Department of BioNano Technology, Gachon BioNano Research Institute, Gachon University, Seongnam, Republic of Korea.
Science Department, International Vaccine Institute, Seoul, Republic of Korea.
Int J Pharm. 2020 Dec 15;591:119928. doi: 10.1016/j.ijpharm.2020.119928. Epub 2020 Oct 16.
In this study, dissolving microneedles (DMNs) with dual-release pattern, capable of both bolus release and slow release, were prepared. These DMNs were used with a hepatitis B vaccine that requires multiple shots to achieve immunological efficacy comparable to that obtained when two separate shots are administered. Dissolving microneedles with HBsAg in PLA tips and CMC coating formulation together (HBsAg-PLA/CMC-DMNs) consist of polylactic acid (PLA) tips for slow release, a carboxy-methyl cellulose (CMC) coating formulation for bolus release, and a dissolving base of polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP) for dissolution in the skin. The in vitro release pattern of HBsAg from the CMC coating formulation and PLA tips was observed. Through an in vivo test, 1) the delivery efficiency of HBsAg-PLA/CMC-DMNs was observed, and 2) the immunological efficacy of this method was compared with the efficacy of two shots delivered by conventional intramuscular (IM) administration and two shots delivered by HBsAg-coated microneedle (CMNs) administration. HBsAg-PLA/CMC-DMNs punctured the skin successfully. The PVA/PVP base was completely dissolved within 10 min of insertion, resulting in the delivery of all microneedle tips into the skin. In the in vitro release experiment, all of the HBsAg in the CMC coating formulation was released within 20 min, and the HBsAg present in the PLA tips was gradually released over more than 55 days. The antibody titer of one shot of HBsAg-PLA/CMC-DMNs was the same as or higher than two shots delivered by conventional IM and CMN methods. DMNs with dual-release pattern can deliver two formulations simultaneously with a single shot, resulting in improved immunological efficacy of HBsAg that requires multiple doses. In addition, this dual-release MN system can be used for the delivery of other drugs that require multiple administrations.
在这项研究中，制备了具有双重释放模式的溶解微针（DMN），能够实现突释和缓慢释放。这些 DMN 与乙型肝炎疫苗一起使用，该疫苗需要多次注射才能达到与两次单独注射相当的免疫效果。HBsAg-PLA/CMC-DMNs 由 PLA 尖端（用于缓慢释放）、CMC 涂层配方（用于突释）和 PVA/PVP 溶解基底（用于在皮肤中溶解）组成，其中 HBsAg 溶解在 PLA 尖端和 CMC 涂层配方中。观察了 CMC 涂层配方和 PLA 尖端中 HBsAg 的体外释放模式。通过体内试验，1）观察了 HBsAg-PLA/CMC-DMNs 的递送效率，2）将该方法的免疫效果与常规肌肉内（IM）给药的两针和 HBsAg 涂层微针（CMNs）给药的两针进行了比较。HBsAg-PLA/CMC-DMNs 成功刺穿皮肤。插入后 10 分钟内 PVA/PVP 基底完全溶解，导致所有微针尖端都递送到皮肤中。在体外释放实验中，CMC 涂层配方中的所有 HBsAg 在 20 分钟内释放完毕，而 PLA 尖端中的 HBsAg 则在 55 天以上逐渐释放。HBsAg-PLA/CMC-DMNs 一次注射的抗体滴度与常规 IM 和 CMN 方法的两针注射相同或更高。具有双重释放模式的 DMN 可以单次注射同时递送两种配方，从而提高需要多次剂量的 HBsAg 的免疫效果。此外，这种双重释放 MN 系统可用于递送需要多次给药的其他药物。
