Dmso as a drug vehicle
What is it about insulin for example that prevents it from being carried through the skin? NOTE 2: I hope this is not considered a duplicate of this question as the answer is specific to the transport of small molecules. Quote taken from the review 1 and which is also duplicated in Jacob's "canonical DMSO" book 2p. There is some evidence to suggest that DMSO can increase diffusion through the stratum corneum by disruption of the barrier function.
This probably occurs through aprotic interactions with intercellular lipids and may also include reversible distortion of lipid head groups that produce a more permeable packing arrangement. DMSO may also play a role in partitioning as well by forming solvent microenvironments within the tissue that can effectively extract solute from vehicle.
Finally, DMSO can have a profound solubilizing effect on less soluble agents in a variety of vehicles, increasing penetration simply by delivering a higher concentration to the membrane barrier. The reported membrane thinning and, in particular, pore formation provide a credible molecular-level explanation of how DMSO promotes permeation of molecules, particularly those of hydrophilic nature, through lipid membranes as observed experimentally.
From what I understand, DMSO paves the way for bigger molecules, such as steroids, making inner skin layers and underlying tissue reversibly accessible, sometimes even on nanoscale level. For the precise mechanism I think it is worth reading through the entire paper 3.
The Journal of clinical and aesthetic dermatology5 9 The Journal of Physical Chemistry B35— DOI Sign up to join this community. The best answers are voted up and rise to the top. Home Questions Tags Users Unanswered. How does DMSO act as a carrier for transdermal transport of large molecules? Ask Question. Asked 3 years, 2 months ago.
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Viewed 1k times. Active Oldest Votes. How is that helpful? When you boil it down key phrases are "aprotic interactions with My sense is that so many possibilities means ideas being thrown about without people really knowing the answer. If so, why use jargon to cover that reality? In laymans terms DMSO is acting as a solvent for the molecules making up the skin, disrupting their function.Steelskull raid
Am I right? Andselisk said it's "making inner skin layers and underlying tissue reversibly accessible" which is quite clear. If you don't understand the jargon then learn more about chemistry and refrain from such comments in the future.
Nevertheless, I did not present myself as an expert but instead asked, "Am I right?Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.
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We comply with the HONcode standard for trustworthy health information - verify here. Skip to Content. Another commonly used name is DMSO. In addition, dimethyl sulfoxide administered topically, orally, or intravenously has not been proven to be effective in the treatment of musculoskeletal disorders; diseases of connective tissue e. Absorption: Dimethyl sulfoxide is absorbed systemically following topical application. Biotransformation: Metabolized to dimethyl sulfone and dimethyl sulfide.
The other metabolite, dimethyl sulfide, is eliminated via breath and through the skin. Studies in hamsters, rats, and mice have shown that dimethyl sulfoxide causes teratogenic effects when administered intraperitoneally at high doses of 2. In addition, studies in rabbits have shown that dimethyl sulfoxide causes teratogenic effects when administered topically at doses of 5 grams per kg of body weight for the first 2 days, then 2.
However, in another study using rabbits, dimethyl sulfoxide was not shown to cause any abnormalities when administered topically at doses of 1. Furthermore, dimethyl sulfoxide was not shown to cause reproductive problems in hamsters, rats, and mice when administered in oral or topical doses.
Breast-feeding It is not known whether dimethyl sulfoxide is excreted in breast milk and problems in humans have not been documented; however, dimethyl sulfoxide is systemically absorbed. Pediatrics Appropriate studies on the relationship of age to the effects of this medicine have not been performed in the pediatric population.
Geriatrics Appropriate studies on the relationship of age to the effects of this medicine have not been performed in the geriatric population. However, no geriatrics-specific problems have been documented to date. Treatment of overdose If dimethyl sulfoxide is accidently ingested: To decrease absorption: Emesis should be induced. Measures that may be considered include gastric lavage and administration of activated charcoal. To enhance elimination: Forced diuresis should be considered. It is to be instilled directly into the bladder using a catheter or an asepto syringe.
Prior to inserting the catheter, application of an analgesic lubricant such as lidocaine jelly to the urethra is recommended to avoid spasm. Strength s usually available U. Protect from strong light. Federal Register. Dimethyl sulfoxide DMSO.Dimethyl sulfoxide is a colorless liquid derived as a by-product from wood pulp in the production of paper.
