Biocompatible Coatings from Smart Biopolymer Nanoparticles for Enzymatically Induced Drug Release

Abstract

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.

Chitosan–Azide Nanoparticle Coating as a Degradation Barrier in Multilayered Polyelectrolyte Drug Delivery Systems

“…This increase in particle size was an indication that the nanoparticles lost stability and larger aggregates are formed. Such a behaviour has been observed before upon degradation of the CS–TPP nanoparticles [34] and can be explained by a different ratio of TPP to Chitosan upon degradation of the chitosan. It had been shown before that the ratio of Chitosan to TPP strongly influenced the size of the particles and that there is a minimum particle size [35].…”

Neutrophils exhibit an individual response to different oral bacterial biofilms

“…For SEM, the cells were fixed with 0.1% glutaraldehyde and 4% PFA diluted in 200 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid). The samples were dried and sputtered as previously described [ 54 ] and analyzed by SEM (Crossbeam 540, Zeiss). Both techniques allowed the qualitative observation of NETs.…”

Sustained in vitro interferon-beta release and in vivo toxicity of PLGA and PEG-PLGA nanoparticles

“…10 Alginate hydrogels prepared by ionotropic gelation with poly-Llysine have been investigated as enzymatically degradable stimuli responsive carriers for IFN-b as model drug. 11 Differently from microencapsulation, PEGylation of IFNb can also prolong the drug blood life-time. [12][13][14] The pharmacokinetics of recombinant human IFN-b-1a in rats was examined, 5 and unmodied protein represented a half-life of 1 h following intravenous administration, while PEGylated IFN-b-1a suffered much slower elimination half-life (13 h).…”