Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Department of Pharmaceutical Sciences, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Int J Pharm. 2019 Dec 15;572:118741. doi: 10.1016/j.ijpharm.2019.118741. Epub 2019 Nov 6.
Nanostructured lipid carriers (NLCs) can enhance the safe transdermal delivery system of drugs. Moreover, dissolving microneedles (MNs) can enhance the permeability and controlled drug release. In this study, NLCs were formulated as a suitable vehicle for aconitine (ACO) delivery to effectively inhibit the inflammation of fibroblast-like synoviocytes isolated from a rat model of adjuvant-induced arthritis (AA-FLS). To improve drug delivery, the ACO-loaded NLCs (ACO-NLCs) were embedded in polyvinylpyrrolidone-based dissolving MNs fabricated by an ultraviolet cross-linking method. The nanoparticles maintained good physical stability in the dissolving MNs. The insertion capabilities of the ACO-NLCs-MNs were determined by observing histological sections of the skin after insertion, and scanning electron microscopy was used to observe the changes in the MNs over time. In vivo microdialysis showed that the NLCs-MNs enhanced the transdermal delivery of ACO through disrupting the barrier function of the stratum corneum (SC) and releasing the drug continuously. The ACO-NLCs-MNs showed a significant inhibitory effect on the paw swelling and inflammation in AA model rats. Moreover, this dual approach involving NLCs-loaded dissolving MNs formed a drug reservoir and effectively improved the ACO-induced arrhythmia. These results indicate that NLCs-containing MNs could be promising systems for the effective transdermal delivery and controlled local administration of ACO.
纳米结构脂质载体 (NLCs) 可以增强药物的经皮传递系统的安全性。此外，溶解微针 (MNs) 可以增强通透性和控制药物释放。在这项研究中，NLCs 被制成一种合适的载体，用于将乌头碱 (ACO) 递送至佐剂诱导关节炎 (AA-FLS) 大鼠模型分离的成纤维样滑膜细胞，以有效抑制炎症。为了改善药物传递，将载有 ACO 的 NLCs (ACO-NLCs) 嵌入基于聚乙烯吡咯烷酮的溶解 MNs 中，通过紫外交联法制造。纳米颗粒在溶解 MNs 中保持良好的物理稳定性。通过观察插入后皮肤的组织学切片来确定 ACO-NLCs-MNs 的插入能力，并使用扫描电子显微镜观察 MNs 随时间的变化。体内微透析表明，NLCs-MNs 通过破坏角质层 (SC) 的屏障功能并持续释放药物来增强 ACO 的经皮传递。ACO-NLCs-MNs 对 AA 模型大鼠的爪肿胀和炎症具有显著的抑制作用。此外，这种包含 NLCs 的溶解 MNs 的双重方法形成了一个药物储库，有效改善了 ACO 引起的心律失常。这些结果表明，载有 NLCs 的 MNs 可能是一种有前途的系统，可以有效经皮传递和局部控制 ACO 的给药。
