4.6 Article

Engineering of tetanus toxoid-loaded polymeric microneedle patches

期刊

DRUG DELIVERY AND TRANSLATIONAL RESEARCH
卷 13, 期 3, 页码 852-861

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SPRINGER HEIDELBERG
DOI: 10.1007/s13346-022-01249-9

关键词

Tetanus toxoid vaccine; Microneedles; Polyvinyl pyrrolidone; Carboxymethyl cellulose; Bicinchoninic acid assay; Immunization; Flow cytometry; Interferon gamma; Immunoglobulin G

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This study successfully fabricated tetanus toxoid laden microneedle patches using a polymeric blend and sorbitol as a plasticizer. The patches showed uniform thickness, folding endurance, and swelling profile. In vitro and in vivo experiments demonstrated the effectiveness of these patches in delivering the vaccine and inducing immune responses.
This study is aimed to fabricate tetanus toxoid laden microneedle patches by using a polymeric blend comprising of polyvinyl pyrrolidone and sodium carboxymethyl cellulose as base materials and sorbitol as a plasticizer. The tetanus toxoid was mixed with polymeric blend and patches were prepared by using vacuum micromolding technique. Microneedle patches were evaluated for physical attributes such as uniformity of thickness, folding endurance, and swelling profile. Morphological features were assessed by optical and scanning electron microscopy. In vitro performance of fabricated patches was studied by using bicinchoninic acid assay (BCA). Insertion ability of microstructures was studied in vitro on model skin parafilm and in vivo in albino rat. In vivo immunogenic activity of the formulation was assessed by recording immunoglobulin G (IgG) levels, interferon gamma (IFN-gamma) levels, and T-cell (CD4(+) and CD8(+)) count following the application of dosage forms. Prepared patches, displaying sharp-tipped and smooth-surfaced microstructures, remained intact after 350 +/- 36 foldings. Optimized microneedle patch formulation showed similar to 74% swelling and similar to 85.6% vaccine release within an hour. The microneedles successfully pierced parafilm. Histological examination of microneedle-treated rat skin confirmed disruption of epidermis without damaging the underneath vasculature. A significant increase in IgG levels (similar to 21%), IFN-gamma levels (similar to 30%), CD4(+) (similar to 41.5%), and CD8(+) (similar to 48.5%) cell count was observed in tetanus vaccine-loaded microneedle patches treated albino rats with respect to control (untreated) group at 42nd day of immunization. In conclusion, tetanus toxoid-loaded microneedle patches can be considered as an efficient choice for transdermal delivery of vaccine without inducing pain commonly experienced with hypodermic needles.

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