Research Article Lambda-Cyhalothrin Nanosuspension Prepared by the Melt Emulsification-High Pressure Homogenization Method

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1 Journl of Nnomterils Volume 215, Artile ID , 8 pges Reserh Artile Lmd-Cyhlothrin Nnosuspension Prepred y the Melt Emulsifition-High Pressure Homogeniztion Method Zhenzhong Pn, 1,2 Bo Cui, 1 Zhnghu Zeng, 1 Lei Feng, 1 Guoqing Liu, 1 Hixin Cui, 1 nd Hongyu Pn 2 1 Institute of Environment nd Sustinle Development in Agriulture, Chinese Ademy of Agriulturl Sienes, Beijing 181, Chin 2 College of Nturl Resoures nd Environment, College of Plnt Siene, Jilin University, Chnghun 1362, Chin Correspondene should e ddressed to Hixin Cui; hixinui@s.n nd Hongyu Pn; pnhongyu@jlu.edu.n Reeived 22 April 215; Revised 3 July 215; Aepted 8 July 215 Ademi Editor: Jin-Ho Choy Copyright 215 Zhenzhong Pn et l. This is n open ess rtile distriuted under the Cretive Commons Attriution Liense, whih permits unrestrited use, distriution, nd reprodution in ny medium, provided the originl work is properly ited. The nnosuspension of 5% lmd-yhlothrin with.2% surftnts ws prepred y the melt emulsifition-high pressure homogeniztion method. The surftnts omposition, ontent, nd homogeniztion proess were optimized. The nioni surftnt (1-dodenesulfoni id sodium slt) nd polymeri surftnt (mlei rosin-polyoxypropylene-polyoxyethylene ether sulfonte) sreened from 12 types of ommerilly ommon-used surftnts were used to prepre lmd-yhlothrin nnosuspension with high dispersity nd stility. The men prtile size nd polydispersity index of the nnosuspension were 16.1 ±.11 nm nd.266 ±.2, respetively. The high zet potentil vlue of 41.7 ± 1.3 mv nd stle rystlline stte of the nnoprtiles indited the exellent physil nd hemil stility. The method ould e widely used for prepring nnosuspension of vrious pestiides with melting points elow oiling point of wter. This formultion my void the use of orgni solvents nd redue surftnts nd is perspetive for improving iovilility nd reduing residul pollution of pestiide in griulturl produts nd environment. 1. Introdution Pestiides hve een widely pplied in integrted pest mngement of rop prodution. However, most of effetive pestiide ompounds hve poor wter soluility, whih limits the further development of wter-sed formultions [1, 2]. There re some prolems on onventionl pestiide formultions suh s emulsifile onentrte (EC), wettle powders (WP), nd miroemulsion (ME), inluding the use of orgni solvent, drift, nd rinfstness, whih used low effiy nd severely environmentl ontmintion [3]. Nnosuspension hs een onsidered to e n importnt nd promising ndidte to overome the prolems mentioned ove due to thesignifintinreseonqueousdispersityndsoluility of nnoprtile s desried y Ostwld-Freundlih eqution [4 7]. Pestiide nnosuspension is nnoolloidl dispersion of pestiide tive ompound prtiles in rystl or morphous stte stilized y surftnts[8, 9]. Nnosuspension not only ould solve the prolem of poor soluility ut lso ould improve permeility, iotivity, nd effiy of pestiide [1]. Generlly, nnosuspension in phrmeutil field n e produed either y top-down pprohes, suh s medi milling, high pressure homogeniztion (HPH), melt emulsifition method, nd high pressure mirofluidiztion, or ottom-up tehniques, suh s preipittion nd superritil fluid method [11 13]. Reently, the omintion of the melt emulsifition nd HPH method (melt emulsifition-hph method) [14] hs ttrted intense ttentions, owing to voiding use of orgni solvents nd reduing the energy onsumption of milling during the prodution proess. However, the relted reserh in pestiide formultions ws hrdly reported. The si proesses of the melt emulsifition- HPH method re desried s follows. The pestiide ws melted in wter t temperture ove the melting point nd emulsified in high pressure homogenizer. The effetiveness of HPH is relted to the hrdness of the drug prtile, the homogeniztion pressure, nd the numer of yles [15 18].

