Nanotechnology has become revolutionized approach in the advanced drug delivery system in recent years. It is the science that formulate the nanoparticles of specific size range 1-1000nm of diameters. These particles reveal such characteristics that are closely related to their features. In recent times nanoparticle production is successful tool to overcome the problems that are common side effects of other drug delivery systems like instability, degradation of active ingredient, toxic effects, inadequate absorption and poor biological activity. (Conte. R et al.
, 2016) Nanoparticles are useful for targeted drug delivery by which any therapeutic agent can be delivered to specific site. The specific site may be a specific type of cell or even smaller than cell that may include cell organelles.
As compare to other drug development systems the nanotechnology show distinctive characteristics for target sites. As larger molecules can not easily approach such smaller targets. Recent advance studies has developed some carriers that improve pharmacokinetic parameters of nanoparticles. (Liang Liu et al.
, 2013 )
In recent times, pesticides were rarely used for prevention purposes. But now a days pesticides have become essential and easily accessible ingredient in the field of agriculture. According to some researchers infectious diseases cause less mortalities as compare to these poisoning agents. In most of suicidal attempts poisoning of these easily reachable agents is common. Cypermethrin(CYP) is a synthetic insecticide that belongs to class pyrethroid . It is commonly used insecticide worldwide. It is notorious to provoke GI and skin poisoning.(Goutham et al., 2016)
CYP is also effective at domestic levels.
Its probability of toxicity is less in mammals but quickly metabolized and produces free radicals. These free radicals are responsible of oxidative stress, lipid peroxidation and tissue damage in many vital organs of body. Nephrotoxicity of these agents is due to disturbance of biomolecule levels and ultimately cause loss of kidneys weight.(Saima et al., 2016)
Different plant products like some fruits and vegetables contain biologically active constituents that have many important physiological and pharmacological effects. Flavonoids are abundantly found in many edible plants. They are largely utilized by humans and have many biological actions. Quercetin(QU) is one of member of bioflavonoids that have several pharmacological actions in the body. QU has prominent activity against many microbial infections, oxidants, inflammation as well as allergens. Some researchers ensure that QU have potential to stop proliferative changes in cancer cells. (Shaista et al., 2014)
QU has ability to protect different organs(kidneys, heart and liver). Oxidative stress is the main cause of nephrotoxicity. QU has prominent antioxidant activity by involving enzymatic and non-enzymatic systems.( O.A. Almaghrabi et al. 2014)
For targeted drug delivery an efficient carrier is required. Carrier should must have some features that make it compatible with drug as well as with the body. There is variety of polymers that are used as carrier in Nano-biotechnology such as chitosan(CHO).
CHO is biologically active, cheap and less toxic polymer suitable for carrier for hydrophobic drug like QU. CHO itself has therapeutic potential for some health problems. CHO has effects like antimicrobial, antioxidant and antitumor. Chitosan nanoparticles and quercetin loaded chitosan nanoparticles both have efficacy against the renal toxicity and oxidative stress. (Mosaad A. et al., 2016)The aim of present study is to assess renal toxicity of cypermetharin and nephroprotective effects of quercetin.
Preparation and characterization of quercetin loaded chitosan nanoparticles.
To investigate nephroprotective effect of quercetin loaded chitosan nanoparticles in vivo.
