Biomaterials used as matrix for dissolving micro needles (dMNs) may affect the manufacturing process as well as the potency of the active pharmaceutical ingredient, e.g. the immunogenicity of incorporated vaccine antigens. The aim of this study was to investigate the effect of the molecular weight of hyaluronan, a polymer widely used in the fabrication of dMNs, ranging in molecular weight from 4.8 kDa to 1.8 MDa, on the dissolution of microneedles in the skin in time as well as the antibody response in mice and T-cell activation in vitro. Hyaluronan molecular weight (HA-MWs) did not affect antibody responses (when lower than 150 kDa) nor CD4+ T-cell responses against model antigen ovalbumin. However, the HA-MWs had an effect on the fabrication of dMNs. The 1.8 MDa HA was not suitable for the fabrication of dMNs. Similarly, the 4.8 kDa HA generated dMN arrays less robust compared to the other HA-MWs requiring optimization of the drying conditions. Finally, higher HA-MWs led to longer application time of dMN arrays for a complete dissolution of microneedles into the skin. Specifically, we identified 20 kDa HA as the optimal HA-MW for the fabrication of dMNs as with this MW the dMNs are robust and dissolve fast in the skin without affecting immunogenicity.

中文翻译：

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透明质酸分子量：对溶解性微针在皮肤中的溶解时间和抗原免疫原性的影响。

用作溶解微针（dMN）的基质的生物材料可能会影响制造过程以及活性药物成分的效力，例如掺入的疫苗抗原的免疫原性。这项研究的目的是研究透明质酸的分子量，该透明质酸是一种广泛用于制造dMNs的聚合物，其分子量从4.8 kDa到1.8 MDa不等，也能及时溶解皮肤中的微针。作为小鼠中的抗体反应和体外T细胞活化。透明质酸分子量（HA-MWs）既不影响针对模型抗原卵清蛋白的抗体反应（低于150 kDa时），也不影响CD4 + T细胞反应。但是，HA-MW对dMN的制造有影响。1.8 MDa HA不适合制造dMN。同样，4。与其他需要优化干燥条件的HA-MW相比，8 kDa HA生成的dMN阵列的坚固性较差。最后，较高的HA-MW导致dMN阵列的应用时间更长，从而使微针完全溶解在皮肤中。具体来说，我们确定20 kDa HA是制造dMN的最佳HA-MW，因为具有这种MW，dMN坚固且可在皮肤中快速溶解而不影响免疫原性。