Generic placeholder image

Pharmaceutical Nanotechnology


ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Research Article

Utilization of Microfluidics for the Preparation of Polymeric Nanoparticles for the Antioxidant Rutin: A Comparison with Bulk Production

Author(s): Hanh T.H. Vu, Sarah Streck, Sarah M. Hook and Arlene McDowell*

Volume 7 , Issue 6 , 2019

Page: [469 - 483] Pages: 15

DOI: 10.2174/2211738507666191019141049


Objective: To compare the characteristics of rutin-loaded PLGA (poly(lactic-coglycolic acid)) nanoparticles prepared using a single emulsion evaporation method (bulk method) and a nanoprecipitation method using microfluidics.

Methods: Rutin-loaded PLGA nanoparticles were produced using different methods and characterized for size, zeta potential, entrapment efficiency (EE) and drug loading (DL). A design of experiments approach was used to identify the effect of method parameters to optimize the formulation. DSC was used to investigate the solid-state characteristics of rutin and PLGA and identify any interactions in the rutin-loaded PLGA nanoparticles. The release of rutin from PLGA nanoparticles was examined in biorelevant media and phosphate buffer (PBS).

Results: The optimal formulation of rutin-loaded PLGA nanoparticles produced using a microfluidics method resulted in a higher entrapment efficiency of 34 ± 2% and a smaller size of 123 ± 4 nm compared to a bulk method (EE 27 ± 1%, size 179 ± 13 nm). The solidstate of rutin and PLGA changed from crystalline to amorphous with the preparation of rutin- loaded PLGA nanoparticles. More importantly, using microfluidics, rutin released faster from rutin-loaded PLGA nanoparticles in biorelevant media and PBS with higher burst release compared to the rutin release from the nanoparticles prepared by using the bulk method.

Conclusion: Rutin can be encapsulated in nanoparticles formulated with different methods with mean sizes of less than 200 nm. Microfluidics produced more uniform rutin-loaded PLGA nanoparticles with a higher EE, DL and faster release compared to a bulk production method.

Keywords: Antioxidant, design of experiments, microfluidics, PLGA nanoparticles, rutin, emulsion evaporation method.

