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用于皮内给药的载去铁胺纳米混悬液的溶蚀性微针

Deferasirox Nanosuspension Loaded Dissolving Microneedles for Intradermal Delivery.

作者信息

Faizi Hafsa Shahid, Vora Lalitkumar K, Nasiri Muhammad Iqbal, Wu Yu, Mishra Deepakkumar, Anjani Qonita Kurnia, Paredes Alejandro J, Thakur Raghu Raj Singh, Minhas Muhammad Usman, Donnelly Ryan F

机构信息

School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.

Department of Pharmaceutics, Hamdard Institute of Pharmaceutical Sciences, Hamdard University, Islamabad 45550, Pakistan.

出版信息

Pharmaceutics. 2022 Dec 15;14(12):2817. doi: 10.3390/pharmaceutics14122817.


DOI:10.3390/pharmaceutics14122817
PMID:36559310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9784557/
Abstract

Microneedles are minimally invasive systems that can deliver drugs intradermally without pain and bleeding and can advantageously replace the hypodermal needles and oral routes of delivery. Deferasirox (DFS) is an iron chelator employed in several ailments where iron overload plays an important role in disease manifestation. In this study, DFS was formulated into a nanosuspension (NSs) through wet media milling employing PVA as a stabilizer and successfully loaded in polymeric dissolving microneedles (DMNs). The release studies for DFS-NS clearly showed a threefold increased dissolution rate compared to pure DFS. The mechanical characterization of DFS-NS-DMNs revealed that the system was sufficiently strong for efficacious skin penetration. Optical coherence tomography images confirmed an insertion of up to 378 µm into full-thickness porcine skin layers. The skin deposition studies showed 60% drug deposition from NS-DMN, which was much higher than from the DFS-NS transdermal patch (DFS-NS-TP) (without needles) or pure DFS-DMNs. Moreover, DFS-NS without DMNs did not deposit well inside the skin, indicating that DMNs played an important role in effectively delivering drugs inside the skin. Therefore, it is evident from the findings that loading DFS-NS into novel DMN devices can effectively deliver DFS transdermally.

摘要

微针是一种微创系统,能够在无疼痛和出血的情况下将药物输送至真皮层,并且可以有效地替代皮下注射针头和口服给药途径。地拉罗司(DFS)是一种铁螯合剂,用于治疗多种铁过载在疾病表现中起重要作用的病症。在本研究中,通过以聚乙烯醇(PVA)作为稳定剂的湿介质研磨法将DFS制成纳米混悬液(NSs),并成功载入聚合物溶解微针(DMNs)中。DFS-NS的释放研究清楚地表明,与纯DFS相比,其溶解速率提高了三倍。DFS-NS-DMNs的力学特性表明,该系统强度足以有效穿透皮肤。光学相干断层扫描图像证实,其可插入全层猪皮肤达378 µm。皮肤沉积研究显示,NS-DMN的药物沉积率为60%,远高于DFS-NS透皮贴剂(DFS-NS-TP)(无针头)或纯DFS-DMNs。此外,不含DMNs的DFS-NS在皮肤内的沉积效果不佳,表明DMNs在有效将药物递送至皮肤内发挥了重要作用。因此,从研究结果可以明显看出,将DFS-NS载入新型DMN装置可有效经皮递送DFS。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/f142314232fa/pharmaceutics-14-02817-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/843d336dc493/pharmaceutics-14-02817-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/b4651b7395ee/pharmaceutics-14-02817-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/06d125071dc3/pharmaceutics-14-02817-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/99305df1a767/pharmaceutics-14-02817-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/8094ec7d8c0e/pharmaceutics-14-02817-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/deba0013e33b/pharmaceutics-14-02817-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/f142314232fa/pharmaceutics-14-02817-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/843d336dc493/pharmaceutics-14-02817-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/b4651b7395ee/pharmaceutics-14-02817-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/06d125071dc3/pharmaceutics-14-02817-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/99305df1a767/pharmaceutics-14-02817-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/8094ec7d8c0e/pharmaceutics-14-02817-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/deba0013e33b/pharmaceutics-14-02817-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f32d/9784557/f142314232fa/pharmaceutics-14-02817-g007.jpg

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本文引用的文献

[1]
Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy.

Pharm Res. 2023-7

[2]
Trilayer dissolving polymeric microneedle array loading Rose Bengal transfersomes as a novel adjuvant in early-stage cutaneous melanoma management.

Int J Pharm. 2022-11-5

[3]
Nanocrystals for controlled delivery: state of the art and approved drug products.

Expert Opin Drug Deliv. 2022-10

[4]
Nanosuspension-loaded dissolving bilayer microneedles for hydrophobic drug delivery to the posterior segment of the eye.

Biomater Adv. 2022-6

[5]
Beneath the Skin: A Review of Current Trends and Future Prospects of Transdermal Drug Delivery Systems.

Pharmaceutics. 2022-5-28

[6]
Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis.

J Control Release. 2022-8

[7]
Recent Advancements in Microneedle Technology for Multifaceted Biomedical Applications.

Pharmaceutics. 2022-5-20

[8]
Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes.

J Control Release. 2022-5

[9]
Stimuli-Responsive Microneedles as a Transdermal Drug Delivery System: A Demand-Supply Strategy.

Biomacromolecules. 2022-4-11

[10]
Nestorone nanosuspension-loaded dissolving microneedles array patch: A promising novel approach for "on-demand" hormonal female-controlled peritcoital contraception.

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