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Biocompatible Coatings from Smart Biopolymer Nanoparticles for Enzymatically Induced Drug Release

GND
1033153710
Affiliation
Institut für Technische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany. ctolle1@aol.com.
Tolle, Christian;
Affiliation
Helmholtz-Zentrum für Infektionsforschung, Inhoffenstrasse 10, 38124 Braunschweig, Germany. jan.riedel@helmholtz-hzi.de.
Riedel, Jan;
Affiliation
Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. mikolai.carina@mh-hannover.de.
Mikolai, Carina;
Affiliation
Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. winkel.andreas@mh-hannover.de.
Winkel, Andreas;
Affiliation
Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. stiesch.meike@mh-hannover.de.
Stiesch, Meike;
Affiliation
Helmholtz-Zentrum für Infektionsforschung, Inhoffenstrasse 10, 38124 Braunschweig, Germany. dagmar.wirth@helmholtz-hzi.de.
Wirth, Dagmar;
ORCID
0000-0002-4915-7311
Affiliation
Institut für Technische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany. h.menzel@tu-bs.de.
Menzel, Henning

Nanoparticles can be used as a smart drug delivery system, when they release the drug only upon degradation by specific enzymes. A method to create such responsive materials is the formation of hydrogel nanoparticles, which have enzymatically degradable crosslinkers. Such hydrogel nanoparticles were prepared by ionotropic gelation sodium alginate with lysine-rich peptide sequences-either α-poly-L-lysine (PLL) or the aggrecanase-labile sequence KKKK-GRD-ARGSV↓NITEGE-DRG-KKKK. The nanoparticle suspensions obtained were analyzed by means of dynamic light scattering and nanoparticle tracking analysis. Degradation experiments carried out with the nanoparticles in suspension revealed enzyme-induced lability. Drugs present in the polymer solution during the ionotropic gelation can be encapsulated in the nanoparticles. Drug loading was investigated for interferon-β (IFN-β) as a model, using a bioluminescence assay with MX2Luc2 cells. The encapsulation efficiency for IFN-β was found to be approximately 25%. The nanoparticles suspension can be used to spray-coat titanium alloys (Ti-6Al-4V) as a common implant material. The coatings were proven by ellipsometry, reflection-absorption infrared spectroscopy, and X-ray photoelectron spectroscopy. An enzyme-responsive decrease in layer thickness is observed due to the degradation of the coatings. The Alg/peptide coatings were cytocompatible for human gingival fibroblasts (HGFIB), which was investigated by CellTiterBlue and lactate dehydrogenase (LDH) assay. However, HGFIBs showed poor adhesion and proliferation on the Alg/peptide coatings, but these could be improved by modification of the alginate with a RGD-peptide sequence. The smart drug release system presented can be further tailored to have the right release kinetics and cell adhesion properties.

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