Graphical Abstract
Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20(7): 933-56.
[] [PMID: 8743980]
Jiang H, Engelhardt UH, Thräne C, Maiwald B, Stark J. Determination of flavonol glycosides in green tea, oolong tea and black tea by UHPLC compared to HPLC. Food Chem 2015; 183: 30-5.
[] [PMID: 25863606]
Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002; 13(10): 572-84.
[] [PMID: 12550068]
Robak J, Gryglewski RJ. Flavonoids are scavengers of superoxide anions. Biochem Pharmacol 1988; 37(5): 837-41.
[] [PMID: 2830882]
Sun G, Wang W, Wu J. Pulse radiolysis study on the rutin and quercetin anions formation and their behaviours in N2-saturated ethanol solution. Radiat Phys Chem 1999; 55(3): 285-91.
Chen IL, Tsai YJ, Huang CM, Tsai TH. Lymphatic absorption of quercetin and rutin in rat and their pharmacokinetics in systemic plasma. J Agric Food Chem 2010; 58(1): 546-51.
[] [PMID: 19916501]
Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. J Pharm Sci 1985; 1(4): 331-2.
Poderoso JJ, Carreras MC, Lisdero C, Riobó N, Schöpfer F, Boveris A. Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles. Arch Biochem Biophys 1996; 328(1): 85-92.
[] [PMID: 8638942]
Tongjaroenbuangam W, Ruksee N, Chantiratikul P, Pakdeenarong N, Kongbuntad W, Govitrapong P. Neuroprotective effects of quercetin, rutin and okra (Abelmoschus esculentus Linn.) in dexamethasone-treated mice. Neurochem Int 2011; 59(5): 677-85.
[] [PMID: 21740943]
Mendes-Junior Ld, Monteiro MM, Carvalho AS, de Queiroz TM, Braga VA. Oral supplementation with the rutin improves cardiovagal baroreflex sensitivity and vascular reactivity in hypertensive rats. Appl Physiol Nutr Metab 2013; 38(11): 1099-106.
[] [PMID: 24053516]
Lin JP, Yang JS, Lin JJ, et al. Rutin inhibits human leukemia tumor growth in a murine xenograft model in vivo. Environ Toxicol 2012; 27(8): 480-4.
[] [PMID: 21254320]
Lee CC, Shen SR, Lai YJ, Wu SC. Rutin and quercetin, bioactive compounds from tartary buckwheat, prevent liver inflammatory injury. Food Funct 2013; 4(5): 794-802.
[] [PMID: 23584161]
Manach C, Morand C, Demigné C, Texier O, Régérat F, Rémésy C. Bioavailability of rutin and quercetin in rats. FEBS Lett 1997; 409(1): 12-6.
[] [PMID: 9199494]
Miyake K, Arima H, Hirayama F, et al. Improvement of solubility and oral bioavailability of rutin by complexation with 2-hydroxypropyl-beta-cyclodextrin. Pharm Dev Technol 2000; 5(3): 399-407.
[] [PMID: 10934740]
Erlund I, Kosonen T, Alfthan G, et al. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur J Clin Pharmacol 2000; 56(8): 545-53.
[] [PMID: 11151743]
Sharma S, Ali A, Ali J, Sahni JK, Baboota S. Rutin: therapeutic potential and recent advances in drug delivery. Expert Opin Investig Drugs 2013; 22(8): 1063-79.
[] [PMID: 23795677]
Makadia HK, Siegel SJ. Poly lactic-co-glycolic acid (PLGA) as biodegradable controlled drug delivery carrier. Polymers 2011; 3(3): 1377-97.
[] [PMID: 22577513]
Wischke C, Schwendeman SP. Principles of encapsulating hydrophobic drugs in PLA/PLGA microparticles. Int J Pharm 2008; 364(2): 298-327.
[] [PMID: 18621492]
Wang Y, Li P, Truong-Dinh Tran T, Zhang J, Kong L. Manufacturing tecnhiuques and surface engineering of polymer based nanoparticles for targeted drug delivery to cancer. Nanomaterials 2016; 6(2)E26
[] [PMID: 28344283]
Jain RA. The manufacturing techniques of various drug loaded biodegradable poly (lactide-co-glycolide) (PLGA) devices. Biomaterials 2000; 21(23): 2475-90.
[] [PMID: 11055295]
Chiesa E, Dorati R, Modena T, Conti B, Genta I. Multivariate analysis for the optimization of microfluidics-assisted nanoprecipitation method intended for the loading of small hydrophilic drugs into PLGA nanoparticles. Int J Pharm 2018; 536(1): 165-77.
[] [PMID: 29175645]
Donno R, Gennari A, Lallana E, et al. Nanomanufacturing through microfluidic-assisted nanoprecipitation: advanced analytics and structure-activity relationships. Int J Pharm 2017; 534(1-2): 97-107.
[] [PMID: 29017804]
Williams MS, Longmuir KJ, Yager P. A practical guide to the staggered herringbone mixer. Lab Chip 2008; 8(7): 1121-9.
[] [PMID: 18584088]
Lince F, Marchisio DL, Barresi AA. Strategies to control the particle size distribution of poly-ε-caprolactone nanoparticles for pharmaceutical applications. J Colloid Interface Sci 2008; 322(2): 505-15.
[] [PMID: 18402975]
Pitt JA, Kozal JS, Jayasundara N, et al. Uptake, tissue distribution, and toxicity of polystyrene nanoparticles in developing zebrafish (Danio rerio). Aquat Toxicol 2018; 194: 185-94.
