Abstract
Environmentally sensitive poly(N-isopropylacrylamide) (PNIPAAm) nanofibrous scaffolds loaded with a hydrophilic drug were fabricated via an electrospinning process. First, thermally crosslinkable poly(NIPAAm-co-N-methylolacrylamide) (PNN) was synthesized by redox polymerization below the phase transition temperature of PNIPAAm. The phase transition temperature of the PNN copolymer could be altered from 34 to 40 °C by changing the ratio of N-methylolacrylamide (NMA) to NIPAAm. Subsequently, PNN/chitosan nanofibers were electrospun using ethanol/acetic acid/water as a cosolvent. The PNN/chitosan nanofibers were sensitive to both pH and temperature. The fibrous structure of the soaked PNN/chitosan nanofibers was successfully preserved by the crosslinking of NMA. Furthermore, the chitosan-based nanoparticles (NPs) were introduced into the PNN nanofibers (PNN/NPs) to achieve prolonged drug release. The nanoparticles were observed in the PNN nanofibers by transmission electron microscopy. All of the scaffolds examined had high tensile strengths (1.45 MPa or above) and exhibited no significant cytotoxicity toward human fetal skin fibroblasts. Finally, doxycycline hyclate was used as a model drug. The results illustrated that PNN/NPs nanofibrous scaffolds exhibited continuous drug release behavior for up to 1 week, depending on the pH and temperature.
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References
Binkert T, Oberreich J, Meewes M, Nyffenegger R, Ricka J (1991) Coil-globule transition of poly(N-isopropylacrylamide): a study of segment mobility by fluorescence depolarization. Macromolecules 24(21):5806–5810
Caruso F, Caruso RA, Mohwald H (1998) Nanoengineering of inorganic and hybrid hollow spheres by colloidal templating. Science 282(5391):1111–1114
Hartgerink JD, Beniash E, Stupp SI (2002) Peptide-amphiphile nanofibers: a versatile scaffold for the preparation of self-assembling materials. Proc Natl Acad Sci USA 99(8):5133–5138
Huang C-H, Wang C-F, Don T-M, Chiu W-Y (2013) Preparation of pH- and thermo-sensitive chitosan-PNIPAAm core–shell nanoparticles and evaluation as drug carriers. Cellulose 20(4):1791–1805
Hulteen JC, Chen HX, Chambliss CK, Martin CR (1997) Template synthesis of carbon nanotubule and nanofiber arrays. Nanostruct Mater 9(1–8):133–136
Jayaraman K, Kotaki M, Zhang Y, Mo X, Ramakrishna S (2004) Recent advances in polymer nanofibers. J Nanosci Nanotechnol 4(1–2):52–65
Jeong SI, Krebs MD, Bonino CA, Samorezov JE, Khan SA, Alsberg E (2011) Electrospun chitosan-alginate nanofibers with in situ polyelectrolyte complexation for use as tissue engineering scaffolds. Tissue Eng Part A 17(1–2):59–70
Katti DS, Robinson KW, Ko FK, Laurencin CT (2004) Bioresorbable nanofiber-based systems for wound healing and drug delivery: optimization of fabrication parameters. J Biomed Mater Res B Appl Biomater 70(2):286–296
Kolambkar YM, Dupont KM, Boerckel JD, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE (2011) An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects. Biomaterials 32(1):65–74
Lee C-F, Lin C-C, Chi W-Y (2008) Thermosensitive and control release behavior of poly (N-isopropylacrylamide-co-acrylic acid) latex particles. J Polym Sci Part A Polym Chem 46(17):5734–5741
Lee WY, Cheng WY, Yeh YC, Lai CH, Hwang SM, Hsiao CW, Huang CW, Chen MC, Sung HW (2011) Magnetically directed self-assembly of electrospun superparamagnetic fibrous bundles to form three-dimensional tissues with a highly ordered architecture. Tissue Eng Part C Methods 17(6):651–661
Li WJ, Tuli R, Okafor C, Derfoul A, Danielson KG, Hall DJ, Tuan RS (2005) A three-dimensional nanofibrous scaffold for cartilage tissue engineering using human mesenchymal stem cells. Biomaterials 26(6):599–609
Liu W, Yeh Y-C, Lipner J, Xie J, Sung H-W, Thomopoulos S, Xia Y (2011) Enhancing the stiffness of electrospun nanofiber scaffolds with a controlled surface coating and mineralization. Langmuir 27(15):9088–9093
Ma PX, Zhang R (1999) Synthetic nano-scale fibrous extracellular matrix. J Biomed Mater Res 46(1):60–72
Piryaei A, Valojerdi MR, Shahsavani M, Baharvand H (2011) Differentiation of bone marrow-derived mesenchymal stem cells into hepatocyte-like cells on nanofibers and their transplantation into a carbon tetrachloride-induced liver fibrosis model. Stem Cell Rev Rep 7(1):103–118
Reneker DH, Yarin AL (2008) Electrospinning jets and polymer nanofibers. Polymer 49(10):2387–2425
Rinaudo M, Pavlov G, Desbrieres J (1999) Influence of acetic acid concentration on the solubilization of chitosan. Polymer 40(25):7029–7032
Sahoo S, Ang LT, Goh JC-H, Toh S-L (2010) Growth factor delivery through electrospun nanofibers in scaffolds for tissue engineering applications. J Biomed Mater Res A 93A(4):1539–1550
Schild HG (1992) Poly(N-isopropylacrylamide): experiment, theory and application. Prog Polym Sci 17(2):163–249
Sencadas V, Correia DM, Ribeiro C, Moreira S, Botelho G, Gomez Ribelles JL, Lanceros-Mendez S (2012) Physical-chemical properties of cross-linked chitosan electrospun fiber mats. Polym Test 31(8):1062–1069
Sill TJ, von Recum HA (2008) Electrospinning: applications in drug delivery and tissue engineering. Biomaterials 29(13):1989–2006
Song JH, Kim HE, Kim HW (2008) Production of electrospun gelatin nanofiber by water-based co-solvent approach. J Mater Sci Mater Med 19(1):95–102
Zhang Y, Yarin AL (2009) Stimuli-responsive copolymers of n-isopropyl acrylamide with enhanced longevity in water for micro- and nanofluidics, drug delivery and non-woven applications. J Mater Chem 19(27):4732–4739
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Huang, CH., Kuo, TY., Lee, CF. et al. Preparation of a thermo- and pH-sensitive nanofibrous scaffold with embedded chitosan-based nanoparticles and its evaluation as a drug carrier. Cellulose 21, 2497–2509 (2014). https://doi.org/10.1007/s10570-014-0290-7
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DOI: https://doi.org/10.1007/s10570-014-0290-7