2 2 Journl of Nnomterils F 3 C Cl O H 3 C CH 3 O CN Figure 1: Chemil struture of lmd-yhlothrin. As shown in Figure 1, lmd-yhlothrinisverypoor wter solule syntheti pyrethroid insetiide (5 1 6 g/l t 25 C) nd highly effetive ginst wide rnge of pests [19]. The urrent formultions of lmd-yhlothrin inlude WP, EC, ME, nd emulsion in wter (EW) [2, 21]. In this study, we prepred lmd-yhlothrin nnosuspension y the melt emulsifition-hph method with the omintion of nioni nd polymeri surftnts. The prtile size nd distriution of the nnosuspension were investigted y dynmi light sttering (DLS). The morphology nd stility of prtile were hrterized y snning eletron mirosopy (SEM), X-ry diffrtion (XRD), nd high performne liquid hromtogrphy (HPLC). 2. Experimentl Methods 2.1. Mterils. Lmd-yhlothrin (96%) ws purhsed from Yngnong Chemil Co., Ltd. Polyroxylte nd mlei rosin-polyoxypropylene-polyoxyethylene ether sulfonte (MRES) were provided y Jingsu Sinvohem S&D., Ltd. 1-Dodenesulfoni id sodium slt (SDS), sodium luryl ether sulfte (SLES), polyvinylpyrrolidone K3 (PVP K3), polyvinylpyrrolidone K9 (PVP K9), sodium lignin sulfonte (SL), nd polyoxyethylene soritn monoolete (Tween 8) were purhsed from J&K Chemil. Polyethylene glyol mono-4-nonylphenyl ether (PEGNPE) ws purhsed from Alf Aesr. Hydroxypropyl methyl ellulose (HPMC), poloxmer 188 (F68), soritn olete (Spn 8), nd mnnitol were otined from Sigm-Aldrih. HPLC grde methnol ws purhsed from Fisher. The wter used in ll nlytil experiments ws Milli-Q wter (18.2 MΩ m, TOC 4pp) Methods The Preprtion of Lmd-Cyhlothrin Nnosuspension. Lmd-yhlothrin nnosuspension ws produed y the melt emulsifition-hph method. Lmd-yhlothrin powder ws dispersed in deionized wter ontining surftnts t 8 C (ove the melting point of lmdyhlothrin) nd emulsified with C25 shering mhine (ATS,Germny)t1,rpmfor2min.Susequently,the emulsified mixture ws homogenized using AH1D high pressure homogenizer (ATS Engineer In., Cnd) under different pressures in the rnge of 2 1 r for 15 yles. Finlly, the nnosuspension ws otined y ooling down the homogenized mixture to room temperture in order to solidify the melted droplets into nnoprtiles. The totl proedures of the flow were shown in Figure 2. O Prtile Size nd Zet Potentil of the Nnosuspension. The men prtile size, 9% of the prtile volume elow ertin size (D9), polydispersity index (), nd zet potentil of the nnosuspension were mesured y DLS with Zetsizer Nno ZS9 (Mlvern Instruments, UK) t 25 C t sttering ngle of 9. The mesurement of eh smple ws rried out in triplite for reliility Morphology Chrteriztion of Nnoprtiles. The morphology of lmd-yhlothrin nnoprtiles ws investigted y JSM-741F snning eletron mirosopy (SEM) (JEOL, Jpn) with n elerting voltge of 3 kv. The smples were dropped on silion slie, dried nturlly, nd oted with thin lyer of pltinum for 3 s using ETD-8 sputter oter (Beijing Elorte Tehnology Development Ltd., Chin) Crystlline Stte Anlysis of Nnoprtiles. The solid powder of lmd-yhlothrin nnoprtiles ws prepred from the nnosuspension y freeze drying using FD-81 freeze dryer (EYELA, Jpn) for 24 h t.4 P. The rystlline stte ws hrterized y D8 Advne X-ry diffrtometer (Bruker AXS In., Germny) with Cu Kα rdition generted t 4 kv nd 4 ma urrent. Smples were nlyzed in 2θ rnge of 8 55,withstepsizeof.2 nd time step of.1 s Stility Mesurement. The suspensiility test ws onduted ording to GB/T , Chin [22]. 