Pakistan is an agrarian country number of plants are grew there. Some crops are exported to different other countries which includes tobacco, cotton and rice majorly and some fruits as well. Without use of pesticides tobacco cultivation is not possible. Because at some points of tobacco cultivation provide suitable conditions for pests. Without use of pesticides crop will yield nothing. But long term exposure to these extremely dangerous substances can cause serious health issues for farmers.( Dilshad.A et al., 2008)
The excessive use of pesticides causing pollution of air and contaminating environment with residues of pesticides.(Goutham.S.P et al., 2016) According to study residues of the pesticide like CYP were obtained from the blood samples of the farmers but no clinical signs were appeared. Pesticides cause changes at biochemical initially then proceeds towards serious toxicities. (Dilshad.A et al., 2008)
The chances of toxicity of CYP in workers of pesticide industries are as critical as in farmers dealing with them. Unfortunately , the intensity of toxicity related injuries and effectiveness of remedies are not determined yet. The mechanism of renal toxicity by CYP is penetration of fluids in lymphocytes and narrowing of blood vessels. (Qaiser, Maqbool & Jehanzeb, 2007)
Quercetin(3,3′,4′,5,7-pentahyroxyflavone) belongs to polyphenol flavonoids. The word flavonoid derived from “flavus” it represents that colour of compound is yellow. Quercetin is derived from “quercetum” meaning oak forest. It is lipophilic in nature so favours organic solvents as compare to inorganic or water.(Alexander.V et al., 2016) Most abundantly quercetin is present in onions.(Prakash et al.,2012) Quercetin is versatile in its action along with others most crucial action of quercetin is antioxidant effect. By blocking action of many enzymes quercetin depletes the formation of reactive oxidative species (ROS). Conclusively protect different organs from damage due to these free radical species. (Abhijit.S et al., 2016) Pesticides is broad term that includes all the pest control substances. The agents that have inhibitory activity against insects, rodents, fungi, harmful herbs and molluscs species are all classified under the pesticides.(Jyostana et al., 2009)
Quercetin plays important role in the erythrocyte damage due to cigarette tar that produces free radicals. Reactive species of free radicals are cause many problems like apoptosis and cancer. By blocking the enzymes like COX (Cyclooxygenase) and lipoxygenase that are said to be inflammatory enzymes quercetin gives anti-inflammatory effect. On the other hand it also inhibits the aggregation of fat in cells and induce apoptosis in pre-existing fat. This effect make it useful for the obesity. Quercetin also have remarkable pharmacological effects related to cancer, osteoporosis, ulcer, allergies and cardiovascular system.(Alexander, Radhakrishnan, Subramani, 2016)
The study suggests that the problems with clinical use of quercetin are associated with the pharmacokinetic parameters. In contrast to pharmacological actions quercetin is less useful pharmaceutically. (Nasrin et al., 2018)
The issues related to pharmaceutical use of quercetin can be improved by the loading drug into nanoparticles. This microencapsulation of drug increases bioavailability and drug become stabilized.
The most attractive feature of nano-biotechnology is the target specific delivery of drug. Due to which chance of side effects may reduces.( S. NATHIYA et al., 2014)With the passage of time and advancements in study different methods has been developed for drug delivery. Many nano-sized formulation has also been prepared with different levels of biocompatibility and biodegradability. Different problems of phytochemicals has also been resolved. Nanotechnology has greatly influenced their use in prevention of diseases and promotion of heath.(S.Wang et al., 2013)
The nano-sized drug delivery systems for polyphenols are classified into six major subclasses that includes cyclodextrins, nano-spheres, nano-capsules, solid lipid nanoparticles, micelles and liposomes.
Their structures have little changes but purpose is same to increase the bioavailability and biocompatibility of the loaded drug.The nano-spheres and nano-capsules poses almost same properties. They both require outer shell and drug in incorporated into centre of nanoparticles. The loaded drug attaches to the shell or bound chemically to facilitate the target specific delivery of drug. The outer shell is made up of polymer. Chitosan, PGA (Poly glycolic acid), PLGA (Poly-lactic-co-glycolic acid), PLA (Poly lactic acid), PCL (Poly ?-caprolactone), PEG (Polyethylene glycol) are most widely used polymers that provides biodegradable and biocompatible matrix to carry the drug.(Conte.R et al., 2016)
The poor stability of the product including nanoparticles can be overcome by using appropriate polymer that is more compatible with the body.(Akbarzadeh et al. 2012)
Nanoparticles can be prepared by number of methods that are divided into three classes. These classes consists of subclasses like amphiphilic macromolecule cross-linking (heat cross linking and chemical cross linking), polymerization based methods (emulsion polymerization, dispersion polymerization, interfacial condensation polymerization) and polymer precipitation methods (solvent extraction or evaporation, solvent displacement/nano-precipitation) and salting out). For poorly soluble drugs most favourable and convenient method is solvent displacement. (Bhatia, 2016)
There are numerous advantages of nanoparticle based formulation in comparison to conventional dosage forms including loading of hydrophilic as well as lipophilic drugs at the same time or separately, maintenance of drug stability, safety from enzymatic activity, reduced number of administrations and less side effects.(Tefas et al., 2015)
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