Electrospray method: processing parameters influence on morphology and size of pcl particles - Linh Viet Nguyen Vu

Journal of Science and Technology 55 (1B) (2017) 209–215 ELECTROSPRAY METHOD: PROCESSING PARAMETERS INFLUENCE ON MORPHOLOGY AND SIZE OF PCL PARTICLES Linh Viet Nguyen–Vu1, 2, *, Nguyen Hao Tran1, Dai Phu Huynh1, 2 1Faculty of Materials Technology, HCMUT–VNUHCM 268 Ly Thuong Kiet Street, Ward 14, District 10, Ho Chi Minh City, Vietnam 2National Key Laboratory of Polymer and Composite Materials, HCMUT–VNUHCM 268 Ly Thuong Kiet Street, Ward 14, District 10, Ho Chi Minh City,Vietnam *Email: nguyenvuvietlinh@hcmut.edu.vn Received: 30 December 2016; Accepted for publication: 6 March 2017 ABSTRACT The polymeric microparticles using electrospray technique have been used effectively as the drug carrier, whereby controlled release of drug. The electrosprayed particles morphology and size dictated the degradation of polymer matrix, therefore they influenced the release profile from drug loaded microparticles. The effects of electrospray processing parameters (flow rate, applied voltage and distance from the tip of needle to collector) on morphology and size of polycaprolactone (PCL) particles were investigated by scanning electron microscopy (SEM) and ImageJ software. In this research, the PCL solution was prepared by dissolving PCL in Dichloromethane at 4.5 % solution. In addition, processing parameters such as the flow rate (0.5 mL/h, 1 mL/h, 1.5 mL/h, 2 mL/h and 4 mL/h), the applied voltage (15 kV, 18 kV and 24 kV) and the collecting distance (15 cm, 20 cm, and 25 cm) were changed to examine the effects of them on size and morphology of PCL particles. The results indicated that at the suitable electrospraying parameters (18 kV, 1.5 mL/h, 20–25 cm), microparticles have obtained the uniform and stable morphology while at higher flow rate (2 mL/h and 4 mL/h), the particles were deformed and had bigger size. Keywords: morphology, electrospray, microparticles, polycaprolactone. 1. INTRODUCTION Electrospray method is a one–step process to fabricate biodegradable polymer microparticles with appropriate features such as size and morphology for drug carrier applications. Morphology and structure of electroprayed particles influence the release of drugs. Therefore, size and morphology controlled microparticles was able to control the release of drugs [1–4]. Some main factors which affect morphology (such as polymer concentration and solvent) or influence size and size distribution of particles (such as applied voltage, flow rate and collecting distance) were described in many studies. For instances, size and morphology of poly(lactic/glycolic) acid (PLGA) particles were controlled by adjusting solvent, molecular Electrospray method: processing parameters influence on morphology and size of PCL particles 210 weight, nozzle diameter and flow rate as these studies of Yao [5], Meng [6] and Jafari– Nodoushan [7]. Other polymers were used to fabricate electrosprayed microspheres with homogeneous and stable morphology such as chitosan [8, 9], polylactide acid (PLA) and PCL (Polycaprolactone) [1, 10, 11]. In drug delivery applications, polymer types were chosen based on their desirable properties, and then the release of drug from the polymer matrix. Polyester such as PLGA, PLA and PCL are degraded by hydrolysis of ester linkage. The degradation of PLGA and PLA is faster than PCL since they have more ester groups in their structure than PCL. Therefore, PLGA and PLA particles were suitable for shorter time drug delivery while PCL particles were effective for longer time system due to the slow degradation of PCL [12, 13]. This research investigated the effects of electrosprayed processing parameters such as flow rate, the applied voltage and the collecting distance on the morphology and size of PCL microparticles. The particles morphology was observed by SEM imagines. Size and size distribution of particles were evaluated by ImageJ and Minitab software. 