5. g lmd-yhlothrin nnosuspension ws diluted in 25 ml stndrd hrd wter t 3 C. The diluted nnosuspension ws pled under 3 C wter th for 3 min. Then the top 225 ml of the solution ws removed. The drug ontents of the originl suspension nd the left 25 ml solution were mesured y HPLC. The suspensiility (w)ws lulted y the following eqution: w (%) = m 1 m 2 1 1, (1) m 1 9 where m 1 nd m 2 re the pestiide ontent of originl suspension nd the left 25 ml solution t the ottom, respetively. The unit for m 1 nd m 2 is grm (g). The storge stility ws tested ording to HG/T ,Chin [23]. The nnosuspension ws stored in losed glss vil t Cfor7dysnd54 Cfor14dys.After storge, smples were drwn to ssess physil nd hemil stility. Chemil stility ws tested y nlyzing lmdyhlothrin remining of the nnosuspension with HPLC HPLC Anlysis. Lmd-yhlothrin ontent ws nlyzedyhplc(wtersalline2695)troomtemperture using WATO4595 C18 nlytil olumn nd 278 nm UV detetor. The moile phse ws mixture of methnol nd wter (8 : 2, v/v) nd the flow rte ws 1. ml/min Sttistil Anlysis. All mesurements were onduted in triplite. The dt were reorded s men ± stndrd devition nd nlyzed y one-wy nlysis of vrine

3 Journl of Nnomterils 3 Lmd-yhlothrin powders 8 C Shering HPH Cooling down 1 2 Cvittion Shering 3 Figure 2: Shemti representtion of lmd-yhlothrin nnosuspension preprtion. (1) Surftnt queous dispersion. (2) The emulsifiedmixture. (3) Lmd-yhlothrin nnosuspension. Tle 1: The influene of surftnt on the men prtile size nd of lmd-yhlothrin nnosuspension. Surftnt Men prtile size (nm) SL ± 2.4e.137 ±.6 SDS ±.4h.389 ±.9 F ± 2.5e.231 ±.23 SLES ± 1.86e.169 ±.16 MRES ± 1.2fg.233 ±.24 HPMC ± ±.398 PEGNPE ± 2.25g.172 ±.28 Tween ± 3.24f.22 ±.5 Spn ± 5.73d.238 ±.28 PVP K ± ±.14 PVP K ± ±.52 Polyroxylte ± 1.8d.139 ±.26 Different letters t eh dt indite signifint differenes ording to Dunn s multiple rnge test t P <.5. (ANOVA) nd Dunn s multiple rnge test. Signifine ws tested t the.5 level of proility. Sttistil nlysis ws performed with the softwre pkge SPSS. 3. Results nd Disussion 3.1. The Influene of Surftnts on the Prtile Size nd Dispersity of Lmd-Cyhlothrin Nnosuspension. When the surftnt ontent ws less thn hlf the tive pestiide ingredient, rpid deposition phenomenon ws oserved in most suspensions stilized y single surftnt, so the 2 : 1 rtio of lmd-yhlothrin to surftnt ws determined to sreen the optiml surftnts for lmd-yhlothrin nnosuspension. The nnosuspension ontining 1% (w/w) lmd-yhlothrin nd.5% surftnt (w/w)wsprepred y the melt emulsifition-hph method. The sttistil result reveled tht surftnt hd signifint impt on the prtile size nd dispersity of the nnosuspension (P <.5). As shown in Tle 1, mong twelve surftnts, four surftnts (SDS,MRES,Tween8,ndPEGNPE)reduedthemen prtile size of the nnosuspension less thn 2 nm; in prtiulr the SDS redued men prtile size to s low s ±.4 nm. As nioni surftnt, SDS n keep the Tle 2: The influene of omplex surftnts on the prtile size nd dispersity of the nnosuspension. Formultion Men prtile size (nm) D9 NS ± ± ± 11. NS ± ± ± 27. NS ± ± ± 7.77 Note: NS-1: SDS + MRES (1 : 3, w/w), NS-2: SDS + PEGNPE (1 : 3, w/w), nd NS-3: SDS + Tween 8 (1 : 