Application of D-Optimal Mixture Design to Optimization and Formulation of Erythropoietin in Nanoparticles Drug Delivery System
DOI:
https://doi.org/10.22146/ijp.3431Keywords:
Erythropoietin, Nanoparticles, D-optimal mixture design, ChitosanAbstract
Erythropoietin (EPO) is a glycoprotein hormone used to treat anemia in patients with chronic renal failure in an injection dosage form. Drug delivery systems with nanoparticles technology have a high potential in increasing protein stability, prolonging the duration of the therapeutic effect, and the application without injection. This study aims to optimize the formulation of erythropoietin nanoparticle oral preparation using the D-optimal mixture design. This study is to determine the concentration range of chitosan and pectin as a base for nanoparticles. The D-optimal mixture design optimizes the erythropoietin nanoparticles by selecting the nanoparticle base composition as an independent factor and nanoparticle characterization as a response. Nanoparticles in the optimal formula were characterized, including particles size, polydispersity index (PDI), zeta potential, and encapsulation efficiency. The data were analyzed by using ANOVA contained in the Design Expert® software to get the optimum formula. The optimization showed that the optimal formula was that using 0,10% chitosan and 0,010% of pectin. Nanoparticle loaded erythropoietin produced with 278,8 nm of particle size, 0,38 of PDI, 27,0 mV of zeta potential, and 87,32% entrapment efficiency. In this study of the D-optimal mixture design, and optimize and prepare the erythropoietin nanoparticles
References
Bulmer C, Margaritis A, Xenocostas A. 2012. Production and characterization of novel chitosan nanoparticles for controlled release of rHu-Erythropoietin. Biochemical Engineering Journal. 68: 61–69.
Charalabidis A, Sfouni M, Bergström C, Macheras P. 2019. The Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS): Beyond guidelines. Int J Pharm. 566: pp 264–81.
Chen J, Yang W.-L, Li G, Qian J, Xue J-L, Fu S.-K. 2004. Transfection of mEpo gene to intestinal epithelium in vivo mediated by oral delivery of chitosan-DNA nanoparticles. World Journal of Gastroenterology. 10: 112–116.
Das S CA. 2011. Recent Advances in Lipid Nanoparticle Formulations with Solid Matrix for Oral Drug Delivery. AAPS PharmSciTech.12:62– 76
Egrie JC, Browne JK. 2001. Development and characterization of novel erythropoiesis stimulating protein (NESP). British Journal of Cancer. 84: 3–10.
Elliott S, Pham E, Macdougall IC. 2008. Erythropoietins: a common mechanism of action. Experimental Hematology. 36: 1573–1584.
Fayed BE, Tawfik AF, Yassin AEB. 2012. Novel erythropoietin-loaded nanoparticles with prolonged in vivo response. Journal of Microencapsulation. 29: 650–656.
Florence AT. 1997. The oral absorption of micro- and nanoparticulates: neither exceptional nor unusual. Pharmaceutical Research. 14: 259–266.
Jelkmann W. 2008. Developments in the therapeutic use of erythropoiesis stimulating agents. British Journal of Haematology. 141: 287–297.
Khasenbekova Z, Gulayev A, Nechayeva E, Nurgozhin T, Zhumadilov Z. 2013. Study of the erythropoiesis activity of nano-encapsulated forms of erythropoietin. Central Asian Journal of Global Health. 2: 110.
Kusuma TM. 2016. Formulasi nanopartikel insulin dengan teknik gelasi ionik menggunakan polimer kitosan bobot molekul sedang dan pektin, Tesis. Fakultas Farmasi. Universitas Gadjah Mada.
Maitani Y, Hazama M, Tojo Y, Nagai T, Shimoda N. 1996. Oral Administration of Recombinant Human Erythropoietin in Liposomes in Rats: Influence of Lipid Composition and Size of Liposomes on Bioavailability.Journal of Pharmaceutical Sciences. 85: 440–445.
Martien R, Loretz B, Sandbichler AM, Schnürch AB. 2008. Thiolated chitosan nanoparticles: transfection study in the Caco-2 differentiated cell culture. Nanotechnology.19: 1-9.
Mishra RK, Banthia AK, Majeed ABA. 2012. Pectin Based Formulations For Biomedical Applications : A review. Asian Journal of Pharmaceutical and Clinical Research. 5: 1–7.
Mohanraj VJ, Chen Y. 2006. Nanoparticles. A Review. TJPR.5: 561-573.
Smith J, Wood E, Dornish M. 2004. Effect of chitosan on epithelial cell tight junctions. Pharmaceutical Research. 21: 43–49.
Tamadon MR, Beladi-M SS. 2013. Erythropoietin; a review on current knowledge and new concepts. Journal of Renal Injury Prevention. 2: 119–121.
Tiyaboonchai W. 2003. Chitosan nanoparticles: A promising system for drug delivery. Naresuan University Journal. 11: 51–66.
Vllasaliu D, Exposito-H R, Heras A, Casettari L, Garnett M, Illum L. 2010. Tight junction modulation by chitosan nanoparticles: comparison with chitosan solution. International Journal of Pharmaceutics. 400: 183–193.
Wu Y, Yang W, Wang C, Hu J, Fu S. 2005. Chitosan nanoparticles as a novel delivery system for ammonium glycyrrhizinate. International Journal of Pharmaceutics. 295: 235–245.
Yeh T-H, Hsu L-W, Tseng MT, Lee P-L, Sonjae K, Ho Y-C. 2011. Mechanism and consequence of chitosan-mediated reversible epithelial tight junction opening. Biomaterials. 32: 6164–6173.
Yin H, Blanchard KL. 2000. DNA methylation represses the expression of the human erythropoietin gene by two different mechanisms. Blood. 95: 111–119.