2. MATERIALS AND METHODS 2.1. Materials Dichloromethane (DCM) was purchased from Prolabo – France, 99 % purified. Polycaprolactone (PCL) (Mw = 75 – 90 kDa) was purchased from Sigma–Aldrich. PCL pellets were dissolved in DCM with 4.5 % concentration (w/w). 2.2. PCL microparticles production by electrospraying The polymeric solutions were stirred using a magnetic stirrer for 2–3 h at room temperature. Then, the PCL solution was prepared in a 20 mL syringe and set up in a pump with the adjustable flow rate (Micropump Top–5300, UK, flow rate from 0.1 mL/h – 999.9 mL/h). The high voltage was applied to stainless steel needle (type Gauge 20G) on top of the syringe and the collector plate which was covered with aluminum foil. When the electrosprayed droplet flew from the tip of the needle to the collector, the solvent evaporated and solid microparticles were collected in aluminum foil. The processing parameters were adjusted by changing the flow rate (0.5, 1, 1.5, 2 and 4 mL/h), a high voltage (15, 18 and 24 kV) and collecting distance (15, 20 and 25 cm) during spraying. This process was carried out at room temperature. After electrospraying, the PCL microparticles were dried at room temperature for 2 days to remove solvent completely. 2.3. Characteristics of electrosprayed particles Morphology of microparticles was observed by the Hitachi S–4800 Scanning Electron Microscopy (SEM) – Japan at Nanotechnology Laboratory, R&D Center, Saigon Hi–tech Park, Vietnam. Samples were platinum coated by using a sputter coater under vacuum environment. The accelerating voltage of SEM was 5 kV during scanning. The diameter of the electrosprayed particles was measured by using standard SEM images coupled with the ImageJ program (v.1.50i of National Institute of Health, USA). Then the Minitab Software (version 17.1.0 of Minitab Inc., Australia) was operated to calculate mean size and size distribution of microparticles. 3.1 (a flo 1 m de of 13 F eje (0. . Effect of f Figure 1. SE ) 0.5 mL/h, (b The SEM w rate of 0.5 L/h to 4 m formed and particles (F .32 µm when Table 1. Av Electros low rate (mL/h) d 1.5 1.5 1.5 1.5 1.5 0.5 1.0 2.0 4.0 At the sam cted from th 5 mL/h) cau low rate on M images (a ) 1 mL/h, (c) rate images sho mL/h (Figu L/h (Figure aggregated w igure 1d, e) the flow ra erage size and praying param Collecting istance (cm) 20 20 20 15 25 20 20 20 20 e period o e tip of the sed small d 3. RES size and mo –e) of PCL m 1.5 mL/h, (d) (collecting d wed that the re 1a). Mos 1b, c, d, e hen they in . The averag te increased standard dev eters Applied voltage (kV) 15 18 24 18 18 18 18 18 18 f time, with needle incr roplet and h Linh Viet Ng ULT AND rphology o icroparticles 2 mL/h, (e) 4 istance: 20 cm irregular an t of micropa ). However fluence the e diameter from 0.5 mL iation of PCL Number of stud 50 50 50 40 50 50 50 50 17 higher flow eased so the igh charge d uyen–Vu, N DISCUSSIO f PCL parti of 4.5% PCL mL/h, (f) dia , voltage: 18 d heterogen rticles were , at 2 mL/h collector sin of particles /h to 4 mL/ particles in d particles ied A 0 0 0 0 0 0 0 0 0 rate (2 mL size of par ensity, the s guyen Hao N cles in DCM with meter of part kV, 20G). eous particle spherical sh and 4 mL/ ce the solve was