4 replies to this topic

[Anthony_Loera]

Many folks on the board know we are the only folks who have successfully produced dry powder nano particle resveratrol. Other folks claim nano resveratrol in a liquid emulsion with ethanol and other additives, however these folks know that it can't be measured through xray/light diffraction in this form, while dry nano resveratrol can be measured and confirmed properly... and then used in all sorts of applications, while liquid emulsions are limited.

Anyway,

For some reason I was reading the COPD Resveratrol summary here tonight:
http://www.scienceda...41030221643.htm

Just for kicks, I decided to bring out some of the nano-particle resveratrol out to play.

I brought together the following:

1- Airial "The physician's choice" MQ5800 Compressor Nebulizer System. (It's my son's, and we never used it)
2- Dry Nano Resveratrol. This was made to research it's production costs at RevGenetics, as a dry powder. We are the only company in the world that makes pure dry powder in this fashion. Yes the particle size average is under 50nm.
3- 1 bottle of publix spring water. (Publix is the name of a large food store chain here in Miami Florida).
4- A 1/8 measuring teaspoon

So here I am fumbling with the machine, and finally get all the plastic pieces together.

My first try: The first time, just the powder folks.
I just drop in a 1/8 teaspoon of res into the plastic nebulizer, and turn it on... powder everywhere. Oh Great... . As you can see, I never actually used one of these suckers.

My second try: I realize that nebulizers need liquid <smacks head>.
Ok, so I don't have DMSO, and I am not sure I want ethanol or DMSO in this thing... safety of course. I pull out a water bottle I bought a publix. I mix 1/8 teaspoon of dry nano-resveratrol with 1/8 teaspoon of plain old H20. I know that normal resveratrol cannot dissolve easily in water... but what the heck this stuff is incredibly small compared to normal res, so I try it anyway. It looks milky after mixing it... then I put it in the nebulizer (cleaned of course)... it sputters, and although I do see some of it coming out... it definitly doesn't look like the smokey particles from when a normal nebulizer is used... nope.

My third try: I decide to add more water
I put in two parts water to my one part nano-resveratrol. Drop it in and turn on the machine...and Presto!
I was now looking at a steamy/smokey cold vapor coming from the machine.

Now if only a large pharmaceutical contacted me to provide them with the nano-particle resveratrol, boy would that make my day... but for now, I am settling on a good quiet night.



Cheers
A

P.S. Before you ask... no we cannot sell this dry nano resveratrol to anyone for inhalation (sorry guys) If we do start putting it out on the market, it could only be used as a supplement taken by mouth capsule form or a powder that would be added to your favorite nutritional drink... FDA rules and all that.

Edited by Anthony_Loera, 27 January 2012 - 04:20 AM.

[niner]

GSK sells a dry powder inhaler. It's one of their formulations of Advair. It's a steroid, which is hydrophobic and tissue permeable, and a beta agonist that is water soluble. The thing that worries me about inhaled resveratrol is that it lies in between these types of molecules. It is mostly insoluble in water, but it isn't hydrophobic enough to show good permeability. In fact, the permeability is rather poor. So what would happen if you repeatedly inhaled it? My fear is that it would clog up the alveoli. At 50nm, it could easily travel beyond the point where cilia could remove it. Would it gradually be absorbed? Would it cause problems just by virtue of being a solid in the alveolar sac? I don't know. In the best case scenario, it would act as a novel non-steroidal anti-inflammatory, or might have other useful properties. It's the worst case scenario that I worry about here. That might be pretty ugly. This is a case where I would definately want to do some animal experiments first.

[Anthony_Loera]

Niner,

as always, I appreciate your posts and agree that animal tests would need to be done to assure the cilia could remove it and/or it dissolves in an appropriate amount of time. Repeating inhaling it, without knowing it can be cleared by your system (or what amount of time it takes to clear the system) is why it would need to be tested and prescribed by a physician.

Having said that...
I truly hope this get's tested really soon by a major pharma... and we get contacted to supply the material. I honestly believe it works at this point (I think you be able to guess why), but only proper testing would settle safety parameters such as dosage, and say... time between dosage... if the nano-res was even cleared properly by your system at all.

Very important considerations that only a pharma's research could help the public with.
A

Edited by Anthony_Loera, 27 January 2012 - 05:19 AM.

[Anthony_Loera]

Here's something that appears more recent that uses mice and a nebulizer:

(I am going to see if I can get this study to check on what was found in lung tissues)

Published: 1 June 2011

Resveratrol has protective effects against airway remodeling and airway hyperreactivity in a murine model of allergic airways disease

http://www.pathobiol...iewArticle/7134

Background: New therapies for asthma which can address three main interrelated features of the disease, airway inflammation, airway remodeling and airway hyperreactivity, are urgently required. Resveratrol, a well known red wine polyphenol has received much attention due to its potential anti-aging properties. This compound is an agonist of silent information regulator two histone deacetylases and has many effects that are relevant to key aspects of the pathophysiology of asthma including inflammation, cell proliferation and fibrosis. Therefore, resveratrol may offer a novel asthma therapy that simultaneously inhibits airway inflammation, and airway remodeling which are the main contributors to airway hyperreactivity and irreversible lung function loss. Methods: We evaluated the effects of systemic resveratrol treatment in a murine model of chronic allergic airways disease which displays most of the clinicopathological features of severe human asthma. Wild-type Balb/c mice with allergic airways disease were treated with 12.5 mg/kg resveratrol or vehicle control. Airway inflammation was assessed by bronchoalveolar lavage fluid cell counts and histological examination of lung tissue sections. Further, remodeling was assessed by morphometric analysis and lung function was assessed by invasive plethysmography measurement of airway resistance and dynamic compliance. Results: Mice treated with resveratrol exhibited reduced tissue inflammation as compared to vehicle treated mice (p<0.05). Additionally, resveratrol treatment resulted in reduced subepithelial collagen deposition as compared to vehicle treated mice (p<0.05) and attenuated airway hyperreactivity (p<0.05). Conclusions: These novel findings demonstrate that treatment with resveratrol can reduce structural airway remodeling changes and hyperreactivity. This has important implications for the development of new therapeutic approaches to asthma.

