A Review on Effective Use of Gold Nanoparticles Formed Using the Bioactive of Fruits Peels Encapsulated with Various Drugs for The Treatment of Gouty Arthritis or Hyperuricemia

Abstract

Gold nanoparticles are used for the treatment of gouty arthritis or hyperuricemia in the context of encapsulation with various or variety of different types of drugs to lower the blood serum urate level (<0.54 mg/dl). Here we are using pineapple fruit peel extract for the bioactive solution and formation of {pi AuNPs} is done. These encapsulations also contain the drugs which controls the gouty flares or attacks which are major problem of this disease which the patients suffer the most. Luteolin, probenecid, colchicine and citric acid are to be as the major drug constituents of the encapsulation of nanoparticles. there three drugs are used are herbally extracted through various different process according to the need of the substance it be collected and one product that is probenecid is used semi- synthetic in which major part is natural and then its ids reacted with the synthetic chemical reaction to achieve final product. The result we are expecting or theory on the result we are giving is that this combination much helpful than the single drug therapy by any individual drug. And according many literatures reviews this novel combination will definitely cure gout faster.

Keywords

Introduction

Gout is an acute and chronic type of disease in which the major and only causative agent is the uric acid crystals which can create problem by any mechanism of the formation of crystals and the deposition in any place of the body and create various problem and the gout is the major one of the them. In gout the urate crystal is collected in the blood vessels and he synovial membrane of the joints and the tophi of human body at any place of the body but the major reason which is affected is the joints and tophi of the legs joint or called knee joint and the ankle joints because the amount of the synovial fluid is very high in these two places which is best medium for the urate crystals to accumulate.  In gout the major problem is of flares or attack which are very painful and last for large period of time as these attacks can last for the weeks and even for the months. In acute gout condition the intensity of flares is relatively low but the pain intensity is much higher and the local NSAIDs like colchicine is used but in chronic gout condition flares intensity is very high and the problem is not localized the pain may impact legs, hands even though head also but the anti-inflammatory drug in the chronic gout condition are not permitted or not used by the doctors but the use of those drugs are more needed for those patients then the  patient of the acute gout conditions.  Gold nanoparticles have many aspectual uses in the pharmaceutical industry or in the drug delivery system for human’s and sometimes some animals also which are not meant to be loose. Here I am discussing or presenting a use of gold nanoparticle for very efficient disease which can be treated in better way with the use of gold nanoparticle due to its high intensity, large surface area and nontoxic effects to the human body. for the treatment of gouty arthritis or hyperuricemia gold nanoparticles encapsulated with different ratio combination of drug (S)is used. the encapsulated drugs are probenecid { a uricosuric drug which minimize the urate absorption in tubules of nephron and increase the secretion of uric acid from the body} , allopurinol { this is a enzyme inhibitor which inhibit the xanthine oxidase enzyme by which the synthesis of the uric acid itself decreases in the body}, colchicine and citric acid { this work as a common drug for treatment as it is inhibitor also and uricosuric also and even though it perform the function of NSAIDs also. 

Names of each drug we have encapsulated.

1. Probenecid 
2. Colchicine 
3. Luteolin 
4. Citric acid 

Listed drugs information 

1. Colchicine 

Colchicine is the active compound used in the acute gout now the days in relief of the pain happen due to the movement of the uric acid crystals deposition induce lymphocytes movement in the membrane of the joints inside and outside as the body immunity mechanism process lymphocytes are the first line mechanism of the inflammation and present where body cycle disturb and this accumulation of lymphocytes causes pain in the acute gout condition. 

The use of colchicine or NSAIDs in the chronic gout or hyperuricemia condition is not publishes properly as the chronic gout condition is precursor of the acute gout condition so the pain or gout attacks are more frequent and heavier in chronic gout so the use of NSAIDs are advisable in the chronic gout condition. Colchicine is both synthetic and herbal compound  in the treatment of the gout condition Whether it is chronic or acute but the effect of synthetic cholchine is more and it show adverse effects like the activation of H.pyroli { increase the secretion of the hydrochloric acid in the stomach which causes the peptic ulcer in  the stomach which is very serious and dangerous outcome} , it attacks the kidney glomerulus and the nephron activity and make them slow and the main disadvantage of the synthetic NSAIDs is the mental disturbance and body resistivity. Herbal approaches are safe this time and the sensitivity toward herbal drugs is now more this time 

