Bhowmik Mousam, A J Rajamma, S B Sateesha, R S Chandan, E K Girija, M Punith, Omar Ebna Azizal, R Rajesh
Department of Pharmaceutics, Acharya & BM Reddy College of Pharmacy, Bengaluru, 560107, India.
Department of Pharmacognosy, KLE College of Pharmacy, Bengaluru, 560010, India.
Biomed Microdevices. 2025 May 1;27(2):20. doi: 10.1007/s10544-025-00747-0.
This study demonstrates cyanocobalamin-loaded dissolving microneedles (CNBL-MNs) as a minimally invasive transdermal solution for managing cyanocobalamin (CNBL) deficiency, offering an alternative to intramuscular injections and oral supplements. The CNBL-MNs were developed using biodegradable, water-soluble polymers such as polyvinylpyrrolidone K25, Dextran K40, and chitosan to ensure controlled and gradual release of the CNBL. The formulation's stability and integrity were assessed through FTIR and XRD analyses. SEM imaging revealed well-formed microneedles with a height of 800 μm, a 200 μm base diameter, and a 500 μm pitch. EDS confirmed the successful incorporation of CNBL in the microneedle array. The Parafilm membrane insertion test revealed that the microneedles had strong mechanical properties and achieved 100% penetration efficiency. The microneedle array also demonstrated excellent (P > 0.05) flexibility and structural stability. Ex-vivo release studies showed that 88.51% of the CNBL was released over 48 h, following a first-order kinetic model. The n value of 0.51 for Korsmeyer-Peppas model indicate an anomalous transport mechanism, suggesting a combination of diffusion and erosion. The in-vivo pharmacokinetic evaluation in Wistar rats demonstrates that CNBL-MNs-2 exhibited a larger area under the curve (AUC₀-t) (61.57 ± 4.23 ng·h/mL) than the IP injection (37.04 ± 5.83 ng·h/mL), indicating significant (p > 0.05) increase in systemic availability and sustained release. The Cmax of CNBL-MNs-2 (6.10 ± 0.533 ng/mL) was comparable to that of the IP injection (6.20 ± 1.5 ng/mL), confirming efficient systemic absorption via the microneedle system. Additionally, Tmax was significantly (p > 0.05) prolonged with CNBL-MNs-2 (8 h) compared to the IP injection (2 h), suggesting a slower, more controlled CNBL release.
本研究证明，载有氰钴胺的可溶解微针（CNBL-MNs）是一种用于治疗氰钴胺（CNBL）缺乏症的微创透皮解决方案，为肌肉注射和口服补充剂提供了一种替代方法。CNBL-MNs是使用可生物降解的水溶性聚合物（如聚乙烯吡咯烷酮K25、葡聚糖K40和壳聚糖）开发的，以确保CNBL的可控和逐渐释放。通过傅里叶变换红外光谱（FTIR）和X射线衍射（XRD）分析评估了该制剂的稳定性和完整性。扫描电子显微镜（SEM）成像显示微针形态良好，高度为800μm，基部直径为200μm，间距为500μm。能谱分析（EDS）证实CNBL成功掺入微针阵列。Parafilm膜插入试验表明，微针具有很强的机械性能，穿透效率达到100%。微针阵列还表现出优异的（P > 0.05）柔韧性和结构稳定性。体外释放研究表明，按照一级动力学模型，48小时内88.51%的CNBL被释放。Korsmeyer-Peppas模型的n值为0.51，表明存在异常转运机制，提示扩散和侵蚀共同作用。在Wistar大鼠体内进行的药代动力学评估表明，CNBL-MNs-2的曲线下面积（AUC₀-t）（61.57 ± 4.23 ng·h/mL）大于腹腔注射组（37.04 ± 5.83 ng·h/mL），表明全身可用性显著（p > 0.05）增加且为持续释放。CNBL-MNs-2的Cmax（6.10 ± 0.533 ng/mL）与腹腔注射组（6.20 ± 1.5 ng/mL）相当，证实通过微针系统可实现有效的全身吸收。此外，与腹腔注射组（2小时）相比，CNBL-MNs-2的达峰时间（Tmax）显著（p > 0.05）延长（8小时），表明CNBL释放更缓慢、更可控。
