The Executive Editor, Pakistan Journal of Scientific and Industrial Research Pakistan Counsil for Scientific and Industrial, Karachi, Pakistan. Dear Prof. Dr. Muhammad Yaqoob,, Herewith, I submit the manuscript by Qurbat Zahra, Ahmad Fraz, Almas Anwar and Mudassar Abbas for your consideration as a review paper in PJSIR. The paper describes about “An Overview for the Synthesis of Silver-Nanoparticles and Blended Materials for Enhanced Biomedical Applications”. The paper shows novelty as the synthesis, characteristics and incorporation of silvernanoparticles and blended materials. Multiple routes for the development of such materials are explored and expressed here. The article presents the findings of a research conducted by multiple authors that gave me motivation to further extend my efforts to write a manuscript in appropriate format. While reviewing the areas of interest of various research journals, I could find no better option than to submit review article for publication in the Pakistan Journal of Scientific and Industrial Research. Various routes for synthesis of silver nanoparticles and blended materials have been observed and rephrased to bring it into proper manuscript form. I hope you would consider the manuscript for publication in PJSIR. With best regards, Mudassar Abbas (PhD) Assistant Professor, School of Textile and Design, University of Management and Technology, C-II Johar Town Lahore 54770, Pakistan. An Overview for the Synthesis of Silver-Nanoparticles and Blended Materials for Enhanced Biomedical Applications Qurbat Zahraa, Ahmad Fraza, Almas Anwara and Mudassar Abbasa* a School of Textile and Design, University of Management and Technology, C-II, Johar Town, Lahore 54770, Pakistan. Tel: 0092-423-111-300-200; E-mails: mudassar.abbas@umt.edu.pk, mudassirabbas@yahhoo.com Abstract: The existing data provides an adequate amount of information about synthesis of silver-nanoparticles through various routes. The particles thus formed when incorporated into blended materials can be used in advanced applications, especially in medical devices, preventing the adhesion of microorganisms over them. Herein, the similar function of silver, either distributed over the material surfaces as a polished layer or equally dispersed in the polymeric material, will be presented. Keywords: Antimicrobial properties, Blended materials, Green synthesis, Silver nanoparticles Introduction The Silver is one of the important coinage metals in group 11 of periodic table and is already known since ancient times due to its remarkable applications in making tools, utensils, aesthetically designed ornaments, and for medicinal applications [1]. Recently, the demanded application of silver has significantly increased when gigantic metal composites are broken down into small ultra-refined nanoparticles. The scope of this metal in the form of nanomaterials has been expanded in both academic and in industry, especially for chemiluminescent materials, micro-chips and biocidic applications [2]. In the later case, this application is important, when even tiny amounts of silver in materials make them practically useful against adhesion of micro organisms like virus, bacteria and fungi over them [3]. Besides, antimicrobial activity, high stability of silver nanoparticles at ambient temperatures and low volatility make them practically more applicable than any other material. The coating on polymers can be accomplished in both forms either only at polymer surfaces or real impregnation of silver into whole material [4]. The impregnation method is preferable due to more reliability and durability of material for long lasting protection of inner and outer core of the materials while Ag-polished materials gets chances of being deactivated by protein anions [5]. The amount of silver is also important in the manufacturing process of such materials as toxic applications due to excess amount of silver and less cleaning action due to insufficient quantity of silver lie at two different ends in the scale. For Example, the concentrations more than 5 ug/mL of silver in nano- form has been reported effective against necrosis or apoptosis of mouse spermetogonial stem cells [6]. Similarly, while studying antimicrobial charecteristics of 1w% silver nanoparticles incorporated in nylon 6.6, insufficient antimicrobial activities were examined [7]. Thereby, the amount of silver in either form is important for incorporation in the materials. Besides, the addition of transition metals to the environment has also been counted for major cause of contaminations for the systems accommodating living creatures and the contribution of silver is lesser as compared to other hazardous metals [8]. Accounting all these endeavors, the use of silver in all forms has significantly increased and it is becoming more demanding material with the passage of time. Keeping the same in view, a mini review is presented covering the major areas of different routes for silver nanoparticles, their impregnation in different polymer composites and fibers and finally the biomedical application