2. Luteolin 

Luteolin is the herbal alternative for the allopurinol.  Allopurinol   is the primary first line drug therapy for the patients dealing with the gout disease either it is acute or chronic allopurinol is substitute in patients’ treatment plan. allopurinol active compound is the oxypurinol which is formed when allopurinol is substituted in the body by any route of administration whether it is oral or parental. as the allopurinol follow the first order of mechanism after substitution it goes in liver and then digested and change its form as allopurinol is not a drug it is compound which contain oxypurinol as the therapeutic. although allopurinol can’t even digest and can’t be eliminated from the body in its primary form and if the allopurinol is not digested by liver the accumulation of allopurinol can even do kidney failure conditions. Oxypurinol is the enzyme inhibitor as it stops the uric acid cycle in between and the formation of soluble uric acid is not permitted in the presence of this drug.

3. Probenecid 

Probenecid is the ancient drug used for the treatment for the chronic gout condition or gouty arthritis. this is the anciently synthetic drug no herbal precursor of this drug is not available in the market as it works in that state so synthesis. this is an uricosuric drug which is meant to lower the accumulated urate crystals concentration in the joints knee or tophi where the accumulation is happen this drug do not treat the gout condition only the intensity of the gout attacks and the pain id lower by the use of this drug.

4. Citric acid 

Citric acid an ecofriendly type of acid rather than any harmful effects it is the type which is highly useable by human beings in any sector of benefits either it is pharmaceutical, food industry, cosmetics etc. in gout treatment citric acid plays an initial role in lowering the urate concentration in human body. Citric acid has high concentration of antioxidants which rapidly helpful in lowering the dissolved uric acid in blood flow itself which is the end product of the purine metabolism and can’t be extracted from the kidney. So simply citric acid low the dissolve uric acid of the blood.

 Source used of these briefed drugs  

1. Colchicine 

Here the plant name Colchicum autumnale is use to obtain colchicine herbally.  For the better extraction concentration, we are using the seed of this plant as they contain highest concentration of colchicine even though lower part of the plant also contains the colchicine but the concentration much lower than an he seeds concentration the common name of colchicum autumnale is (suranjan). the extract content of seeds is range between 0.5% to 0.8%.   

2. Citric acid 

The most common acid of daily use in the lifestyle of human beings obtained from the citrus limon commonly called lemon. the concentration of citric acid in lemon juice ranges between 5-6% of total lemon juice 

3. Probenecid 

In the drug research bank, no herbal source of the probenecid is available. Now what we can do is that we can use it semi synthetic which is less toxic than proper synthesis chemical drug. for semi synthesis we follow to steps:

3. 1. First, we extract the base of probenecid herbally which is benzoic acid, for herbal extraction of benzoic we use fruit vaccinium symplocifolium which commonly called as (karonda). 
   2. Second ally we perform sulphonating and amidation reaction in the extract so, we obtain probenecid as a product 
4. Luteolin 

Luteolin is present in the extract of the celery seed in the lower concentration but effective when the proper extraction method is used to extract the specific component form the extract. the concentration, measures  form 0.8-1.0 mg / g. 

Why the herbal sources are focusing    

The thing in now the time is toxicity. High  usage of synthetic drugs and the amount of toxicity present in the lifestyle of human beings by various reason and the use of medicines is very. Eventough  in the world every single person is suffering form any kind of diseased or any kind of normal problems but the use of the medicine is mandatory. Wheater the problem is big or small as the immunity capacity of human beings is reduced with very rapid down flow . accordingly environment issues the toxicity to human is very much higher and to make a positive effect the use of synthetic medicine is also there so , we are focusing on the herbal source for the treatment of the disease  not in newer way but only by extracting the some component form the plant or their fruits or their seeds and any other part of the plant and formulating a combination of drugs which are more effectively safe for the humans as herbal drugs do not  intrept the metabolism and catabolism of the human internal environment and the herbal drugs relatively cheaper than the synthetic, even  if they are expensive but safe to use and can be taken for  long time and do not show resistivity as compared to the synthetic drugs. 

Mechanism of action of listed drugs

1. Colchicine 

Mechanism of colchicine,  it simply makes a barrier for the movement of lymphocytes inside and outside in the synovial membrane by making tubulin protein ligand and stop the intervention to tubulin secreting inflammatory chemicals like interleukins, cytokinin’s, TNF alpha etc. due to intervention in secration of inflammatory agents’ anti-inflammatory compounds concentration steadily increase and decreases the pain in the gouty arthritis and gout flares.

