Production of polycaprolactone nanoparticles with low polydispersity index in a tubular recirculating system by using a multifactorial design of experiments

  • Gabriel Jaime Colmenares Roldán
  • Liliana María Agudelo Gomez
  • Jesús Antonio Carlos Cornelio
  • Luis Fernando Rodriguez
  • Rodolfo Pinal
  • Lina Marcela Hoyos Palacio
Research Paper


Encapsulation and controlled release of substances using polymeric nanoparticles require that these have a high reproducibility, homogeneity, and control over their properties (diameter and polydispersity), especially when they are to be used in medical, pharmaceutical, or nutritional applications among others. In conventional production systems, it is tough to ensure these characteristics; hence, the cost increases when we try to control these properties. This paper shows a comparison between a recirculating system and the standard nanoprecipitation technique for producing polymeric nanoparticles. In previous investigations, we evaluate the effect of recirculating flow and the ratio between the organic and aqueous phase. For this paper, we evaluated the effect of polymer and surfactant concentrations using a multifactorial design of experiments on the recirculating system and on the standard nanoprecipitation system. The response of the design was the average diameter of the nanoparticles and polydispersity index. Finally, we found that the polymer and surfactant concentrations could change the average diameter and polydispersity index of the nanoparticles obtained. On the other hand, it was found that the effect of the polymer concentration was stronger than the surfactant concentration to reduce the average diameter of the nanoparticles. The results of the present study show that the proposed recirculation system presents a high potential to produce polymer nanoparticles with good morphological characteristics, particle size distributions in the nano range, and with a low polydispersity. The average mean size of nanoparticles of polycaprolactone for the design using the recirculating system was of 61 to 140 nm and the values of polydispersity index PDI for this design were between 0.097 and 0.22, while for the design using the standard nanoprecipitation technique, the obtained diameters were 74 to 176 nm and the polydispersity was between 0.26 and 0.41.


Nanoparticles Nanocapsules Nanoprecipitation Polymers Surfactant Nanoencapsulation 



