Optimization of Drug Encapsulation in Chitosan Microspheres by Coaxial Electrospraying Process

Document Type : Research Article


1 Chemical Engineering Department, Faculty of Engineering, Razi University, P.O. Box 6714967346 Kermanshah, I.R. IRAN

2 Department of Pharmaceutics, School of Pharmacy, Kermanshah University of Medical Sciences, P.O. Box 671547141 Kermanshah, I.R. IRAN


Over decades, micro and nanoparticles were developed as biodegradable carrier or scaffolds to deliver and control a release of various therapeutic agents like drugs, proteins, cells, and genes. In the present study, production of chitosan microparticles and simultaneously, loading retinoic acid in the microspheres using coaxial electrospray method was statistically evaluated by response surface methodology. The results showed that the particle size and the morphology of produced microspheres may be controlled by changing some experimental conditions like the concentration of chitosan (X1), flow rate of the retinoic acid stream (X2), chitosan to the retinoic acid ratio (X3), and intensity of the electrical force (X4). The optimized condition to achieve a lowest particles size and narrow size distribution was found at 3%w/v chitosan, 0.1 mL/h flow rate of retinoic acid, the ratio of chitosan to retinoic acid equal to 6, and under a voltage of 10.7 kV. The stability of the produced microspheres chitosan in nutrient broth was studied for 10 days. The acceptable stability of the microspheres may allow them to be studied in vivo.


[1] امیدی، مرضیه؛ شجاع الساداتی، سید عباس ؛ مرسلی، علی، بررسی بارگذاری و رهایش کنترل شده یک داروی ضد آریتمی قلبی در یک چارچوب فلز آلی، نشریه شیمی و مهندسی شیمی ایران.  (2) 33: 21 تا 25 (1393).
[2] Strebhardt K., Ullrich A., Paul Ehrlich’s Magic Bullet Concept : 100 Years of Progress. Nat. Rev. Cancer, 8: 473–480 (2008)
[3] سروشنیا، آرزو؛ گنجی، فریبا؛ تقیزاده، سید مجتبی، تأثیر متغیرهای فرمول­بندی بر عبورپوستی میکرو امولسیون دسموپرسین استات. نشریه شیمی و مهندسی شیمی ایران،  (2) 33:  27 تا 32 (1393).
[4] Weigl B., Domingo G., LaBarre P., Gerlach J., Towards Non- and Minimally Instrumented, Microfluidics-based Diagnostic Device, Lab. Chip., 8(12): 1999-2014 (2008)
[6] Zamani M., Prabhakaran M. Ramakrishna P.S., Advances in Drug Delivery via Electrospun and Electrosprayed Nanomaterials, Int. J. Nanomedicine, 8: 2997–3017 (2013)
[7] Loscertales I.G., Barrero A., Guerrero I., Cortijo R., Marquez M., Ganan-Calvo A.M., Micro/Nano Encapsulation via Electrified Coaxial Liquid Jets, Science, 295(5560): 1695-1698 (2002)
[8] Mei F., Chen D.R., Operational Modes of Dual-capillary Electrospraying and the Formation of the Stable Compound Cone-jet Mod, Aerosol Air Qual. Res., 8(2): 218–232 (2008)
[9] Chang M.W., Stride E., Edirisinghe M., A New Method for the Preparation of Monoporous Hollow Microspheres, Langmuir, 26(7): 5115–5121 (2010).
[10] Enayati M., Ahmad Z., Stride E., Edirisinghe M., One-step Electrohydrodynamic Production of Drug-loaded Micro-and Nanoparticles, J. R. Soc. Interface, 7: 667–675 (2010)
[11] Lee Y.H., Mei F., Bai M.Y., Zhao S., Chen D.R., Release Profile Characteristics of Biodegradable-polymer-coated Drug Particles Fabricated by Dual-capillary Electrospray, J. Control. Release, 145: 58–65 (2010)
[12] Enayati M., Farook U., Edirisinghe M., Stride E., Electrohydrodynamic Preparation of Polymeric Drug-carrier Particles: Mapping of the Process, Int. J. Pharm., 404: 110–115 (2011).
[13] Si T., Zhang L., Li G., Roberts C.J., Yin X., Xu R., Experimental Design and Instability Analysis of Coaxial Electrospray Process for Microencapsulation of Drugs and Imaging Agents, J. Biomed. Opt., 18: 075003 (2013)
[14] Park S., Hwang S., Lee J., pH-responsive Hydrogels from Moldable Composite Microparticles Prepared by Coaxial Electro-spray Drying, Chem. Eng. J., 169: 348–357 (2011). 
[15] Varmira K., Habibi A., Moradi S. Bahramian E., Statistical Optimization of Airlift Photobioreactor for High Concentration Production of Torularhodin Pigment, Biocatal. Agric. Biotechnol., 8 197–203 (2016).
[16] Zhang, L. Huang J., Si T., Xu R.X., Coaxial Electrospray of Microparticles and Nanoparticles for Biomedical Applications, Expert Rev. Med. Devices, 9(6): 595-612 (2012)
[18] Park I., Kim W., Kim S.S., Multi-jet Mode Electrospray for Non-conducting Fluids Using Two Fluids and a Coaxial Grooved Nozzle, Aerosol Sci. Technol., 45: 629-634 (2011)
[19] Xu Y., Hanna M.A., Morphological and Structural Properties of Two-phase Coaxial Jet Electrosprayed BSA-PLA Capsules, J. Microencapsul., 25: 469-477 (2008)
[20] Christe Sonia Mary M., Sasikumar, S., Sodium Alginate/Starch Blends Loaded with Ciprofloxacin Hydrochloride as a Floating Drug Delivery System - In Vitro Evaluation, Iran J. Chem. Chem. Eng. (IJCCE), 34(2): 25-31 (2015)
[21] Kim D.G., Choi C., Jeong Y-I., Jang M.K., Nah J.W., Kang S.K., Bang M.S., All-trans Retinoic Acid-associated Low Molecular Weight Water-soluble Chitosan Nanoparticles Based on Ion Complex, Macromol. Res., 14: 66-72 (2006)