2. Luteolin 

It  is the enzyme inhibitor type of drug and plays a first line mechanism in the cure and relief in the gout condition as first problem of any disease is there problem causative substance and the disease causative agent in the gout are the uric acid crystals which formed from the dissolved uric acid in blood when the dissolved uric acid came outside the blood vessel dur to excessive concentration and the process of simple diffusion the crystals formation starts to happen and then accumulation and the luteolin ais one which stops the uric acid  formation in blood by making interventions in the uric acid cycle. Luteolin inhibit the xanthine oxidase enzyme which is a crucial and the last enzyme of the uric acid formation because it convert xanthine into uric acids. Xanthine is the last product of all type of metabolism which form uric acid at last whether it is metabolism of nucleotide or any other purine metabolism. 

3. Probenecid 

It is the ancient time drug used in the medication of the gout treatment but the probenecid is the drug which do not treat gout not even cure it. it only lowers the urate crystals in the body which cause gout as serious problem. The Thung probenecid do is it lower or stops the uric acid absorption in the tubules of the nephron in the kidney and increase the secretion of the urate crystals by breaking down them inti the small pieces and even by dissolving the urate crystals and let them to pass from the kidney followed by urination. 4.

Citric acid 

It is majorly an efficient drug in the gout treatment if it works efficiently with high efficiency as it is the full of antioxidants which are responsible of the breakroom of uric acid itself in the blood and making a bi-product which can be easily eliminated from the body but we can’t high amount of citric acid as our blood ph. will get disturb and the major problems are create resides solving one problem.

What the side effects these drugs show when use proper synthetic or in wrong dose 

1. Probenecid 

As of studies done on the probenecid the the harmful effects or probenecid is numerous and useful effects are also numerous but here, we list with harmful effects that are more dangerous than the anything related to gout the it includes the heart failure, kidney failure, mental retardation and many more effects that the secondary but these primary effects are too than the gout. 

2. Allopurinol 

Here we are using luteolin alternative to allopurinol as allopurinol is total synthetic drug which majorly cause the kidney failure and heart related diseases in the primary phase and the allopurinol is Firstline treatment drug to be substituted in the body of the gou6 patients.  3. Colchicine 

Its major side effects are the resistivity toward the NSAIDs which is very harmful for the other disease in which the anti-inflammatory drugs are too be used and the high concentration use of the NSAIDs leads to the secretion of the H.pyroli which later cause the peptic ulcers and create a huge problem related to digestion and the body growth and survival. 

4. Citric acid 

It’s a natural product eventually don’t show any side effect the only side effect is high concentration can lead to the acidity in the blood which leads to many more diseases in the same frequency of the time. 

Formation of gold nanoparticles from the bioactive of the pineapple 

1. Formation of the bioactive containing solution of pineapples 
2. Formation of the gold nanoparticles using chemical and bioactive solution 
3. Separation of the formed  particles 
4. Drying of the collected particles 

• To form bioactive solution of the pineapple 
  • collect the waste peels of the fruit
  • cut the down in the small pieces 
  • boil them in the distilled water at controlled temperature 
  • filter the solution and cool down at room 
  • temperature or even low temperature 
• Formation of gold nanoparticles
  • Take a sufficient amount of, HAucl4 .3H2O mix with the bioactive solution
  • A considerable ratio is 6:1 respectively 
  • Mix both the liquid with continuous stirring 
  • A color change and precipitation form start to happen and this is what reaction go 
  • Centrifuge the solution at high rpm for 30 min 
• Separation of formed particles 
  • Filter the solution and collect the residue on filter paper 
  • Wash the collected residue 2-3 times with distilled water 
• Drying of the collected particles 
  • Scatter the collected particles on the watch glass 
  • Dry heat them for at least 40 min or whatever time is suitable 

CONCLUSION

The conclusion we are proposing the use of gold nanoparticle encapsulated with the luteolin, citric acid, colchicine and probenecid is very effective full for the use of the gout disease or hyperuricemia disease to prevent the flares that occurs in the gout disease

RESULTS AND DISCUSSION

The result we are proposing is the use of the combination rater than the use of single or individual doses of the various drugs at different times as according to the literature reviews the efficiency of the individual drugs are far less than the combination and the combination’s show synergistic effects of combined drug and increased once another effect and bioavailability. The adverse effects of the drugs are also can be reduced by using the combination of drugs as the colchicine and the probenecid are far more toxic if used for the lob period of the time with no safety measure but when used with allopurinol and citric acid their effects will be less. This combination possesses two drugs for the same problem and to increase their working efficiency by maintain its concentration gradient in blood circulation. In future the study about this combination will further results a new genre of medicine in the history of the gout.

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