increas h (Figure 1f) ifferent elecs verage diame (µm) 9.034 8.454 6.320 11.730 7.934 4.347 8.176 11.702 13.32 /h, 4 mL/h), ticles was b mall particle Tran, Dai Ph different flow icle of mentio s were form ape at flow h, the partic nt still prese ed from 4.3 . tropraying pr ter Standard (µ 1.3 1.3 1.3 2.3 1.7 1.2 1.6 2.2 1.8 the solution igger. Low s were gene u Huynh 211 rate ned flow ed at the rate from les were nt inside 5 µm to ocess. deviation m) 49 29 57 57 59 42 23 26 74 volume flow rate rated by Ele 21 str an µm 3.2 18 gau par str 8.4 the Fig Fig ctrospray m 2 ong Coulom d 1.5 mL/h. ) (Table 1). . Effect of a SEM ima and 24 kV) ge (20G), c ticles decre ength increa According 5 µm and 6 m was appr ure 2. SEM i (a, d) 15 kV, ure 3. The ef ethod: proce b fission. Th The standard Therefore, f pplied volta ges showed whereas 4.5 ollecting di ased when th sing at highe to Table 1 .32 µm whe oximately (1 mages and th (b, e) 18 kV, fect of the ap col ssing param e homogene deviation o low rate was ge on size a that the mic % PCL con stance (20 c e applied v r applied vo , the averag n applied v .35, 1.33 an e size distribu (c, f) 24 kV (c plied voltage lecting distan eters influe ous microsp f particles s fixed at 1.5 nd morpho rospheres w centration an m) were fix oltage increa ltage. e diameters oltage was i d 1.36 µm). tion histogram ollecting dist DCM, 20 on the averag ce: 20 cm, flo nce on morp heres were ize using 1.5 mL/h in nex logy of PCL ere generate d parameter ed (Figure 2 sed (Figure of microsph ncreased, ho s of PCL pa ance: 20 cm, G). e diameter of w rate: 1.5 m hology and s obtained at f mL/h is the t experimen particles d at various s of flow ra ). The avera 3). 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The unifor rd deviation m the tip o nd the size di ) 15 cm, (b, e 4.5 e parameter of 1.5 mL/h the tip of nee of 15 cm, th ile microsp enon is tha s. Thus th robeads, fib cm, the poly article morp rphology of particles bec d secondary the average s increased divided drop m size of pa is 1.329) so Linh Viet Ng f needle to stribution hist ) 20 cm, (c, f) % PCL in DC s, 4.5% PC , the morph dle to colle ere was a v heres were t the electro e morphol er and parti mer chains hology was the particle ame broade droplets. diameter of gradually (1 lets into sma rticles whic that it was t uyen–Vu, N collector on ograms of PC 25 cm (volta M, 20 G). L in DCM, ology of m ctor. ariety of par only forme spray was in ogy of par cles with a had time t spherical. H s turned to h r than at 20 particles re 5–25 cm) (F ller particle h using coll he optimized guyen Hao size and m L micropartic ge: 18 kV, flo applied volta icroparticles ticle morpho d at 20 cm multi–jet m ticles was tail. Further o diffuse in owever, wh eterogeneou cm (Figure 4 duced from igure 5). B s when they ecting distan value in thi Tran, Dai Ph orphology les with diffe w rate: 1.5 m ge of 18 kV was differe logy such a (Figure 4a, ode at 15 c heterogene more, incre side the dro en the dista s spheres (F d, e, f), con 11.73–7.93 µ ecause of in flew from th ce of 20 cm s research. u Huynh 213 of PCL rent L/h, , needle nt when s sphere, b). The m due to ous and asing the plet and nce was igure 4c) sequence m when creasing e needle was the Ele 21 par siz de app inc Th fab Ac HC 1 2 3 4 5 ctrospray m 4 Figure 5. Th The flow ticles. Incre e, but the a sirable micro lied voltage reased whe e results de ricating mo knowledgmen M, under gra . Bock N reproduc applicati . Xu Y., polylacti profile o . Enayati producti Interface . Bock N therapeu 1551. . Yao J., process 1002. ethod: proce e effect of di