Division of BioTherapeutics, Leiden Academic Centre for Drug Research, Leiden, Netherlands.
Tyndall National Institute, University College Cork, Cork, Ireland.
Eur J Pharm Sci. 2020 Apr 15;146:105269. doi: 10.1016/j.ejps.2020.105269. Epub 2020 Feb 18.
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.
作为溶解微针（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，掺入疫苗抗原的免疫原性。本研究的目的是研究透明质酸（一种广泛用于制造 dMN 的聚合物）的分子量对微针在皮肤中溶解的时间以及在小鼠中的抗体反应和体外 T 细胞激活的影响。透明质酸分子量（HA-MW）不影响抗体反应（低于 150 kDa 时）或针对模型抗原卵清蛋白的 CD4+ T 细胞反应。然而，HA-MW 对 dMN 的制造有影响。1.8 MDa 的 HA 不适合制造 dMN。同样，4.8 kDa 的 HA 生成的 dMN 阵列不如其他 HA-MW 坚固，需要优化干燥条件。最后，较高的 HA-MW 导致 dMN 阵列的应用时间更长，以便将微针完全溶解到皮肤中。具体来说，我们确定 20 kDa 的 HA 是制造 dMN 的最佳 HA-MW，因为这种 MW 的 dMN 坚固且在皮肤中快速溶解，而不会影响免疫原性。
