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. 2020 Jun 9;12(6):531.
doi: 10.3390/pharmaceutics12060531.

Characterization of Hepatitis B Surface Antigen Loaded Polylactic Acid-Based Microneedle and Its Dermal Safety Profile

Young-Guk Na  1 , Minki Kim  1 , Mingu Han  1 , Hyun Wook Huh  1 , Ji-Seok Kim  2 , Jong Chan Kim  2 , Jung-Hwan Park  2 , Hong-Ki Lee  1 , Cheong-Weon Cho  1
Affiliations

Characterization of Hepatitis B Surface Antigen Loaded Polylactic Acid-Based Microneedle and Its Dermal Safety Profile

Young-Guk Na et al. Pharmaceutics. .

Abstract

A surge of interest in microneedle (MN) vaccines as a novel vaccination system has emerged. Before the clinical application of MN vaccine, an assessment of potential biological risks to skin and quality control of MN must be performed. Therefore, the present study aims to evaluate the physicochemical properties of MN and to evaluate the histological changes and inflammatory cell infiltrations after the application of MN with hepatitis B surface antigen (HBsAg). During in vitro and in vivo release testing, HBsAg MN released over 70% of HBsAg at 30 min. During the pyrogen test of HBsAg MN in rabbit, no rabbit showed an individual rise in temperature of 0.5 °C or more. MN with HBsAg produced the moderate immunization in mice. MN application did not alter the thickness of dermal and epidermal layers in mice. In addition, the topical applications of MN and MN for hepatitis B vaccine did not acutely induce the inflammation, allergic reaction, dermal toxicity and skin irritation. Thus, the MN system for the delivery of HBsAg could be the promising technology in the hepatitis B vaccination.

Keywords: acute dermal toxicity; dermal safety; hepatitis B vaccine; microneedle; polylactic acid; skin irritation.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Images of (a) uncoated polylactic acid (PLA) microneedles and (b) coated microneedles with hepatitis B virus (HBV) surface antigen (HBsAg) formulation. Scale bar is 200 µm.
Figure 2
Figure 2
SEM images of blank microneedle (MN) (a) and HBsAg MN (b). Scale bar = 100 µm.
Figure 3
Figure 3
Diagram of lab made cutting device (Prof. Cho’s lab) (a) and SEM images of HBsAg MNs ((b)-a), MN section by cutting method ((b)-b and -c) and collected tip by cutter ((b)-d). Scale bar = 100 µm ((b)a, b and d). Scale bar = 20 µm ((b)c).
Figure 4
Figure 4
Optical micrograph of porcine skin pierced by an array of (a) uncoated MNs and (b) coated MNs subsequently exposed to Trypan Blue dye.
Figure 5
Figure 5
Comparison of HBsAg antigenicity in phosphate buffered saline (PBS) and on microneedles (MNs) at 25 °C and 40 °C after 2 months of storage. Data represented as average ± SD (n = 4).
Figure 6
Figure 6
In vitro release profile of HBsAg MN. Dashed line represents 90% of cumulative release (n = 3).
Figure 7
Figure 7
In vivo release profile of HBsAg MN after the application of HBsAg and blank MN (n = 3).
Figure 8
Figure 8
Serum HBsAg IgG level after the intradermal injection of HBsAg, application of blank and HBsAg MN (n = 4). Boost vaccination was carried out on day 14. Dashed line represents the marker of adequate immunity (> 10 mIU/mL).
Figure 9
Figure 9
SEM image of HBsAg MN after the application on mouse skin.
Figure 10
Figure 10
Representative hematoxylin and eosin (H&E) stain section of skin (a), the change of epidermal and dermal thickness (b), the score of inflammatory cell infiltration (c), and the infiltration or degradation of mast cells (d) after the application of needle (positive control), negative control and HBsAg MN, respectively. Scale bar = 500 µm.
Figure 11
Figure 11
Change of temperature after the application of HBsAg MN in rabbits. Grey shade represents the normal temperature of rabbit.
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