Edited by Anthony_Loera, 27 January 2012 - 09:21 PM.

[Anthony_Loera]

Ok...

From the study.. I think the dose is a bit excessive, but here it is:
"An established model of OVA-induced chronic allergic airways disease was used as previously described (25, 26). This model includes many of the pathological features of human asthma including increased allergic responses indicated by increased immunoglobulin E against OVA (OVA-specific IgE),AHR,and remodeling changes such as epithelial remodeling, goblet cell metaplasia, and subepithelial collagen deposition (fibrosis). However, it does not display smooth muscle hyperplasia (25, 26). Briefly, mice were sensitized with 10 mg of grade V OVA (Sigma Chemical, St. Louis,MO) and 1mg of aluminumpotassium sulfate adjuvant (alum) in 500 ml saline i.p on day 0 and 14 and then challengedwithnebulized 2.5%(w/v)OVAin saline 3 days per week for 6 weeks to establish AAD. Ovalbumin-exposed mice were treated with resveratrol (OVA-RV, n15) or vehicle control (OVA-VEH, n15) intraperitoneally following each OVA nebulization (3 days per week for 6 weeks). A third group of mice, sensitized with saline/alum on days 0 and 14 and nebulized with saline 3 days per week for 6 weeks (n15), served as additional controls. Resveratrol (Sigma Chemical) was used at a dose of 12.5 mg/kg in 20% ethanol/0.9% saline, which is known to be biologically active and has been used widely in experimental murine models of disease with minimal toxicity (27, 28)."



Conclusions:
"We investigated the potential of resveratrol treatment for asthma using a chronic murine model of allergic airways disease. We assessed the effect of the drug in preventing airway remodeling and suppressing AHR. Our findings indicate that resveratrol suppressed AHR and inhibited the development of subepithelial bronchial fibrosis. This effect on fibrosis involved reduced TGFb protein expression in the airways of mice treated with resveratrol. In our study we did not see significant reduction in BAL fluid inflammatory cell numbers although we did we see modest reduction in lung tissue inflammation infiltrate in the chronic allergic airways disease mice treated with resveratrol. This likely reflects the treatment regimen used and the chronic ovalbumin model that exhibits only moderate inflammation and eosinophilia compared to the acute and subacute models of allergic airways disease (29). One of the major features of the chronic allergic airways disease model is the relatively high AHR to methacholine. In the current study we found that resveratrol resulted in lower AHR at high concentrations of methacholine. The AHR is the most important clinical endpoint in asthma; increased AHR is not only symptomatic of asthma but is a correlate of disease severity (GINA guidelines) and can be used for diagnosis and monitoring the disease. Whilst we only demonstrate modest evidence of action on airway inflammation, resveratrol had a powerful anti-remodeling activity, particularly in airway subepithelial fibrosis. Airway fibrosis is an important pathological process in many airway diseases including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and scleroderma. Fibrotic remodeling of the basement membrane, the formation of the lamina reticularis, is pathognomonic of asthma and correlates with severity in endobronchial biopsies from asthma sufferers (35). Fibrosis in the lamina reticularis, lamina propria, and serosa contributes to the overall thickness of the airway wall that impacts AHR (36, 37). Furthermore, extracellular matrix is deposited between airway smooth muscle cells in asthma (38). Extracellular matrix not only contributes to increased muscle mass for AHR but matrix components such as collagen I have been shown in vitro to promote airway smooth muscle cell proliferation (39). Airway fibrosis in asthma is due to extracellular matrix deposition by fibroblasts and is accompanied by differentiation of myofibroblasts, activated fibroblasts with contractile properties, and a smooth muscle actin expression. These processes are regulated by TGFb, a potent profibrotic cytokine. The TGFb is hypersecreted by epithelial cells and fibroblasts in the airway as well as the influx of inflammatory cells including eosinophils in asthma (40). We found significantly less TGFb protein in mice treated with resveratrol than in ovalbumin control mice. In the current study resveratrol was administered intraperitoneally over a 6 week period. The dose used was efficacious without any side effect in the rodent model as assessed by histopathology of representative organ samples, animal welfare scorings, and bodyweight (data not shown). However, the current study has the caveat that resveratrol was used to prevent disease rather than reverse established disease. Nevertheless, we have provided in vivo evidence for an anti-fibrotic action of resveratrol in inflammatory obstructive lung disease and suppression of AHR in a model of chronic allergic airways disease. Our findings add to the recent literature establishing the anti-fibrotic effects of resveratrol in a wide range of organ systems, providing evidence of key anti-aging properties. Overall, the findings highlight that a dietary and pharmacological approach using resveratrol may represent safe and timely treatment for asthma and lung disease that target a central aspect of airway remodeling and may subvert steroid resistance."


I think this would be great for a clinical trial.

A