Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 572, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijpharm.2019.118741
Keywords
Nanostructured lipid carriers; Dissolving microneedles; Aconitine; Controlled local administration; Anti-inflammatory; Cardiotoxicity
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Funding
- National Natural Science Foundation of China [81903810]
- Postdoctoral Science Foundation of China [2018M632156]
- Shanghai Sailing Program [18YF1423400]
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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.
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