| BackgroundAlong with gold,another rare and precious metal,silver has been widely utilized for thousands of years in human history,applications including jewellery, utensils, monetary currency, dentalalloy, photography or explosives. Among silver's many applications, those exploiting its disinfectant property for hygienic and medicinal purposes are time honoured and prominent,though the mechanism is not yet fully understood.From ancient times, metallic sliver has been known as a safety anti-bactericidal material with broad spectrum. In 20th century, silver sulfadiazine was widely used to treat burns and scalds and to prevent the proliferation of Pseudomonas aeruginosa and is still uesd in burn units. Silver nitrate aqueous solution was used for anti-inflammatory in Ophthalmology. And sliver-mercury alloy was used as Dental materials.Irreversible pigmentation of the skin and/or the eye,i.e. argyria or argyrosis, due to silver deposition,may develop after prolonged exposure to silver or silver compounds. Due to this problem and together with the advent of antibiotics like penicillins and cephalosporins,silver's luster largely faded away as an anti-infection agent.However,advancement of modern science has helped silver renew its lost luster.Metallic silver is subjected to new engineering technologies with resultant extraordinarily novel morphologies and characteristics. Instead of being made "big", metallic silver is engineered into ultrafine particles whose size is measured in nanometres(nm).When these particles have at least one dimension,which is less than 100nm,they are named nanoparticles. Upon reaching nanoscale, like other nanomaterials and primarily by virtue of extremely small size,silver particles exhibit Remarkably unusual physicochemical properties and biological activities. As a consequence, applications of engineered silver nanoparticles (nanosilver) especially in the health care sector have been and are being heatedly explored. In medical arena,there are wound dressings,contraceptive devices, surgical instruments and bone prostheses all coated or embedded with nanosilver.It is estimated that of all the nanomaterials in medical and health care sector, nanosilver application has the highest degree of commercialization. Therefore, exposure to nanosilver in the body is becoming increasingly wide spread and intimate.With the continuous development and application of nanosilver, people are more vulnerable to expose in nanosilver in daliy life. And therefore, silver nanoparticles are more easier to get into the body and to interact with tissues, cells and biological molecules.Especially in the medical field, compared with other nano-materials, nanosilver products can be directly applied to the human body and can be contacted with blood, body fluid or the lymphatic system. The traditional belief is that except for argyria or argyrosis and some minor problems, silver is relatively non-toxic to mammalian cells. Silver poisoning only occurs among workers who have chronic history of silver exposure. Drake and Hazelwood have reviewed health effects of silver and silver compounds from aperspective of occupational exposure. Metallic silver was viewed to be a minimal health risk.However,once reaching nanoscale, certain materials do exhibit significant toxicity to mammalian cells even if they are biochemically inert and biocompatible in bulk size,e.g.carbon.When it comes back to silver nanoparticles, in sharp contrast to the attention paid to their applications, only a few studies have provided very limited insights into such aspects as their entry portals into human body, absorption, biodistribution, organ accumulation, metabolism, excretion as well as their potential interactions with tissues, cells and molecules and their relevant toxicological implications. It is our opinion that these are questions that need to be imperatively answered before people rush to indulge into the nano silver boom.The aim of this paper is to make a deeper study of the absorption and biodistribution of nanosliver in the organs of rabbits such as blood, liver, kidney and spleen and to evaluate the biological safety of silver nanoparticle dressings, so as to provide a theoretical basis for the clinical application of nano-silver dressings.Chapter 1 Research on Nano Sliver Distribution In Vivo After The Application Of Agem(?) Silver Nanoparticle Dressings On TraumaObjectiveStudy the absorption and biodistribution of nanosliver in the organs of rabbits such as blood, liver, kidney and spleen after the abdominal wounds of rabbit ears treated with silver nanoparticle dressings so as to evaluate the biological safety of silver nanoparticle dressings and provide a theoretical basis for the clinical application of nano-silver dressings. Materials and methods1.Fifty-four healthy adult New Zealand rabbits which weight between 2.5 kg and 3.5 kg were randomly divided into three groups with 18 rabbits in each group.One of the three group was normal control group without any interference (group A). The other two groups were tested with nanosliver dressings, which were dressings for single time group(group B) and dressings for multiple times group(group C).Both B group and C group were divided respectively into six small groups with three rabbits per group. Full-thickness excisional wounds,10 mm in diameter, were created over the ventral surface of rabbits' ears. Rabbits in A group were with no treatment, in B group were treated with silver nanoparticle dressings for single time and in C group were treated with dressings for multiple times. Dressings in six groups of C group were changed respectively in 0 day,2nd,2nd and 4th,2nd and 4th,2nd and 4th,2nd and 4th post treatment days(PTD) after injury. And dressings were all removed in 7th post treatment days in both group B and group C.2. Blood(15ml), liver, kidney and spleen were respectively collected from the rabbits of group A,B and C to determine the silver contents in 2nd,4th, 7th,14th,30th,60th after injury.3. Statistics methods:Data were denoted as x±s and analyzed with SPSS13.0 software. Statistical significance of differences was determined by analysis of variance of factorial design and P<0.05 was regarded as statistical significance.Results1. The sliver contents in blood, liver, kidney and spleen of group B and C were significantly higher than those of group A (P<0.05) in 2nd PTD.2. In 4th PTD, the sliver contents in blood, liver, kidney and spleen of group B and C were still significantly higher than those of group A (P<0.05). However, the silver contents in four organs of group C showed a progressive increase with time trend while those of group C showed a progressive decrease with time trend. And in 7th PTD, the sliver contents in blood, liver, kidney and spleen of group C were significantly higher than those of group B (P<0.05)3. After removing the nanosilver dressings, compared with the previous time point, the silver contents of group B and C declined rapidly. And there is statistical significance of difference in group C(P<0.05).4. In 30th and 60th PTD, there were no significant differences of the sliver contents among three groups(P>0.05).ConclusionAfter the application of Agem(?) silver nanoparticle dressings on trauma, it is rapidly absorbed through skin wounds into the circulatory system and then deposited into the liver, kidney and spleen. While removing the dressings,the sliver contents in blood, liver, kidney and spleen declined rapidly to the normal value. It was proved to be safe to have the silver nanoparticle dressing applied on trauma.Part Two:Research On The Toxicological Safety Of Nano Sliver After The Application Of Agem(?) Silver Nanoparticle Dressings On TraumaObjectiveStudy the impact which nanosliver makes on the the physiological and biochemical index of blood to evaluate the toxicological safety of silver nanoparticle dressings. Materials and methodsEach rabbit was to fast for 12h before we got its organs. And we collected its blood when the rabbit is awake and can be free to drink water. lmL blood sample was collected for measuring the physiological index of blood and 3 mL blood sample was for measuring the biochemical index of blood.We measured three physiological indexs which was RBC,WBC and Hemoglobin in the help of animal blood cell analyzer of HEMAVET950. And We measured three biochemical indexs which was Urea nitrogen,Creatinine and ALT in the help of automatic biochemical analyzer of Sysmex Chemix-180.Statistics methodsSPSS13.0 soft ware was employed for statistical analysis. Data were denoted as x±s. Significant differences were determined by one-way-ANOVA and and P<0.05 was regarded as statistical significance.Results1. Physiological index:There was no significantly difference of RBC,WBC and Hemoglobin in three groups at each of six different times.(P>0.05)2. Biochemical index:There was no significantly difference of Urea nitrogen,Creatinine and ALT in three groups at each of six different times. (P>0.05)ConclusionIn the condition of this experiment, Agem(?) nanosilver has ideal toxicological safety and has no obvious toxic effect on the body. |
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