Abstract
Intradermal delivery of antigens for vaccination is a very attractive approach since the skin provides a rich network of antigen presenting cells, which aid in stimulating an immune response. Numerous intradermal techniques have been developed to enhance penetration across the skin. However, these methods are invasive and/or affect the skin integrity. Hence, our group has devised zinc oxide (ZnO) nano-rods for non-destructive drug delivery. Chemical vapour deposition was used to fabricate aligned nano-rods on ZnO pre-coated silicon chips. The nano-rods’ length and diameter were found to depend on the temperature, time, quality of sputtered silicon chips, etc. Vertically aligned ZnO nano-rods with lengths of 30–35 µm and diameters of 200–300 nm were selected for in vitro human skin permeation studies using Franz cells with Albumin-fluorescein isothiocyanate (FITC) absorbed on the nano-rods. Fluorescence and confocal studies on the skin samples showed FITC penetration through the skin along the channels formed by the nano-rods. Bradford protein assay on the collected fluid samples indicated a significant quantity of Albumin-FITC in the first 12 h. Low antibody titres were observed with immunisation on Balb/c mice with ovalbumin (OVA) antigen coated on the nano-rod chips. Nonetheless, due to the reduced dimensions of the nano-rods, our device offers the additional advantage of excluding the simultaneous entrance of microbial pathogens. Taken together, these results showed that ZnO nano-rods hold the potential for a safe, non-invasive, and painless intradermal drug delivery.
Highlights
Efficient methods of drug delivery are of paramount importance in the successful treatment of medical conditions
Even if their role has been recently regarded as controversial [5], the presence of Langerhans cells immediately beneath the Stratum Corneum (SC) seems to promote an immunoactive effect: once stimulated by allergens, these cells actively migrate to the lymph nodes initiating immune responses
We demonstrated that chips with zinc oxide (ZnO) nano-rods facilitated the penetration of our vaccine prototype (Albumin) through the skin, while albumin only weakly stimulated an immune response, suggesting that the delivery of vaccine prototype from the chips requires further optimization
Summary
Efficient methods of drug delivery are of paramount importance in the successful treatment of medical conditions. Besides the traditional method of injection to deliver a certain drug molecule, there are a few non-invasive delivery routes (e.g., pulmonary, nasal, oral, transdermal), among which transdermal administration has the potential to determine a major impact on the way vaccines are administered. Advanced technologies have introduced formulations that make use of chemical as well as physical or mechanical penetration enhancers (e.g., iontophoresis and electroporation) or even small needles of different shapes. Regarding this last aspect, microneedles have been proven to be of great interest recently, since they are able to create little holes across the SC and facilitate the penetration of drug and vaccine molecules [3]. We utilized ovalbumin (OVA) as a vaccine prototype with the hope that the data obtained will be useful for future investigations of this novel device with regard to vaccines for pertussis, tetanus, influenza, etc
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