including antimicrobial activity and toxic applications is presented. Scheme 1. The general reaction scheme for the synthesis of silver nanoparticles Syntheses of silver-nanoparticles The nanoparticles of silver in the range of 1-100 nm are generally synthesized by treating silver salt with capping agents and reducing agents after solubilizing in an optimal solvent. In a synthesis step, these factors combined with respective concentrations and followed experimental procedures define the size distribution and 3Dorientation of nanoparticles [9]. Due to low price, ease of availability and high chemical stability AgNO 3 is the most commonly applied metal salt. Both, sodium borohydride and sodium citrate separately applied in different experiments contribute one third among all the reducing agents reported in literature [10]. Besides, common laboratory chemicals like carbohydrates, acids, amines, bio-based substrates like organisms and special treatment methods like irradiation of reaction mixture has also been applied [11]. As solubilizers, many organic and inorganic solvents has been reported for nanoparticles formation but according to different data available, more than 80% of the syntheses have been accomplished in water as a solvent [12]. Organic solvents like ethanol, dimetylformamide, ethylene glycol and amines are among other commonly applied solvents [13]. The capping agents, also named as stabilizing agents are generally added to prevent aggregation of the nanoparticles after the formation. Polymer based composites are useful precursor employed for the same purpose. Poly(vinylpyrrolidone) (PVP) is second most abundantly applied polymer after sodium citrate (27%) for such purposes [14]. Similarly, poly(nisopropylacrylamide) (PNIPAM) is used as reducing agent when nanaoparticles of demanded low critical solution temperature applications are required [15]. The arbitrary literature available for demanded application provides a wide range of data for nanoparticles syntheses for both general and specific applications but a greener route for synthesis where least number of chemicals applied in ideally no solvent and within shorter durations of time, were still demanded. Counting the same factors, the solvent free synthesis of oleylamine capped silver nanoparticles were established in our laboratory. Oleylamine was used as both solubilizing and stabilizing agent and heating ten folds excess of it with AgNO3 at 165oC for thirty minutes, black precipitates of silver nanoparticles were obtained. After precipitation and washing three times in ethanol, the nanoparticles were characterized to study the UV-absorbance, size measurements and stability of volatile ligands attached after dissolving in chloroform [16]. The particles synthesized through this method were also readily soluble in many organic solvents like toluene, dichloromethane and diethylether. Various route selected for syntheses of silver nanoparticle are reported in Table 1. Figure1. Table 1 Materials equipped with silver for antimicrobial applications The strong antimicrobial activity of materials containing silver is followed either with the release of silver ion or silver nanoparticles in the solution to behave strongly against micro organisms [40]. The detailed mechanism is still unknown but different assumptions are available for silver ions and nanoparticles for their activity against micro organisms. For example, according to many authors silver ion binds strongly to the nitrogen, sulphur and oxygen in different proteins and causes the killing of cell wall of bacteria and hence reducing the cell count [5]. Similarly, in an activity, the cell functions like permeability and respiration are also disturbed when silver ion makes complexes with proteins and DNA [41]. Such activity has been observed in Ag-zeolites complexes which behave as strong antimicrobial agent. The slow dissociation of silver ion in saliva of mouth is helpful in reducing the plaque in dental application with least harm to the human health [42]. Different counts of 2.5-7.5 wt% of zinc silver zeolite have been reported for strongly antimicrobial and favorable for denture based resins but all concentrations above 2.5wt% showed significant change in mechanical properties of the material [43]. In past, three different techniques have been applied for nanocomposite formation: first one includes the spreading of silver nanoparticles over the polymer matrix, in second process in-situ preparation of silver nanoparticles by electronically active polymers used as both reducing agents and entrapping agents is established, and in third nanoparticles are mixed with the monomer before polymerization process. In the last described technique, nanoparticles are ideally equally distributed among the whole core of the polymer matrix and show more efficiency than the other methods [5]. In some cases, materials releasing silver nanoparticles produce stronger effects against bacterial activity than silver ion releasers. For example, in comparison of silver nano based poly(methylmethacrylate) (PMMA) and sulphadiazine / AgNO 3, the former showed stronger kill rates for E. coli and S. aureus bacteria by releasing the silver nanoparticles of 7 nm range [44]. Additionally, no black precipitates were formed in the later case whereas, this phenomenon is commonly observed in experiments releasing Ag-ions. Figure2. Similar studies has also been evaluated for block copolymers, e.g. poly(urethane)/poly(ethylene glycol) and TiO2 based polymers when attached with silver yielded material of high activity against E.coli and S.auserus bacteria [45]. In another example, poly(vinyl alcohol)/ poly(methylmetacrylate) based polymers and several other polymers have been reported for advanced applications [44]. Recently, poly(dicyclopentadiene) an advanced duroplastic material with high mechanical strength, low cost and ease of formation emerged [46]. A way to create poly(dicyclopentadiene) bearing antimicrobial properties was recently established [16]. Polymerization of dicyclopentadiene via ring opening metathesis polymerization in presence of 1w% of silver nanoparticles yielded an antimicrobially equipped thermosetting material, as exemplified by the complete killing of E.coli colonies (as determined according to the Japanese international standard Z2801:2000) [47]. Silver nanoparticles are also produced by electrochemical process. Aqueous solution of NaNO 3 was polarized in ethanol and a deposit of metallic silver nano particles was obtained [48]. In an example when silver filmsand solution of physiological saline were immersed together the dissolution of Ag2O occurs and formation of Silver causes the inhibition of growth of E. coli and S. aurses and P. aruginosa [49] When PVC is modified with NaOH and AgNO 3 it inhibits the production of P.aeruginosa calonies in endotreacheal tubes. [50] Similarly, in situ process for fine collidal silver had been done. In this poly (ethylene glycil dimethylacrylate) was used with control surface area and surface functionality. This materail showed high antimicrobial activity for different bacterial strains [50] Conclusion As the conclusion of the article, the basic information about the synthesis of silver nanoparticles, incorporated materials and activity of such materials against microorganisms is presented. The multiple routes for the syntheses of silver -nanoparticle include silver nitrate and water as the major components for silver salt-resource and as a solvent respectively. For reducing agents; sodium borohydride, natural extracts, reducing sugars and electromagnetic radiations are utilized, whereas for the capping agents; polymers, carbohydrates, long chain fatty acids and natural extracts are used. The analysis of different products developed through incorporation of silver-nanoparticles clearly depicts that material contain property of disinfecting microbes. 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Han, etal, "Synthesis of Metal/Polymer Colloidal Composites by the Tailored Deposition of Silver onto Porous Polyme rMicrospheres," Journal of Polymer Science: Part A: Polymer Chemistry, vol. 42, pp. 2551-2557, 2004. Scheme 1. The general reaction scheme for the synthesis of silver nanoparticles Table 1. Selected Model for the Syntheses of Silver- Nanoparticles from Silver Nitrate. Size Reducing-Agent Solvent Capping Agent Reference (nm) Polyvinyl alcohol Variable [17] Trisodium Citrate 4.4 -5 [18] Sodium borohydride 12 [19] Oleic acid 8 [20] <3 [21] Variable [22] 7 [23] 5-8 [24] 50 [25] 10 [26] 30.5 [27] Variable [28] 3-14 [29] 6.1 [30] 15 [31] (PVA) Water Polyvinyl pyrolidone Sodium (PVP), Trisodium borohydride Citrate Water/ Chloroform Hexadecyl amine Trisodium Citrate + Ethanol/Toluene Dodecylamine PolyEthanol Methylmethacrylate( PMMA) Bacterium Bacillus Bacterium Bacillus licheniformis licheniformis Capsicum annuum Capsicum annuum L. L. extract extract Spent mushroom Spent mushroom substrate substrate Fructose, Glucose, Water Fructose, Glucose, Sucrose Sucrose Vitamin E N.A Vitamin B2 Vitamin B2 (Riboflavin) (Riboflavin) Sodium Sodium carboxymethyl carboxymethyl cellulose cellulose Dodecylamin& Dodecylamine & Water/ Cyclohexane Formaldehyd 4 [32] 4.7 [33] Formaldehyde Cetyltrimethylammo Octadecylamine Octadecylamine nium bromide Ethylene glycol Ethylene glycol Polvinyl pyrolidone Variable [34] Oleylamine Oleylamine Oleylamine 63 [16] Ascorbic acid Water 35 [35] Cetyltrimethylammo nium bromide H2 Gas Water/Toluene PVP/PVA/ Starch Variable [36] ã- irradiationa Water PVP Variable [37] Ethylene Glycol PVP Variable [38] Water Fluff pulp N.A [39] Microwave irradiationc Sonochemical irradiationa Irradiation was not used for reducing medium but it provides assistance for free electron or reduction. Ag-salt Reducing agents Solvent Capping agents 100 90 80 70 Abundance (%) a 60 50 40 30 20 10 0 AgNO3 Citrate / PVP H2O NaBH4 / citrate Chemicals Fig. 1a: Most frequently employed chemicals for synthesis of Ag-nanoparticles [16] Fig. 1b: An exemplary UV-visible spectrograph for silver nanoparticlces [16] Figure2. Specimen example for ROMP of DCPD in presence of 1w% oleylamine stabilized silver nanoparticles