3, w/w). Different letters t eh dt indite signifint differenes ording to Dunn s multiple rnge test t P <.5. pestiide prtiles well dispersed vi eletrostti repulsion [24]. MRES is nioni polymer whih n fford eletrostti repulsion nd sustntilly steri rrier t the interfe of individul prtile [25]. Nonioni surftnts, PEGNPE nd Tween 8, ould inhiit ggregtion of prtiles y dsoring onto the nnoprtiles through the hydrophoi setion. It seems tht intertions etween hydrophoi res of lmd-yhlothrin, PEGNPE, nd Tween 8 were sustntil for nnoprtiles [26]. Therefore, SDS, PEGNPE, Tween 8, nd MRES were hosen for further optimiztion. Although SDS deresed signifintly the prtile size of the nnosuspension, the high vlue indited the poor dispersity in wter. Bsed on the result of surftnt sreening, the omplex effet of surftnts ws onsidered nd further investigted. It hs een reported tht the omintion of nioni surftnt nd nonioni surftnt ould offer eletrostti nd steri repulsion for the nnosuspension stiliztion [27, 28]. Therefore, the omplex effet of SDS with PEGNPE, Tween 8, nd MRES ws investigted on theprtilesizenddispersityofthennosuspensionwith 5% (w/w) lmd-yhlothrin nd.2% (w/w) surftnts. Tle 2 presented the mesuring results of the prtile size nd dispersity of three nnosuspension formultions with omplex surftnts, NS-1 (ontining SDS nd MRES), NS- 2 (ontining SDS nd PEGNPE), nd NS-3 (ontining SDS nd Tween 8). Among the three formultions, smllest prtile size nd nrrow distriution were oserved with the omplex surftnts of SDS nd MRES (1 : 3, w/w) in NS-1, whih ws signifintly smller thn those of the other two nnosuspensions (P <.5). Thus, SDS nd MRES (1 : 3, w/w)werehosenstheoptimlomplexsurftnts.

4 4 Journl of Nnomterils Prtile size (nm) d d Surftnts onentrtion (%) d d Surftnts onentrtion (%) Men prtile size D9 () () Figure 3: Effet of surftnts onentrtion on () prtile size nd () of the nnosuspension. Different letters t eh dt indite signifint differenes ording to Dunn s multiple rnge test t P <.5. Prtile size (nm) d d Homogeniztion pressure (r) Homogeniztion pressure (r) Men prtile size D9 () () Figure 4: Effet of homogeniztion pressure on () prtile size nd () of the nnosuspension. Different letters t eh dt indite signifint differenes ording to Dunn s multiple rnge test t P < Optimiztion of the Surftnts Conentrtion. As shown in Figure 3, men prtile size nd D9 of lmd-yhlothrin nnosuspension were redued long with inrese on the onentrtion of surftnts from.1% to.2% (w/w) nd inresed signifintly from.2% to 7.5% (w/w) (P <.5). Presumly, t low onentrtion, the surftnt redued the interfil tension nd prevented drug prtiles from ggregting; when oth omplex surftnts onentrtion rehed ritil mielle onentrtion (CMC MRES =1.3g/L nd CMC SDS =2.45g/Lt25 C), the drug prtiles were wrppedinthemielles,givingrisetoinreseonprtile size. Additionlly, exhiited similr trend to prtile size, while the surftnts onentrtion hnged from.2% to 7.5% (w/w). Therefore,.2% (w/w), proper onentrtion of surftnt, ws hosen for the preprtion of lmdyhlothrin nnosuspension Optimiztion of the Homogeniztion Condition. Generlly, the homogeniztion pressure is the key prmeter of HPH proess to determine the prtile size of the nnosuspension [29]ndtheeffethseenprovedinthisinvestigtion (P <.5).Thus,theyleswerefixedt15forehpressure nd the vrious HPH pressures were investigted in detil. As shown in Figure 4, themenprtilesize,d9,nd deresed s pressure inresed from 2 to 8 r. At 8 r,themenprtilesizendd9were16.1±.11 nm nd 54. ± 11. nm t 8 r, respetively. When the pressure ws ove 8 r, D9 nd signifintly inresed long with slight inrese on men prtile size. It seemed tht ontinuous inrese on pressure ould not fford redution of prtile size. Therefore, the optiml formultion ws the ft tht 5% (w/w) lmd-yhlothrin nnosuspension with.2% surftnts (w/w)of SDS nd MRES(1:3,w/w)ws prepred y the melt emulsifition-hph method of 8 r with 15 yles Morphology of the Nnosuspension. The prtiles of lmd-yhlothrin nnosuspension presented sphere-like shpe s oserved in SEM imging (Figure 5()). The sttistil men prtile size sed on 1 prtiles from SEM imging ws 57.7 nm (Figure 5()), whih ws well in

5 Journl of Nnomterils Numer of prtiles () Size (nm) () Intensity (%) Size (nm) () Figure 5: () SEM imging, () sttistil prtile size sed on SEM imge (1 prtiles), nd () hydrodynmi prtile size distriution of lmd-yhlothrin nnosuspension mesured y DLS. greement with the D9 mesured y DLS (Figure 5()). This ould e ttriuted to the sher nd vittion effet, disintegrting lrge prtiles into nnosized prtiles during the HPH proess [3] Chrteriztion of Crystlline Stte. It is well known tht the rystlline stte of nnoprtiles signifintly influenes the soluility, stility, nd iovilility of nnosuspension formultions [31]. High pressure dopted in this proess my hnge the rystlline stte of lmd-yhlothrin [32]. Therefore, the effet on the rystlline stte ws exploited with freeze-drying method whih hs good ility to preserve the originl struture of mterils omined with surftntsduringdrying [33, 34].Figure 6 showed the X-ry powder diffrtogrm profiles of MRES, SDS, mnnitol, nd lmd-yhlothrin, physil mixture of them, nd lmdyhlothrin nnoprtiles. The typil diffrtion peks of lmd-yhlothrin remined in the nnoprtiles fter the HPH nd freeze-drying, inditing the rystlline stte of the lmd-yhlothrin kept lmost unhnged. The rystlline stte of lmd-yhlothrin nnoprtiles is enefiil to long-term stility [31]. Menwhile, the rystllite size of lmd-yhlothrin nnoprtile ws lulted to e 57.3 nm with Sherrer s eqution, whih ws similr to the prtile size mesured y DLS nd SEM. This result reveled the good stility during solidifition nd dispersity of the pestiide nnoprtiles in solution Stility of Nnosuspension. As shown in Figure 7, the suspensiility of the nnosuspension ws 99.1 ±.3% initilly. After storge t Cfor7dysnd54 Cfor14dys,the suspensiilities of the nnosuspension were 98.2 ±.3% nd 97.7 ±.4%, respetively, inditing its high stility. In ddition, the zet potentil of lmd-yhlothrin nnosuspension remined 41.7 ± 1.3 mv owing to the oting ofsdsndmres.itiswellknownthtsolutevlue of zet potentil of pproximte 3 mv exhiits enough eletrostti repulsion etween the nnoprtiles to prohiit ggregtion [29]. Furthermore, the nioni polymer MRES on the surfe of prtile offers steri hindrne to enhne stility. As shown in Figure 8, the men prtile size of the nnosuspension ws 16.1 ±.11nm initilly nd silly