[] [PMID: 29197232]
Derman S. Caffeic acid phenethyl ester loaded PLGA nanoparticles: effect of various process parameters in reaction yeild, encapsulation efficiency, and particle size. J Nanomater 2015; 2015: 12.
Belliveau NM, Huft J, Lin PJ, et al. Microfluidic synthesis of highly potent limit-size lipid nanoparticles for in vivo delivery of siRNA. Mol Ther Nucleic Acids 2012; 1 e37
[] [PMID: 23344179]
Kastner E, Kaur R, Lowry D, Moghaddam B, Wilkinson A, Perrie Y. High-throughput manufacturing of size-tuned liposomes by a new microfluidics method using enhanced statistical tools for characterization. Int J Pharm 2014; 477(1-2): 361-8.
[] [PMID: 25455778]
Vu HTH, Hook SM, Siqueira SD, Müllertz A, Rades T, McDowell A. Are phytosomes a superior nanodelivery system for the antioxidant rutin? Int J Pharm 2018; 548(1): 82-91.
[] [PMID: 29933062]
Song X, Zhao Y, Wu W, et al. PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: systematic study of particle size and drug entrapment efficiency. Int J Pharm 2008; 350(1-2): 320-9.
[] [PMID: 17913411]
Tefas LR, Tomuţă I, Achim M, Vlase L. Development and optimization of quercetin-loaded PLGA nanoparticles by experimental design. Clujul Med 2015; 88(2): 214-23.
[PMID: 26528074]
Keum CG, Noh YW, Baek JS, et al. Practical preparation procedures for docetaxel-loaded nanoparticles using polylactic acid-co-glycolic acid. Int J Nanomedicine 2011; 6: 2225-34.
[PMID: 22114486]
Liu K, Zhu Z, Wang X, et al. Microfluidics-based single-step preparation of injection-ready polymeric nanosystems for medical imaging and drug delivery. Nanoscale 2015; 7(40): 16983-93.
[] [PMID: 26415866]
Amoyav B, Benny O. Controlled and tunable polymer particles’ production using a single microfluidic device. Appl Nanosci 2018; 8(4): 905-14.
Bramosanti M, Chronopoulou L, Grillo F, Valletta A, Palocci C. Microfluidic-assisted nanoprecipitation of antiviral-loaded polymeric nanoparticles. Colloids Surf A Physicochem Eng Asp 2017; 532: 369-76.
Mandenius CF, Brundin A. Bioprocess optimization using design-of-experiments methodology. Biotechnol Prog 2008; 24(6): 1191-203.
[] [PMID: 19194932]
Narayanan K, Subrahmanyam VM, Venkata Rao J. A fractional factorial design to study the effect of process variables on the preparation of hyaluronidase loaded PLGA nanoparticles. Enzyme Res 2014; 2014 162962
[] [PMID: 25574384]
Jacobs C, Kayser O, Müller RH. Nanosuspensions as a new approach for the formulation for the poorly soluble drug tarazepide. Int J Pharm 2000; 196(2): 161-4.
[] [PMID: 10699709]
Karnik R, Gu F, Basto P, et al. Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett 2008; 8(9): 2906-12.
[] [PMID: 18656990]
Ma J, Lee SM, Yi C, Li CW. Controllable synthesis of functional nanoparticles by microfluidic platforms for biomedical applications - a review. Lab Chip 2017; 17(2): 209-26.
[] [PMID: 27991629]
Singh D, Rawat MS, Semalty A, Semalty M. Rutin-phospholipid complex: an innovative technique in novel drug delivery system- NDDS. Curr Drug Deliv 2012; 9(3): 305-14.
[] [PMID: 22283645]
Bailey NA, Sandor M, Kreitz M, Mathiowitz E. Comparison of the enthalpic relaxation of poly(lactide-co-glycolide) 50:50 nanospheres and raw polymer. J Appl Polym Sci 2002; 86(8): 1868-72.
Horosanskaia E, Minh NT, Dinh VT, Seidel-Morgenstern A, Lorenz H. Crystallization-based Isolation of pure rutin from herbal extract of Sophora japonica L. Org Process Res Dev 2017; 21(11): 1769-78.
Pimple S, Manjappa AS, Ukawala M, Murthy RSR. PLGA nanoparticles loaded with etoposide and quercetin dihydrate individually: in vitro cell line study to ensure advantage of combination therapy. Cancer Nanotechnol 2012; 3(1-6): 25-36.
[] [PMID: 26069494]
Feng S, Lu F, Wang Y, Suo J. Comparison of the degradation and release behaviors of poly (lactide-co-glycolide)-methoxypoly(ethylene-glycol) microspheres prepared with single- and double-emulsion evaporation methods. J Appl Polym Sci 2015; 132(19): 1-7.
Guo L-Y, Yan S-Z, Li Q, et al. Poly (lactic-co-glycolic) acid nanoparticles improve oral bioavailability of hypocrellin A in rat. RCS Adv 2017; 7(67): 42073-82.
Jovanovic SV, Steenken S, Tosic M, Marjanovic B, Simic MG. Flavonoids as antioxidants. J Am Chem Soc 1994; 116(11): 4846-51.
Li J, Jiang G, Ding F. The effect of pH on the polymer degradation and drug release from PLGA‐mPEG microparticles. J Appl Polym Sci 2008; 109(1): 475-82.

© 2022 Bentham Science Publishers | Privacy Policy