This colorless liquid found immediate application as a polar, aprotic solvent miscible with water and able to dissolve an enormous catalog of polar and nonpolar small molecules. It is presently scarcely used in dermatology, but given its useful properties as a penetration-enhancing solvent excipient and active anti-inflammatory pharmaceutical agent, dimethyl sulfoxide has the potential to be used in a much broader capacity.
The authors review the history, chemistry, and clinical utility of dimethyl sulfoxide as it pertains to dermatology. Topical agents have long been employed for surface therapies in dermatology. In addition to the diagnostic advantage afforded by visual signs present on readily accessible surfaces, in many cases, treatment can be directly applied to pathological lesions.
The development of neat drug substances working only on the surface is trivial; no need to penetrate any physiological barriers, solubilize in carrier vehicles, or stabilize in specialized chemical mixtures.
A step up from these most primitive therapies are the simple solutions, suspensions, and creams placed directly on affected areas that need only provide suitable surface delivery for the active agent. An armamentarium of novel formulation techniques has evolved for the treatment of deeper lesions or for the delivery of therapeutic agents that cannot be easily applied as rudimentary preparations.
The authors discuss the history, chemistry, and clinical utility of one such agent—dimethyl sulfoxide DMSO —a common, controversial substance with a storied past. Its use in dermatology is now limited. It is most commonly used as a keratolytic agent in conjunction with potassium hydroxide KOH to enhance visualization of fungal hyphae when ascertaining the presence of dermatophyte infection.
However, DMSO has the potential for much broader applications. Like so many modern medicinal products, DMSO traces its roots to the nascent German chemical industry of the mid-to-late 19th century. In the search for cheaper, more efficient methods to produce paper from wood pulp, a process was developed in which its by-products included a variety of sulfide-containing compounds.
These malodorous sulfides were converted to less-noxious sulfoxides, including DMSO. Since the s, DMSO has been extensively studied in the chemical literature. It is a preferred solvent for a host of named reactions and benefits from both hard and soft nucleophile properties.Onedrive knjige pdf
It is routinely used as a mild oxidant in a variety of synthetic schemes and has gained great utility for the study of carbanion chemistry. It was noted that DMSO spilled onto the hands would quickly cause a distinctive garlic taste on the tongue, which led to the systematic investigation of DMSO as a transport agent that could be used to deliver small molecules through skin and mucosa.
Organ preservation studies by Dr. Stanley Jacob in the early s led to subsequent pharmacotherapeutic investigations by his own lab and a host of other research groups. There are more than 1, publications on the merits of DMSO, but it fell out of favor in the s after the United States Food and Drug Administration FDA became much more rigid following the discovery of limb defects in children born from mothers taking thalidomide.
Other than the generic version approved inthis remains the only approved human indication. There are a variety of veterinary DMSO preparations, both alone and in combination with steroids, approved by the FDA originally in the s and currently sold under a range of brands including Domoso, Domoso Gel, Synsac, and Synotoc Otic. Jacob 2 discovered in fact rediscovered, as it was already known in the German chemical literature as described above that DMSO effectively penetrates the skin, an observation he first made in a series of nine patients treated for dermatitis using topical DMSO.
Biology Stack Exchange is a question and answer site for biology researchers, academics, and students. It only takes a minute to sign up. And, in this case, why is the viability of the untreated condition lower than the vehicle DMSO alone? If you are looking for information on Coronaviruses, we have prepared this FAQ with information on what is on topic on this site and links to some reputable external resources. Sign up to join this community. The best answers are voted up and rise to the top.
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Home Questions Tags Users Unanswered. Asked 2 years, 10 months ago.Status of river ganga and action plan to improve its water quality in phase-ii (down stream-unnao to
Active 2 years, 10 months ago. Viewed 3k times. CKM 7, 13 13 silver badges 28 28 bronze badges. Sokviseth Sokviseth 53 1 1 silver badge 4 4 bronze badges. And based on the above graph, why do the graph of Vehicle is higher than None? The most probably reason is just biological variance, from your two different samples.
Benefits of DMSO
Also note that the SD which doesnt make a lot of sense for 2 samples anyway for the vehicle control is very large. The treated samples are pretty much different from them. If it's indeed a measure of viability, basically you're saying your drugs are dissolved in DMSO, and you want to see the effect of the drugs vs. Your goalhowever, is you actually want to say that the DMSO had no effect so you can see the pure effect of your drugs.