6 6 Journl of Nnomterils Nnoprtiles 1 Physil mixture Lmd-yhlothrin Mnnitol Prtile size (nm) SDS dy 7 dys t C 14 dys t 54 C MRES θ (deg) Figure 6: X-ry diffrtion ptterns of lmd-yhlothrin nd relted exipients Men prtile size D9 () Suspensiility (%) dy 7 dys t C 14 dys t 54 C Suspensiility.1 dy 7 dys t C 14 dys t 54 C () Figure 8: The hnges of () prtile size nd () of the nnosuspension under different storge onditions. Different letters t eh dt indite signifint differenes ording to Dunn s multiple rnge test t P <.5. Figure 7: The suspensiility of the nnosuspension under different storge onditions. Different letters t eh dt indite signifint differenes ording to Dunn s multiple rnge test t P <.5. remined unhnged fter storge t Cfor7dys.Menwhile, t 54 C for 14 dys, the men prtile size inresed to ±.65 nm, n inrese used y ggregtion of fewer prtiles. On the other hnd, of the nnosuspension deresed slightly, inditing exellent stility. These results suggested suffiient physil stility of lmd-yhlothrin nnosuspension for storge. In ddition, the lmd-yhlothrin onentrtion kept lmost onstnt t Cfor7dysnd54 Cfor14dys inditing tht the nnosuspension showed n exellent hemil stility (Figure 9). Presumly, the surrounding surftnts proteted lmd-yhlothrin moleules from degrdtion. As shown in Figure 1, there is no pprent differene in the XRD powder diffrtogrms, inditing tht the rystlline stte of lmd-yhlothrin nnoprtiles ws stle. Overll, the nnosuspension of lmd-yhlothrin prepred y the melt emulsifition-hph method presented exellent stility in physil nd hemil properties. 4. Conlusion In summry, the nnosuspension of 5% (w/w) lmdyhlothrin ontining.2% surftnts (w/w) ws prepred with high dispersity nd stility y the melt emulsifition- HPH method. It ws demonstrted tht the surftnts nd homogeniztion pressure hd signifint effets on prtile size nd dispersity of the nnosuspension. The nioni surftnt (SDS) nd polymeri surftnt (MRES) sreened from 12 types of ommon-used surftnts were determined to e optiml omplex surftnt for the preprtion of nnosuspension. The nnosuspension ws less thn 1 nm in prtile size nd dispersed uniformly with high zet potentil vlue nd exellent stility. The nnosuspension produed y the melt emulsifition-hph voids the use of orgni solvents nd redues the use of surftnts ompred with EC nd ME nd ould e pplile to vrious pestiides with melting points elow oiling point of wter. Therefore, this kind of formultion is perspetive in plnt protetion for improving iovilility nd reduing residul pollution of pestiide in griulturl produts nd environment.

7 Journl of Nnomterils 7 Lmd-yhlothrin onentrtion (%) dy 7 dys t C 14 dys t 54 C Figure 9: The hemil stility of the nnosuspension under different storge onditions. Sme letter t eh dt indites tht there is no signifint differene ording to Dunn s multiple rnge test t P <.5. Nnoprtiles fter 14 dys t 54 C Nnoprtiles fter 7 dys t C θ (deg) Nnoprtiles Figure 1: X-ry diffrtion ptterns of lmd-yhlothrin nnosuspension fter storge. Conflit of Interests The uthors delre tht there is no onflit of interests regrding the pulition of this pper. Authors Contriution Zhenzhong Pn nd Bo Cui ontriuted eqully to this work. Aknowledgments The reserh ws supported y Mjor Ntionl Sientifi Reserh Progrm of Chin (no. 214CB9322), Bsi Sientifi Reserh Foundtion of Ntionl Non-Profit Sientifi Institute of Chin (no. BSRF2146), Ntionl 863 progrm of the People s Repuli