Nanostructure-Templated Control of Drug Release From Peptide Amphiphile Nanofiber Gels.
Nanostructure-templated control of drug release from peptide amphiphile nanofiber gels.
Filed under: Drug and Alcohol Rehabilitation
Soft Matter. 2012 Apr 7; 8(13): 3586-3595
Matson JB, Newcomb CJ, Bitton R, Stupp SI
High aspect ratio peptide nanofibers have potential as biodegradable vehicles for drug delivery. We report here the synthesis of four self-assembling peptide amphiphiles (PAs) containing a lysine ?-amine-derivatized hydrazide that was systematically placed at different positions along the backbone of the peptide sequence C(16)V(2)A(2)E(2) (where C(16) = palmitic acid). Hydrazones were formed from each hydrazide by condensation with the solvatochromic dye 6-propionyl-2-dimethylaminonaphthalene (Prodan), which is typically used to probe cell membranes. All four compounds were found to self-assemble into nanofibers, and Prodan release was measured from filamentous gels prepared by screening PA charges with divalent cations. Near zero-order release kinetics were observed for all nanofibers, but release half-lives differed depending on the position of the fluorophore in the PA sequence. Dye release kinetics were rationalized through the use of cryogenic transmission electron microscopy, small-angle X-ray scattering, fluorescence spectroscopy, fluorescence anisotropy, circular dichroism, and partition coefficient calculations. Relative release rates were found to correlate directly with fluorophore mobility, which varied inversely with packing density, degree of order in the hydrophobic PA core, and the ?-sheet character of the peptide.
HubMed – drug
Current progress of RNA aptamer-based therapeutics.
Filed under: Drug and Alcohol Rehabilitation
Front Genet. 2012; 3: 234
Zhou J, Bobbin ML, Burnett JC, Rossi JJ
Aptamers are single-stranded nucleic acids that specifically recognize and bind tightly to their cognate targets due to their stable three-dimensional structure. Nucleic acid aptamers have been developed for various applications, including diagnostics, molecular imaging, biomarker discovery, target validation, therapeutics, and drug delivery. Due to their high specificity and binding affinity, aptamers directly block or interrupt the functions of target proteins making them promising therapeutic agents for the treatment of human maladies. Additionally, aptamers that bind to cell surface proteins are well suited for the targeted delivery of other therapeutics, such as conjugated small interfering RNAs (siRNA) that induce RNA interference (RNAi). Thus, aptamer-siRNA chimeras may offer dual-functions, in which the aptamer inhibits a receptor function, while the siRNA internalizes into the cell to target a specific mRNA. This review focuses on the current progress and therapeutic potential of RNA aptamers, including the use of cell-internalizing aptamers as cell-type specific delivery vehicles for targeted RNAi. In particular, we discuss emerging aptamer-based therapeutics that provide unique clinical opportunities for the treatment various cancers and neurological diseases.
HubMed – drug
Frequencies of 23 functionally significant variant alleles related with metabolism of antineoplastic drugs in the chilean population: comparison with caucasian and asian populations.
Filed under: Drug and Alcohol Rehabilitation
Front Genet. 2012; 3: 229
Roco A, Quiñones L, Agúndez JA, García-Martín E, Squicciarini V, Miranda C, Garay J, Farfán N, Saavedra I, Cáceres D, Ibarra C, Varela N
Cancer is a leading cause of death worldwide. The cancer incidence rate in Chile is 133.7/100,000 inhabitants and it is the second cause of death, after cardiovascular diseases. Most of the antineoplastic drugs are metabolized to be detoxified, and some of them to be activated. Genetic polymorphisms of drug-metabolizing enzymes can induce deep changes in enzyme activity, leading to individual variability in drug efficacy and/or toxicity. The present research describes the presence of genetic polymorphisms in the Chilean population, which might be useful in public health programs for personalized treatment of cancer, and compares these frequencies with those reported for Asian and Caucasian populations, as a contribution to the evaluation of ethnic differences in the response to chemotherapy. We analyzed 23 polymorphisms in a group of 253 unrelated Chilean volunteers from the general population. The results showed that CYP2A6*2, CYP2A6*3, CYP2D6*3, CYP2C19*3, and CYP3A4*17 variant alleles are virtually absent in Chileans. CYP1A1*2A allele frequency (0.37) is similar to that of Caucasians and higher than that reported for Japanese people. Allele frequencies for CYP3A5*3(0.76) and CYP2C9*3(0.04) are similar to those observed in Japanese people. CYP1A1*2C(0.32), CYP1A2*1F(0.77), CYP3A4*1B(0.06), CYP2D6*2(0.41), and MTHFR T(0.52) allele frequencies are higher than the observed either in Caucasian or in Japanese populations. Conversely, CYP2C19*2 allelic frequency (0.12), and genotype frequencies for GSTT1 null (0.11) and GSTM1 null (0.36) are lower than those observed in both populations. Finally, allele frequencies for CYP2A6*4(0.04), CYP2C8*3(0.06), CYP2C9*2(0.06), CYP2D6*4(0.12), CYP2E1*5B(0.14), CYP2E1*6(0.19), and UGT2B7*2(0.40) are intermediate in relation to those described in Caucasian and in Japanese populations, as expected according to the ethnic origin of the Chilean population. In conclusion, our findings support the idea that ethnic variability must be considered in the pharmacogenomic assessment of cancer pharmacotherapy, especially in mixed populations and for drugs with a narrow safety range.
HubMed – drug
Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection.
Filed under: Drug and Alcohol Rehabilitation
J Pharmacol Pharmacother. 2012 Jul; 3(3): 276-8
George J, Sharma A, Dixit R, Chhabra N, Sharma S
Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN) are rare but serious dermatologic disorders. These grave conditions present as medical emergency, requiring prompt diagnosis and management. These are often drug induced and various groups of drugs, such as sulfa drugs, NSAIDS, etc., have been implicated as to cause TEN. Fluconazole is a commonly used drug with mild side effects. TEN caused by fluconazole is rare, and till now only few cases have been reported in the literature. We present a case of TEN in a human immunodeficiency virus infected man following fluconazole therapy in view of its rare occurrence.
HubMed – drug
Untreated: Volume 2 “Newcummers” – Untreated is an original, comedy web series that explores the wild and wonderfully bizarre world of life inside the walls of a pint-sized drug and alcohol rehabilitation center. Filtered through the eyes of our colorful core of characters, we discover that sobriety and sanity do not necessarily go hand in hand. Furthermore, this mixed up bag of nuts seems to only have one thing in common: that they are all completely unready, totally unwilling and entirely Untreated! Contact Demian Slade & Quincy Rose at: [email protected] Credits: Executive Produced, Created & Written by: Demian Slade Produced, Edited & Directed by: Quincy Rose Director of Photography: Marcin Nadolny Starring: Demian Slade as Joe Zach Tiegen as Doug Jenn Gulotta as April Elizabeth Hendrix as Shorty Brown Albert Malafronte as Dr. Stan Quincy Rose as Rich Anonymous as Candy Co-Executive Producer: Susan Martinson Assistant Director & Assistant Camera: Alex Rinks Sound Mixer & Boom Operator: Rob Ellenberg Special Thanks: Betsy Phillips Maddy the Cat Katie the Dog Amza Moglan Noah Alexander Tara Tomicevic “Untreated” and all episodes and clips related are the sole property of Demian Slade & Quincy Rose. copyright 2011 Demian Slade & Quincy Rose: [email protected]
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