Nanolayered chemical modification of silicon surfaces with ionizable surface groups for pH-triggered protein adsorption and release: application to microneedles

Abstract

The aim of this work was to develop a nanolayered pH sensitive coating method whereby proteins are coated at a suitable pH on the surface of chemically modified biomedical/bioanalytical microdevices and protein release is triggered by a pH-shift upon contact with the physiological environment. In this work such a coating was developed and was applied onto microneedles. First, the surface of microneedle arrays was modified with basic groups with a surface pK a below physiological pH. This modification was a multistep procedure: first the surface was hydroxylated in a piranha mixture, then 3-aminopropyltriethoxysilane was coupled (yielding a "pH independent" surface with a positive charge over a broad pH range), next 4-pyridinecarboxaldehyde was coupled to the obtained surface amine groups and finally the imine bond was reduced by sodium cyanoborohydride. The obtained pH-sensitive pyridinemodified microneedles were coated with ovalbumin at surface pK a > pH > pI of the protein; thus the surface of the microneedles is positively charged and the protein is negatively charged. The coating efficiency of ovalbumin was 95% for the amine-modified (pH independent) and the pyridine-modified (pH sensitive) surfaces, whereas a non-modified surface had a coating efficiency of only 2%. After the protein-coated microneedle arrays were pierced into the skin, having a pH > surface pK a of the microneedle arrays, 70% of the protein was released within 1 minute, whereas the protein release from pH independent microneedle arrays was only 5%. In conclusion, we developed a procedure to efficiently coat microneedle arrays with proteins that are released upon piercing into human skin.

Mesoporous Silica Nanoparticle-Coated Microneedle Arrays for Intradermal Antigen Delivery

“…First, the pH-sensitive pyridine-modified microneedle arrays were prepared as described previously (6). The microneedle arrays were coated with LB-MSN-OVA at pH 5.8 in an EDTA buffer (1 mM).…”

Skin permeabilization for transdermal drug delivery: recent advances and future prospects

“…Additionally, the kinetics of insulin delivery to mice from dissolving MNs has also been shown to be comparable to subcutaneous injection [42]. Addressing the issue of what can be coated onto MNs, other studies have examined coating formulations to deliver the model proteins bovine pancreatic ribonuclease A (13.7 kDa) and chicken ovalbumin (45 kDa) [72], [73]. Both studies found that the model proteins could be delivered into skin in vitro , with dosage and release kinetics dependent on the coating chemistry.…”

Bioresponsive transcutaneous patches

“…pH-sensitive surface modification was also reported in the fabrication of pH-sensitive microneedles. Here, MNs were coated with ovalbumin, a model antigen, and a pH-sensitive pyridine surface [24]. Upon insertion into the acidic skin conditions, reduced electrostatic interactions allowed the ovalbumin to be efficiently released.…”