Water-in-Water Emulsion Based Synthesis of Hydrogel Nanospheres with Tunable Release Kinetics
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Abstract
Poly(ethylene glycol) (PEG) micro/nanospheres have several unique advantages as polymer based drug delivery systems (DDS) such as tunable size, large surface area to volume ratio, and colloidal stability. Emulsification is one of the widely used methods for facile synthesis of micro/nanospheres. Two-phase aqueous system based on polymer–polymer immiscibility is a novel approach for preparation of water-in-water (w/w) emulsions. This method is promising for the synthesis of PEG micro/nanospheres for biological systems, since the emulsion is aqueous and do not require organic solvents or surfactants. Here, we report the synthesis of nano-scale PEG hydrogel particles using w/w emulsions using phase separation of dextran and PEG prepolymer. Dynamic light scattering (DLS) and scaning electron microscopy (SEM) results demonstrated that nano-scale hydrogel spheres could be obtained with this approach. We investigated the release kinetics of a model drug, pregabalin (PGB) from PEG nanospheres and demonstrated the influence of polymerization conditions on loading and release of the drug as well as the morphology and size distribution of PEG nanospheres. The experimental drug release data was fitted to a stretched exponential function which suggested high correlation with experimental results to predict half-time and drug release rates from the model equation. The biocompatibility of nanospheres on human dermal fibroblasts using cell-survival assay suggested that PEG nanospheres with altered concentrations are non-toxic, and can be considered for controlled drug/molecule delivery.
Keywords
Dynamic Light Scattering Pregabalin Human Dermal Fibroblast Cumulative Release Dulbecco Modify Eagle MediumNotes
Acknowledgements
We would like to acknowledge Koç University Surface Science and Technology Center (KUYTAM) for SEM and UV–visible spectrophotometer. SK would like to acknowledge funding from Istanbul Rotary Club and Koc University Seed Grant.
References
- 1.N.A. Peppas, J.Z. Hilt, A. Khademhosseini, and R. Langer, Adv. Mater.-Deerfield Beach Then Weinheim- 18, 1345 (2006).CrossRefGoogle Scholar
- 2.F. Brandl, F. Sommer, and A. Goepferich, Biomaterials 28, 134 (2007).CrossRefGoogle Scholar
- 3.V. Crescenzi, L. Cornelio, C. Di Meo, S. Nardecchia, and R. Lamanna, Biomacromolecules 8, 1844 (2007).CrossRefGoogle Scholar
- 4.T. Bal, B. Kepsutlu, and S. Kizilel, J. Biomed. Mater. Res., Part A 102, 487 (2014).CrossRefGoogle Scholar
- 5.T. Bal, C. Nazli, A. Okcu, G. Duruksu, E. Karaoz, and S. Kizilel, J. Tissue Eng. Regen. Med. (2014). doi: 10.1002/term.1965.
- 6.Y.-H. Wu, H.B. Park, T. Kai, B.D. Freeman, and D.S. Kalika, J. Membr. Sci. 347, 197 (2010).CrossRefGoogle Scholar
- 7.G. Tan, J. Liao, C. Ning, and L. Zhang, J. Appl. Polym. Sci. 125, 3509 (2012).CrossRefGoogle Scholar
- 8.X.S. Wu and N. Wang, J. Biomater. Sci. Polym. Ed. 12, 21 (2001).CrossRefGoogle Scholar
- 9.H. Zhu and M.J. McShane. Chem. Commun. 2, 153 (2006).Google Scholar
- 10.T. Jung, W. Kamm, A. Breitenbach, E. Kaiserling, J. Xiao, and T. Kissel, Eur. J. Pharm. Biopharm. 50, 147 (2000).CrossRefGoogle Scholar
- 11.J.K. Oh, R. Drumright, D.J. Siegwart, and K. Matyjaszewski, Prog. Polym. Sci. 33, 448 (2008).CrossRefGoogle Scholar
- 12.F. Sultana, M. Manirujjaman, M.A. Imran-Ul-Haque, and S. Sharmin, J. Appl. Pharm. Sci. 3, S95 (2013).Google Scholar
- 13.H. Zhang, S. Mardyani, W.C. Chan, and E. Kumacheva, Biomacromolecules 7, 1568 (2006).CrossRefGoogle Scholar
- 14.S.K. Hobbs, W.L. Monsky, F. Yuan, W.G. Roberts, L. Griffith, V.P. Torchilin, and R.K. Jain, Proc. Natl. Acad. Sci. 95, 4607 (1998).CrossRefGoogle Scholar
- 15.L. Seymour, R. Duncan, J. Strohalm, and J. Kopeček, J. Biomed. Mater. Res. 21, 1341 (1987).CrossRefGoogle Scholar
- 16.S. Freiberg and X. Zhu, Int. J. Pharm. 282, 1 (2004).CrossRefGoogle Scholar
- 17.T.H. Kim, H.H. Jiang, C.W. Park, Y.S. Youn, S. Lee, X. Chen, and K.C. Lee, J. Controlled Release 150, 63 (2011).CrossRefGoogle Scholar
- 18.W.J. King, M.W. Toepke, and W.L. Murphy, Acta Biomater. 7, 975 (2011).CrossRefGoogle Scholar
- 19.D.L. Elbert, Acta Biomater. 7, 31 (2011).CrossRefGoogle Scholar
- 20.O. Franssen and W.E. Hennink, Int. J. Pharm. 168, 1 (1998).CrossRefGoogle Scholar
- 21.N.A. Impellitteri, M.W. Toepke, S.K.L. Levengood, and W.L. Murphy, Biomaterials 33, 3475 (2012).CrossRefGoogle Scholar
- 22.S. Kanyas, D. Aydin, R. Kizilel, A.L. Demirel, and S. Kizilel, PLoS ONE 9, e88125 (2014).CrossRefGoogle Scholar
- 23.W.J. King, N.J. Pytel, K. Ng, and W.L. Murphy, Macromol. Biosci. 10, 580 (2010).CrossRefGoogle Scholar
- 24.M. Dadsetan, K.E. Taylor, C. Yong, Ž. Bajzer, L. Lu, and M.J. Yaszemski, Acta Biomater. 9, 5438 (2013).CrossRefGoogle Scholar
- 25.S.J. Miller, Mathematics Department Brown University (2006), p. 1.Google Scholar
- 26.G. Socrates, Infrared and Raman Characteristic Group Frequencies: Tables and Charts (West Sussex, England: John Wiley & Sons, 2004), p. 71.Google Scholar
- 27.R.J. Stenekes, O. Franssen, E.M. van Bommel, D.J. Crommelin, and W.E. Hennink, Pharm. Res. 15, 557 (1998).CrossRefGoogle Scholar
- 28.O. Cevik, D. Gidon, and S. Kizilel, Acta Biomater. 11, 151 (2015).CrossRefGoogle Scholar
- 29.D. Gidon, D. Aydin, and S. Kizilel, Biomed. Mater. 10, 065001 (2015).CrossRefGoogle Scholar
- 30.P.F. Davies and S. Tripathi, Circ. Res. 72, 239 (1993).CrossRefGoogle Scholar