of Chin (no. 211AA1A21), the 12th Five-Yer Pln Projet of Siene nd Tehnology Support of Chin (214BAD14B2 nd 213BAC9B1), nd Reserh nd Development of Industril Tehnology Speil t Jilin Provinil Development nd Reform Commission (213C1). Referenes [1] Y.Ci,Y.J.Wen,X.L.Hnetl., Reserhprogressofnno-TiO 2 otnil pestiide, Chinese Journl of Hygieni Insetiides nd Equipments,vol.19,no.1,pp.73 79,213. [2]A.Goswmi,I.Roy,S.Sengupt,ndN.Denth, Novel pplitions of solid nd liquid formultions of nnoprtiles ginst inset pests nd pthogens, Thin Solid Films, vol. 519, no.3,pp ,21. [3]Z.Z.Pn,C.Cui,H.X.Cuietl., Progressonpestiide nnosuspension nd its preprtion methods, Chinese Journl of Pestiide Siene,vol.16,no.6,pp ,214. [4] S. M. D Addio nd R. K. Prud homme, Controlling drug nnoprtile formtion y rpid preipittion, Advned Drug Delivery Reviews,vol.63,no.6,pp ,211. [5] V. Ghormde, M. V. Deshpnde, nd K. M. Pknikr, Perspetives for nno-iotehnology enled protetion nd nutrition of plnts, Biotehnology Advnes, vol. 29, no. 6, pp , 211. [6]C.H.Anjli,S.SudheerKhn,K.Mrgulis-Goshen,S.Mgdssi, A. Mukherjee, nd N. Chndrsekrn, Formultion of wter-dispersile nnopermethrin for lrviidl pplitions, Eotoxiology nd Environmentl Sfety,vol.73,no.8,pp , 21. [7] N.Elek,R.Hoffmn,U.Rviv,R.Resh,I.Ishy,ndS.Mgdssi, Novluron nnoprtiles: formtion nd potentil use in ontrolling griulturl inset pests, Colloids nd Surfes A: Physiohemil nd Engineering Aspets, vol.372,no.1 3,pp , 21. [8] R. S. Suresh Kumr, P. J. Shiny, C. H. Anjli et l., Distintive effets of nno-sized permethrin in the environment, Environmentl Siene nd Pollution Reserh, vol.2,no.4,pp , 213. [9]H.Zeng,X.F.Li,G.Zhng,ndJ.Dong, Preprtionnd hrteriztion of et ypermethrin nnosuspensions y diluting O/W miroemulsions, JournlofDispersionSiene nd Tehnology,vol.29,no.3,pp ,28. [1] K. Kwkmi, Modifition of physiohemil hrteristis of tive phrmeutil ingredients nd pplition of supersturtledosgeformsforimprovingiovililityofpoorly sored drugs, Advned Drug Delivery Reviews, vol.64,no. 6, pp , 212. [11] J. P. Möshwitzer, Drug nnorystls in the ommeril phrmeutil development proess, Interntionl Journl of Phrmeutis,vol.453,no.1,pp ,213. [12] B. Sun nd Y. Yeo, Nnorystls for the prenterl delivery of poorly wter-solule drugs, Current Opinion in Solid Stte nd Mterils Siene,vol.16,no.6,pp ,212. [13] L. B. Wu, J. Zhng, nd W. Wtne, Physil nd hemil stility of drug nnoprtiles, Advned Drug Delivery Reviews,vol.63,no.6,pp ,211. [14] P. Koek, S. Bumgrtner, nd J. Kristl, Preprtion nd evlution of nnosuspensions for enhning the dissolution of poorly solule drugs, Interntionl Journl of Phrmeutis, vol.312,no.1-2,pp ,26. [15] C. M. Kek nd R. H. Müller, Drug nnorystls of poorly solule drugs produed y high pressure homogenistion,

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9 Journl of Nnotehnology Interntionl Journl of Interntionl Journl of Corrosion Polymer Siene Smrt Mterils Reserh Journl of Composites Journl of Metllurgy BioMed Reserh Interntionl Nnomterils Sumit your mnusripts t Journl of Mterils Journl of Nnoprtiles Nnomterils Journl of Advnes in Mterils Siene nd Engineering Journl of Journl of Nnosiene Sientifi Journl of Cotings Crystllogrphy The Sientifi World Journl Journl of Journl of Textiles Cermis Interntionl Journl of Biomterils