The p-value between your none and vehicle is like 0.It was the production of cheaper paper that led to the discovery of this colorless liquid in the 19th Century, but it was its characteristic of being able to dissolve a large number of polar and non polar small molecules that made this a great solvent in the research world.
When it was discovered that DMSO had the unusual chemical characteristic of carrying small molecules through membranes, the use of this solvent was expanded in the clinical and scientific. In the s Dr. This information spread and pharmaceuticals quickly started to push the use of DMSO as a solvent of their drugs. Knowing the toxicity effects this solvent may have on our model organisms, we conduct studies to determine tolerance levels before we begin an investigation.
We counted the number of pupae by Day 6 and observed how our npc1 mutants start to become sensitive after 0. Figure 3: This graph shows how ngly1 mutants start to show significant development delay after 2. Moreover, dissolving drugs in Ethanol has the disadvantage of being very volatile, which can lead to variable drug concentrations. However, we are unaware of systematic small molecule studies in flies where the ideal average dose was identified. This is something we would like to conduct with a small library of bioactive compounds.
Matrix Medical Communications, Sept. Samaras, and Edson Carias. Helix Magazine, 28 July Landes Bioscience, 9 July DMSO, NCBI, 9 Jan. Reference: -Capriotti, Kara, and Joseph A.Ritetemp wall heater parts
Search for:. Find a Cure. Follow us.Dimethyl sulfoxide DMSO is an amphipathic molecule that displays a diversity of antitumor activities. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is regulated by the transcription factor AP We found that DMSO can significantly inhibit cancer cell invasion, migration, proliferation, and colony formation capabilities through upregulation of HLJ1 in a concentration-dependent manner, whereas ethanol has no effect.
Targeted induction of HLJ1 represents a promising approach for cancer therapy, which also implied that DMSO may serve as a potential lead compound or coordinated ligand for the development of novel anticancer drugs.
Dimethyl sulfoxide DMSO; CH 3 2 SO is an amphipathic molecule that has a highly polar domain and two apolar methyl groups, making it soluble in both aqueous and organic media . Although its biological effects have not been clearly defined, it is used extensively in a variety of fields.
It is commonly used as a very efficient solvent for water-insoluble compounds in biological studies and a cryoprotectant of cultured cells . In addition, it is also popularly used as a vehicle for drug therapy for various diseases, including dermatological disorders amyloidosis gastrointestinal diseases traumatic brain edema musculoskeletal disorders pulmonary adenocarcinoma rheumatologic diseases and schizophrenia . DMSO also had been used for treatment of leukemia for several years as it induces cellular differentiation, causing leukemia cells to lose their proliferative properties .
Furthermore, DMSO has been found to arrest the cell cycle of lymphoid cell lines at the G1 phase and it can effectively inhibit capillary tube formation through MMP-2 suppression . With its high relapse and low cure rates, lung cancer is the most common cause of cancer mortality and incidence in the world .
In a previous study, we screened a series of human lung adenocarcinoma cell lines with varying invasion capabilities by microarray and identified a panel of metastasis-related genes including the human liver DnaJ-like protein HLJ1, also known as DNAJB4 .
We subsequently demonstrated that HLJ1, a tumor suppressor in non-small cell lung cancer NSCLCcan inhibit lung cancer proliferation, anchorage-independent growth, motility, invasion, tumorigenesis, and cell cycle progression. Furthermore, the endogenous transcriptional expression of HLJ1 is upregulated via enhancer activator protein-1 AP-1 binding to its promoter Yin-Yang-1 YY1 with the coactivator p .
Due to its tumor suppressor properties, HLJ1 is a potential target for anticancer therapy . Additionally, HLJ1 is a novel substrate of caspase-3 and is degraded at a late stage of apoptosis .
Therefore, clarifying the molecular mechanisms involved in HLJ1 upregulation may be important for anticancer therapy. Indeed, curcumin, an active component of the spice turmeric, has been reported to inhibit lung cancer cell invasion and metastasis through HLJ1 . However, whether any other small molecules or chemicals can effectively modulate HLJ1 expression is still unknown. For instance, it is involved in the suppression of ICAM-1 expression in a rat model of peritonitis sepsis  and in the respiratory syncytial virus RSV -induced production of IL-8 in A epithelial cells .