particles (4.5 rate is a asing flow r ggregation h spheres we of 18 kV a n the flow r monstrated nodispersed t. This resea nt number T– ., Woodruff ible metho ons, Polyme Hanna M. de: Effects f particles, I M., Ahmad on of drug 7 (45) (201 ., Dargavill tic molecule Lim L. K., for polymeri ssing param stance from th % PCL in DC 4 main proces ate from 0.5 appened wh re formed u nd collectin ate increase that the e spherical mi rch is funded CNVL–2016 M. A., Hu d for pro rs 3 (1) (201 A. – Elec of formulati nternational Z., Stride –loaded mi 0) 667–675. e T. R., W s: state of th Xie J., Hua c particle fa eters influe e tip of need M, flow rate . CONCLU sing param mL/h to 2 en the flow sing a suitab g distance o d and the v lectrosprayin croparticles by Ho Chi –10. REFEREN tmacher D. duction of 1) 131–149 trospray en ons on morp journal of p E., Edirisi cro–and na oodruff M e art, Progr J., Wang C brication, Jo nce on morp le to collector : 1.5 mL/h, vo SION eters effects mL/h cause rate increa le set of pa f 20 cm. Th oltage and t g techniqu . Minh City U CES W., Dargav polymeric capsulation hology, enc harmaceutic nghe M. – noparticles, . A. – Ele ess in polym . –H. – Ch urnal of aer hology and s on the averag ltage: 18 kV, morpholog d bigger ele sed to 4 mL rameters: flo e size of th he collecting e was an e niversity of ille T. R. microsphe of water–s apsulation e s 320 (1) (20 One–step Journal of ctrospraying er science 3 aracterizatio osol science ize of PCL e diameter o 20G). y of electr ctrosprayed /h. Furtherm w rate of 1 e PCL mic distance d ffective me Technology – Electrospr res for bi oluble prot fficiency an 06) 30–36. electrohydro the Royal of polym 7 (11) (201 n of electro 39 (11) (20 particles f PCL osprayed particles ore, the .5 mL/h, rosphere ecreased. thod for – VNU – aying, a omedical ein with d release dynamic Society ers with 2) 1510– spraying 08) 987– Linh Viet Nguyen–Vu, Nguyen Hao Tran, Dai Phu Huynh 215 6. Meng F., Jiang Y., Sun Z., Yin Y., Li Y. – Electrohydrodynamic liquid atomization of biodegradable polymer microparticles: Effect of electrohydrodynamic liquid atomization variables on microparticles, Journal of applied polymer science 113 (1) (2009) 526–534. 7. Jafari–Nodoushan M., Barzin J., Mobedi H. – Size and morphology controlling of PLGA microparticles produced by electro hydrodynamic atomization, Polymers for Advanced Technologies 26 (5) (2015) 502–513. 8. Nguyen T. D., Hoan D. N., Huynh D. P. – Research on micro–nano chitosan spheres fabricated by electrospraying for insulin delivery system, Journal of Science and Technology 53 (2B) (2015) 11–20. 9. Arya N., Chakraborty S., Dube N., Katti D.S. – Electrospraying: a facile technique for synthesis of chitosan–based micro/nanospheres for drug delivery applications, Journal of Biomedical Materials Research Part B: Applied Biomaterials 88 (1) (2009) 17–31. 10. Chakraborty S., Liao I. –C., Adler A., Leong K. W. – Electrohydrodynamics: a facile technique to fabricate drug delivery systems, Advanced Drug Delivery Reviews 61 (12) (2009) 1043–1054. 11. Enayati M., Ahmad Z., Stride E., Edirisinghe M. – Size mapping of electric field–assisted production of polycaprolactone particles, Journal of the Royal Society Interface 7 (2010) S393–S402. 12. Xie J., Jiang J., Davoodi P., Srinivasan M. P., Wang C. –H. – Electrohydrodynamic atomization: A two–decade effort to produce and process micro–/nanoparticulate materials, Chemical Engineering Science 125 (2015) 32–57. 13. Gunatillake P., Adhikari R. – Biodegradable synthetic polymers for tissue engineering, European Cells & Materials 5 (2003) 1–16.