Biocompatible Coatings from Smart Biopolymer Nanoparticles for Enzymatically Induced Drug Release

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2018-09, Vol.8 (4), p.103
• Main Authors: Tolle, Christian, Riedel, Jan, Mikolai, Carina, Winkel, Andreas, Stiesch, Meike, Wirth, Dagmar, Menzel, Henning
• Format: Article
• Language: English
• Subjects: alginate; Alginic acid; Bioluminescence; Biopolymers; Biopolymers - chemistry; Biopolymers - pharmacology; cell adherence; Cell adhesion; Chitosan - chemistry; Chitosan - pharmacology; Coated Materials, Biocompatible - chemistry; Coated Materials, Biocompatible - therapeutic use; Coatings; cyto-compatibility; Degradation; Drug delivery; Drug delivery systems; Drug Liberation; enzymatic cleavage; Enzymes; Fibroblasts; Fibroblasts - drug effects; Gelation; Humans; Hydrogel, Polyethylene Glycol Dimethacrylate - chemistry; Hydrogel, Polyethylene Glycol Dimethacrylate - pharmacology; Hydrogels; Infrared spectroscopy; Interferon-beta - chemistry; Interferon-beta - pharmacology; ionotropic gelation; L-Lactate dehydrogenase; Lability; Lactic acid; Light scattering; Lysine; Molecular weight; nanogel; Nanomaterials; Nanoparticles; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Particle size; Peptides; Photoelectron spectroscopy; Poly-L-lysine; Polylysine - chemistry; Polylysine - pharmacology; Proteins; reflection-absorption infrared spectroscopy; smart drug delivery; Sodium; Sodium alginate; Software; Spectrum analysis; Surface Properties; Titanium; Titanium - chemistry; Titanium alloys; Transplants & implants; X-ray photoelectron spectroscopy; β-Interferon
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom8040103

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.