier (BBB) has been a great hurdle for brain drug delivery. The BBB in healthy brain is a diffusion barrier essential for protecting normal brain function by impeding most compounds from transiting from the blood to the brain; only small molecules can cross the BBB. Under certain pathological conditions of diseases such as stroke, diabetes, seizures, multiple sclerosis, Parkinson's disease and Alzheimer disease, the BBB is disrupted. The objective of this review is to provide a broad overview on current strategies for brain drug delivery and related subjects from the past five years. It is hoped that this review could inspire readers to discover possible approaches to deliver drugs into the brain. After an initial overview of the BBB structure and function in both healthy and pathological conditions, this review re-visits, according to recent publications, some questions that are controversial, such as whether nanoparticles by themselves could cross the BBB and whether drugs are specifically transferred to the brain by actively targeted nanoparticles. Current non-nanoparticle strategies are also reviewed, such as delivery of drugs through the permeable BBB under pathological conditions and using non-invasive techniques to enhance brain drug uptake. Finally, one particular area that is often neglected in brain drug delivery is the influence of aging on the BBB, which is captured in this review based on the limited studies in the literature.

show abstract

“…Possible improvements in brain availability and scope of application were investigated by reversible conjugation with lysine by an amide linkage in order to exploit the endogenous transport system of lysine at BBB (47). Possible improvements in brain availability and scope of application were investigated by reversible conjugation with lysine by an amide linkage in order to exploit the endogenous transport system of lysine at BBB (47).…”

Section: Conjugationmentioning

confidence: 99%

“…The anticancer drug MTX has poor permeability across the BBB making it unsuitable for brain tumor application. Possible improvements in brain availability and scope of application were investigated by reversible conjugation with lysine by an amide linkage in order to exploit the endogenous transport system of lysine at BBB (47). The structure of prodrug was confirmed by mass spectrometry and stability and metabolic studies suggested that the conjugate was stable at physiological pH and could release MTX slowly to the brain.…”

Section: Conjugationmentioning

confidence: 99%

Advances in drug delivery to high grade gliomas

Fròsina

2016

Brain Pathology

View full text Add to dashboard Cite

If cancer is hard to be treated, brain cancer is even more, caused by the inability of many effective drugs given systemically to cross the blood brain and blood tumor barriers and reach adequate concentrations at the tumor sites. Effective delivery of drugs to brain cancer tissues is thus a necessary, albeit not sufficient, condition to effectively target the disease. In order to analyze the current status of research on drug delivery to high grade gliomas (HGG-WHO grades III and IV), the most frequent and aggressive brain cancers, a literature search was conducted in PubMed using the terms: "drug delivery and brain tumor" over the publication year 2015. Currently explored drug delivery techniques for HGG include the convection and permeabilization-enhanced deliveries, drug-releasing depots and Ommaya reservoirs. The efficacy/safety ratio widely varies among these techniques and the success of current efforts to increase this ratio widely varies as well.

show abstract

Development and characterization of lysine-methotrexate conjugate for enhanced brain delivery

Cited by 31 publications

References 51 publications

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

Development of dual-drug-loaded stealth nanocarriers for targeted and synergistic anti-lung cancer efficacy

Current Strategies for Brain Drug Delivery

Advances in drug delivery to high grade gliomas

Contact Info

Product

Resources

About