School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Belfast, BT9 7BL, UK.
Pharm Res. 2009 Nov;26(11):2513-22. doi: 10.1007/s11095-009-9967-2. Epub 2009 Sep 11.
In this study we determined, for the first time, the ability of microorganisms to traverse microneedle-induced holes using two different in vitro models.
When employing Silescol membranes, the numbers of Candida albicans, Pseudomonas aeruginosa and Staphylococcus epidermidis crossing the membranes were an order of magnitude lower when the membranes were punctured by microneedles rather than a 21G hypodermic needle. Apart from the movement of C. albicans across hypodermic needle-punctured membranes, where 40.2% of the microbial load on control membranes permeated the barrier over 24 h, the numbers of permeating microorganisms was less than 5% of the original microbial load on control membranes. Experiments employing excised porcine skin and radiolabelled microorganisms showed that the numbers of microorganisms penetrating skin beyond the stratum corneum were approximately an order of magnitude greater than the numbers crossing Silescol membranes in the corresponding experiments. Approximately 10(3) cfu of each microorganism adhered to hypodermic needles during insertion. The numbers of microorganisms adhering to MN arrays were an order of magnitude higher in each case.
We have shown here that microneedle puncture resulted in significantly less microbial penetration than did hypodermic needle puncture and that no microorganisms crossed the viable epidermis in microneedle-punctured skin, in contrast to needle-punctured skin. Given the antimicrobial properties of skin, it is, therefore, likely that application of microneedle arrays to skin in an appropriate manner would not cause either local or systemic infection in normal circumstances in immune-competent patients. In supporting widespread clinical use of microneedle-based delivery systems, appropriate animal studies are now needed to conclusively demonstrate this in vivo. Safety in patients will be enhanced by aseptic or sterile manufacture and by fabricating microneedles from self-disabling materials (e.g. dissolving or biodegradable polymers) to prevent inappropriate or accidental reuse.
本研究首次采用两种不同的体外模型，确定了微生物穿透微针诱导孔的能力。
当使用 Silescol 膜时，与通过微针穿刺相比，通过 21G 皮下针穿刺时，穿过膜的白色念珠菌、铜绿假单胞菌和表皮葡萄球菌的数量要低一个数量级。除了穿过皮下针穿刺膜的白色念珠菌的迁移外，在 24 小时内，对照膜上 40.2%的微生物负荷穿透了屏障，而穿透对照膜的微生物数量不到原始微生物负荷的 5%。使用离体猪皮和放射性标记微生物的实验表明，穿透角质层以外皮肤的微生物数量大约比相应实验中穿过 Silescol 膜的微生物数量高一个数量级。在插入过程中，每个微生物大约有 10(3)个菌落形成单位附着在皮下针上。在每种情况下，附着在 MN 阵列上的微生物数量都高出一个数量级。
我们在这里表明，与皮下针穿刺相比，微针穿刺导致的微生物渗透明显减少，并且与针穿刺皮肤不同，在微针穿刺皮肤中没有微生物穿透活表皮。鉴于皮肤的抗菌特性，因此，在免疫功能正常的患者中，以适当的方式将微针阵列应用于皮肤不太可能导致局部或全身感染。为了支持广泛的临床使用基于微针的给药系统，现在需要进行适当的动物研究，以在体内明确证明这一点。通过无菌或无菌制造以及使用自毁材料（例如可溶解或可生物降解的聚合物）制造微针，可以提高患者的安全性，以防止不当或意外重复使用。
