Improved delivery through biological membranes. XLI. Brain-enhanced delivery of chlorambucil

Bodor, Nicholas; Venkatraghavan, Vasudevan; Winwood, David; Estes, Kerry S.; Brewster, Marcus E.

doi:10.1016/0378-5173(89)90313-x

Cited by 27 publications

(9 citation statements)

References 23 publications

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“…The parent drug is a carboxylic acid; therefore CDSs can be obtained by using either N-hydroxyethylnicotinamide or various aminoalcohols as linkers. 225 A CDS obtained with 2-aminoethanol as a linker between the drug and T (60, Fig. 25) produced a sustained level of 59 in the brain after i.v.…”

Section: Anticancer Drugsmentioning

confidence: 99%

Targeting drugs to the brain by redox chemical delivery systems

2000

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Section: Anticancer Drugsmentioning

confidence: 99%

Targeting drugs to the brain by redox chemical delivery systems

2000

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“…32,33 The CDS approach relying on this targetor moiety is a general approach that can, and has been applied to a wide variety of drug classes to increase brain delivery, improve brain targeting, and/or provide sustained CNS effects. [7][8][9][10][11] Following his graduation, Marcus continued to work in the brain-delivery field by extending this redox-targetor CDS concept to many other molecules including, for example, tryptamine, 34 progestins, 35 estrogens, and their derivatives [36][37][38][39] chlorambucil, 40 sulfonamides, 41 adenosine, 42 ribavirin, 43 zidovudine, [44][45][46] LY231617 (an antioxidant), 47 and dexamethasone. 48 Among these CDSs, estradiol-CDS (E 2 -CDS, Estredox) reached the most advanced developmental stage, phase I/II clinical trials, and Marcus made invaluable contributions to its development.…”

Section: Estradiol-cds and Other Brain-targeting Cdss (1983-2006)mentioning

confidence: 99%

“…He became involved in the use of various modified CDs to improve the formulation of a wide range of compounds (1988-2014). 92 These include several drugs modified as their brain-targeted CDS redox derivative, such as the anticancer drug chlorambucil, 40 azydothymidine, 93,94 b-lactam antibiotics, 95 zidovudine, 46,96 propofol, 97 and ganciclovir. 98 It also included other drugs (i.e., not brain-targeted CDSs), such as the important steroidal analgesic alfaxalone, 99,100 doxorubicin, 101 dexamethasone, 102 carbamazepine, 103,104 and other antiepileptics, 105 as well as pregnanolone and pregnenolone.…”

Section: Estradiol-cds and Other Brain-targeting Cdss (1983-2006)mentioning

confidence: 99%

Brain-Targeting Chemical Delivery Systems and Their Cyclodextrin-Based Formulations in Light of the Contributions of Marcus E. Brewster

Buchwald

Bodor

2016

Journal of Pharmaceutical Sciences

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Here, we present a brief review of brain-targeting chemical delivery systems (CDSs) and their cyclodextrin-based formulations. It is dedicated to the memory of Marcus E. Brewster (1957-2014) and highlights those aspects where he made particularly valuable contributions. During the first two decades of his scientific career that were dedicated to these fields (1978-1997), Marcus was involved in the development of several brain-targeted redox compounds, including design, activity assays, physicochemical characterization, computational modeling of theoretical aspects, and development of cyclodextrin-based formulation for increased stability and water solubility, as well as preclinical and clinical testing. CDSs are designed to provide site-specific or site-enhanced delivery through sequential, multistep enzymatic, and chemical transformations. Brain-targeting CDSs incorporate a redox targetor that undergoes enzymatic transformation resulting in a drastic change in physicochemical properties. They can not only increase central nervous system access by making the molecule more lipophilic and enabling its diffusion through the blood-brain barrier, but they can also provide more sustained release by "locking" it behind the blood-brain barrier by subsequently converting it into a hydrophilic intermediate. The origins of the concept (Pro-2-PAM, berberine), one of the most important representative (estradiol-CDS), and the introduction of 2-hydroxypropyl-β-cyclodextrin for improved formulations are discussed in detail.

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“…Specifically, dihydropyridinium salt delivery systems have successfully achieved targeted penicillin delivery to the central nervous system (26). Other pyridinium salts have been used to selectively facilitate drug transport across the brain–blood barrier and dermis via enzymatic hydrolysis (27–30). CTAB and related surfactants have enhanced drug absorption by various strains of Gram‐negative and Gram‐positive bacteria (31).…”

mentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of β‐Lactam Antibiotic‐Based Imidazolium‐ and Pyridinium‐Type Ionic Liquids

Cole

El‐Zahab

et al. 2011

Chem Biol Drug Des

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We herein report the preparation and investigation of antibacterial activity of biocidal ionic liquids (ILs) consisting of cationic imidazolium or pyridinium and an anionic β-lactam antibiotic. The antibacterial properties were quantified by measuring the minimum inhibitory concentration and minimum bactericidal concentration against Escherichia coli O157:H7, Klebsiella pneumoniae, Staphylococcus aureus, and Enterococcus faecium. In general, the ILs had improved antibacterial activity than their parent materials, whether individually or in combination. In 83% of the experiments, the ampicillin ILs (Amp-ILs) had better antibacterial activities than their quaternary halide parent materials, whereas in 92% of the experiments, Amp-ILs outperformed the commercially available sodium ampicillin salt. Amp-ILs had up to 43 times improved antibacterial activity than sodium ampicillin. Overall, when normalized for ampicillin content, ILs had greater antimicrobial activity against E. coli O157:H7, K. pneumoniae, S. aureus, and E. faecium than sodium ampicillin alone.

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Improved delivery through biological membranes. XLI. Brain-enhanced delivery of chlorambucil

Cited by 27 publications

References 23 publications

Targeting drugs to the brain by redox chemical delivery systems

Targeting drugs to the brain by redox chemical delivery systems

Brain-Targeting Chemical Delivery Systems and Their Cyclodextrin-Based Formulations in Light of the Contributions of Marcus E. Brewster

Design, Synthesis, and Biological Evaluation of β‐Lactam Antibiotic‐Based Imidazolium‐ and Pyridinium‐Type Ionic Liquids

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