CL1—5 cells were seeded onto well plates and cultured for 48 h with various concentrations of DMSO 0, 0. The detailed procedures were as described previously Wang et al. Experiments were performed three times in triplicate. All transfections were performed in triplicate in 6-well plates, and the detailed protocol has been described in previous studies . Briefly, CL1—5 cells were seeded for 24 h prior to transfection. All constructs were confirmed by restriction endonuclease digestion and DNA sequencing.
The cells were incubated in transfection mixture for 4 h and then harvested after 44 h in culture with or without DMSO treatment. Luminescence was measured with a Victor 3 multilabel counter Perkin-Elmer. Each experiment was repeated at least three times in duplicate.
The migratory capability of the CL1—5 cells treated with or without DMSO was assessed using the wound healing approach as described previously . The number of cells migrating into the cell-free zone was determined by counting under a light microscope. All experiments were performed in triplicate.Preclinical evaluation of drug-like molecules requires their oral administration to experimental animals using suitable vehicles. We studied the effect of oral dosing with corn oil, carboxymethyl cellulose, dimethyl sulfoxide, and polysorbate on the progression of Mycobacterium tuberculosis infection in mice.
Infection was monitored by physical survival time and body weight and bacteriological viable counts in lungs parameters. Compared with water, corn oil significantly improved both sets of parameters, whereas the other vehicles affected only physical parameters. Every year, progressive infection with Mycobacterium tuberculosis leads to approximately 8 million new tuberculosis TB cases and 3 million deaths worldwide.
This alarming situation emphasizes the need for new drugs against TB 28 Evaluation of the in vivo efficacy of a new drug candidate in a suitable animal model is a critical step in determining whether it will enter the preclinical and clinical development phases When infected with a high number of CFU of M. Thus, the mouse model can provide information on lead molecule activity that can be extrapolated to humans 8 Outbred mice, particularly Swiss mice, are used for in vivo assays for anti-TB activity because of their heterogeneity, which is akin to that of the human population 3.
For in vivo evaluations, a lead molecule is preferably administered as a solution or suspension by the oral route 1which is an important requirement for its successful development as a new drug.
However, if the molecule is highly hydrophobic, then edible oils such as corn or peanut oil are used as vehicles For moderately hydrophobic molecules, certain solubilizing agents, such as carboxymethyl cellulose CMCdimethyl sulfoxide DMSOand polysorbate Tween 80can be added to the aqueous dosing vehicle 23 The influence of dosing vehicles on the progression of disease in animal models, if any, is an important consideration for in vivo evaluation of test molecules.
There is hardly any information available on whether these vehicles themselves could modulate the disease process, thereby influencing the outcome of the evaluation of the drug candidates.What Is DMSO?
This is particularly important in cases of chronic infections, such as TB, where treatments are given to the animals for long periods of time 612 We therefore studied the effect that some of the vehicles themselves could exert on the progression of M. Study parameters were physical, i. Corn oil was administered undiluted, whereas dilutions of CMC 0. Each group was given water or the other vehicles separately 0.
The progress of infection was monitored in the control untreated mice by determining numbers of viable bacilli CFU on day 1 postinfection and then at weekly intervals Fig. Numbers of CFU in the lungs of mice from each experimental vehicle-treated group were determined on day Progression of M.
However, a significant difference was not observed between MST mean survival time of all animals in a group of the water-fed Survival, average body weight, and bacterial load in lungs of M. All three MSTs were higher than those observed with water and oil. With respect to oil, only CMC showed a significantly greater decline in the body weight 3.
Linoleic acid has been found to inhibit mycobacteria in vitro 1529 ; thus, it could also produce the same effect in vivo. Among the three, administration of DMSO resulted in much improved physical parameters.
Measurement of survival time or body weight of animals is an appropriate, cost- and time-effective criterion to assess the progression of infection and to evaluate new drugs against M. Our results, however, show that weight loss and MST may not be reliable criteria and that determination of bacterial load in the infected organs is a true measure of infection.
Moreover, in a previous screening for TB-induced weight loss, some active compounds or drugs possessing anabolic properties could have affected the results In conclusion, the vehicles used for oral dosing of test molecules can influence physical as well as bacteriological parameters in mice infected with M.
We are grateful to Director, Central Drug Research Institute, Lucknow, India, for providing necessary facilities and support to carry out the work.
- Fpm 1998, vol. 4, no. 1, pp. 233-244
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