The authors thank the Universidad Pontificia Bolivariana, to Ruta n, and Colciencias for the financial support provided to investigators and Professor Teresa Carvajal and Christopher J. Gilpin of Purdue University for facilitating the characterizations of the samples by DLS and TEM.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Anandharamakrishnan C (2014) In: Hartel RW, Peter Clark J, Finley JW, Rodriguez-Lazaro D, Topping D (eds) Techniques for nanoencapsulation of food ingredients. Springer New York, New York Retrieved ( Scholar
  2. Colmenares G, Agudelo L, Quintero Y, Hoyos L (2016) Synthesis of bioabsorbable polymeric nanoparticles for controlled drug release using a recirculating system. in XXV International Materials Research Congress. Cancun. Retrieved ( Roldan, Gabriel Jaime)
  3. Colmenares G, Agudelo L, Pinal R, Hoyos L (2017) Production of bioabsorbible nanoparticles of polycaprolactone by using a recirculating system. Pp. 395–98 in TechConnect World Innovation Conferences. TechConnect. Retrieved (
  4. Dash TK, Badireenath Konkimalla V (2012) Poly-Є-caprolactone based formulations for drug delivery and tissue engineering: a review. J Control Release 158(1):15–33 Retrieved ( Scholar
  5. Deveza L et al (2015) Microfluidic synthesis of biodegradable polyethylene-glycol microspheres for controlled delivery of proteins and DNA nanoparticles. ACS Biomater Sci Eng 1(3):157–165. CrossRefGoogle Scholar
  6. Fakirov S (ed) (2016) Nano-size polymers. Springer International Publishing, Cham. Google Scholar
  7. Grillo R et al (2012) Poly(e--caprolactone) nanocapsules as carrier systems for herbicides: physico-chemical characterization and genotoxicity evaluation. J Hazard Mater 231–232:1–9CrossRefGoogle Scholar
  8. Karnik R, Gu F, Basto P, Cannizzaro C, Dean L, Kyei-Manu W, Langer R, Farokhzad OC (2008) Microfluidic platform for controlled synthesis of polymeric nanoparticles. Nano Lett 8(9):2906–2912CrossRefGoogle Scholar
  9. Lepeltier E, Bourgaux C, Couvreur P (2014) Nanoprecipitation and the ‘Ouzo Effect’: application to drug delivery devices. Adv Drug Deliv Rev 71:86–97 Retrieved ( Scholar
  10. Lim JM et al (2014) Ultra-high throughput synthesis of nanoparticles with homogeneous size distribution using a coaxial turbulent jet mixer. ACS Nano 8(6):6056–6065CrossRefGoogle Scholar
  11. Malhotra S et al (2007) Use of an oncolytic virus secreting GM-CSF as combined oncolytic and immunotherapy for treatment of colorectal and hepatic adenocarcinomas. Surgery 141(4):520–529 Retrieved ( Scholar
  12. Marre S, Jensen KF (2010) Synthesis of micro and nanostructures in microfluidic systems. Chem Soc Rev 39(3):1183 Retrieved ( Scholar
  13. Mora-Huertas CE, Fessi H, Elaissari a (2010) Polymer-based nanocapsules for drug delivery. Int J Pharm 385(1–2):113–142CrossRefGoogle Scholar
  14. Obayemi JD, Danyuo Y, Dozie-Nwachukwu S, Odusanya OS, Anuku N, Malatesta K, Yu W, Uhrich KE, Soboyejo WO (2016) PLGA-based microparticles loaded with bacterial-synthesized prodigiosin for anticancer drug release: effects of particle size on drug release kinetics and cell viability. Mater Sci Eng C 66:51–65 Retrieved ( Scholar
  15. Othman R, Vladisavljević GT, Shahmohamadi H, Nagy ZK, Holdich RG (2016) Formation of size-tuneable biodegradable polymeric nanoparticles by solvent displacement method using micro-engineered membranes fabricated by laser drilling and electroforming. Chem Eng J 304:703–713 Retrieved ( Scholar
  16. Prieto C, Calvo L (2017) Supercritical fluid extraction of emulsions to nanoencapsulate vitamin E in polycaprolactone. J Supercrit Fluids 119:274–282 Retrieved ( Scholar
  17. Rao JP, Geckeler KE (2011) Polymer nanoparticles: preparation techniques and size-control parameters. Prog Polym Sci (Oxford) 36(7):887–913CrossRefGoogle Scholar
  18. Rose J, Auffan M, Proux O, Niviere V, Bottero JY (2012) In: Bhushan B (ed) Encyclopedia of nanotechnology. Springer Netherlands, Dordrecht Retrieved ( Scholar
  19. Salmani H, Bilibin AY (2016) Nanoprecipitation—miniemulsion polymerization combined method : a novel approach to synthesis drug loaded nanoparticles with tunable characteristics. Macromol Nanotechnol 84:631–641Google Scholar
  20. Schubert S, Delaney JT Jr, Schubert US (2011) Nanoprecipitation and nanoformulation of polymers: from history to powerful possibilities beyond poly(lactic acid). Soft Matter 7(5):1581–1588 Retrieved ( Scholar
  21. Shi J, Votruba AR, Farokhzad OC, Langer R (2010) Nanotechnology in drug delivery and tissue engineering: from discovery to applications. Nano Lett 10(9):3223–3230 Retrieved ( Scholar
  22. Valencia PM, Farokhzad OC, Karnik R, Langer R (2012) Microfluidic technologies for accelerating the clinical translation of nanoparticles. Nat Nanotechnol 7(10):623–629CrossRefGoogle Scholar
  23. Verderio P, Bonetti P, Colombo M, Pandolfi L, Prosperi D (2013) Intracellular drug release from curcumin-loaded PLGA nanoparticles induces G2 / M block in breast cancer cells. Biomacromolecules 14:672–682CrossRefGoogle Scholar
  24. Vladisavljević GT, Khalid N, Neves MA, Kuroiwa T, Nakajima M, Uemura K, Ichikawa S, Kobayashi I (2013) Industrial lab-on-a-chip: design, applications and scale-up for drug discovery and delivery. Adv Drug Deliv Rev 65(11–12):1626–1663CrossRefGoogle Scholar
  25. Zhang C, Pansare VJ, Prud’homme RK, Priestley RD (2012) Flash nanoprecipitation of polystyrenenanoparticles. Soft Matter 8(1):86–93 Retrieved ( ) CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Gabriel Jaime Colmenares Roldán
    • 1
    • 2
  • Liliana María Agudelo Gomez
    • 1
    • 2
  • Jesús Antonio Carlos Cornelio
    • 2
  • Luis Fernando Rodriguez
    • 2
  • Rodolfo Pinal
    • 3
  • Lina Marcela Hoyos Palacio
    • 1
    • 2
  1. 1.Grupo de Biología de Sistemas, Escuela de Ciencias de la SaludUniversidad Pontificia BolivarianaMedellínColombia
  2. 2.Grupo de investigación en nanotecnología y materialesNanomatMedellínColombia
  3. 3.Department of Industrial and Physical Pharmacy, College of PharmacyPurdue UniversityWest LafayetteUSA

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