Volume 25 Issue 1 - October 11, 2013 PDF
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Fully Embeddable Chitosan Microneedles as a Sustained Release Depot for Intradermal Vaccination
Mei-Chin Chen*, Shih-Fang Huang, Kuan-Ying Lai and Ming-Hung Ling
Department of Chemical Engineering, National Cheng Kung University, Tainan, Taiwan (ROC)
 
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This study introduced a microneedle transdermal delivery system, composed of embeddable chitosan microneedles and a poly(L-lactide-co-D,L-lactide) (PLA) supporting array, for complete and sustained delivery of encapsulated antigens to the skin (Fig. a). Chitosan microneedles were mounted on the top of the strong PLA supporting array, which can provide mechanical strength to achieve full insertion of the microneedles into the skin(Fig. b). Upon insertion into rat skin in vivo, chitosan microneedles can successfully separate from the supporting array and be left within the skin for sustained drug delivery without wearing a transdermal patch(Fig. c and d). The penetration depth of microneedles was approximately 600 μm (Fig. e), which is beneficial for targeted delivery of antigens to antigen-presenting cells in the epidermis and dermis. To evaluate the utility of chitosan microneedles for intradermal vaccination, ovalbumin (OVA, MW = 44.3 kDa) was used as a model antigen (Fig. f). When the OVA-loaded microneedles were embedded within rat skin in vivo, histological examination showed that chitosan microneedles gradually degrade over time and achieve prolonged OVA exposure at the insertion sites for up to 14 days (Fig. g). Compared to traditional intramuscular immunization, rats immunized by a single microneedle dose of OVA elicited a significantly higher OVA-specific antibody response and lasted for at least 6 weeks (Fig. h). These results suggest that the embeddable chitosan microneedles can serve as a promising depot system for extended delivery of encapsulated antigens to provide sustained immune stimulation and improve immunogenicity.
Figure. Fully embeddable chitosan microneedles for sustained transdermal delivery of vaccines: (a) schematic illustrations of transdermal vaccine delivery using chitosan-PLA microneedle array; (b) Rhodamine 6G-loaded chitosan-PLA microneedle array; (c) microneedle array before and after skin insertion; (d) porcine cadaver skin after insertion of Rhodamine 6G-loaded microneedles; (e) histological sections of the porcine skin (left image) and the rat skin (right image) pierced by microneedles images of microneedles; (f) in vitro release profiles of ovalbumin (OVA)-loaded microneedles; (g) in vivo degradation of OVA-loaded microneedles; (h) OVA-specific IgG levels of rats after single dose of antigen.
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