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用于结肠靶向递送的叶酸修饰壳聚糖5-氟尿嘧啶纳米颗粒包埋海藻酸钙珠

Folate-Modified Chitosan 5-Flourouraci Nanoparticles-Embedded Calcium Alginate Beads for Colon Targeted Delivery.

作者信息

Ullah Shafi, Nawaz Asif, Farid Arshad, Latif Muhammad Shahid, Fareed Muhammad, Ghazanfar Shakira, Galanakis Charis M, Alamri Abdulhakeem S, Alhomrani Majid, Asdaq Syed Mohammed Basheeruddin

机构信息

Advanced Drug Delivery Lab, Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan 29050, Pakistan.

Gomal Center of Biochemistry and Biotechnology, Gomal University, Dera Ismail Khan 29050, Pakistan.

出版信息

Pharmaceutics. 2022 Jun 28;14(7):1366. doi: 10.3390/pharmaceutics14071366.

DOI:10.3390/pharmaceutics14071366
PMID:35890262
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9315928/
Abstract

Gel beads are formed when alginate acid reacts with divalent cations, particularly Ca. As a result of this feature, it is one of the best materials for making gel beads. Furthermore, it swells only slightly at acidic pH, resulting in stable alginate acid beads, but swells and dissolves rapidly at higher pH values, leading to pH-responsive release. Our current study aimed to embed folate-modified chitosan 5FU nanoparticles (FA-CS-5FU-NPs) into calcium alginate beads for colon-targeted delivery. Calcium alginate beads were developed successfully. Based on the method of drying, two types of beads were obtained: freeze-dried folate-modified chitosan 5FU nanoparticles-embedded beads (FA-CS-5FU-NP-Bf) and oven-dried folate-modified chitosan 5FU nanoparticles-embedded beads (FA-CS-5FU-NP-Bo). The size of (FA-CS-5FU-NP-Bf) was significantly larger than (FA-CS-5FU-NP-Bo). Swelling index (SI), erosion index (EI), and water-uptake index (WUI) of (FA-CS-5FU-NP-Bf) beads were significantly higher than FA-CS-5FU-NP-Bo beads at simulated intestinal pH. An insignificant difference was observed in the release rate of 5FU between (FA-CS-5FU-NP-Bf) and FA-CS-5FU-NP-Bo. The release rate of FA-CS-5FU-NPs was significantly higher than FA-CS-5FU-NP-Bf and FA-CS-5FU-NP-Bo. Pharmacokinetic parameters of 5FU solution, FA-CS-5FU-NPs, and FA-CS-5FU-NP-Bo were analyzed. Solution of pure 5FU showed significantly higher C and lower AUC, T, and Vd than both FA-CS-5FU-NPs and FA-CS-5FU-NPs-Bo, suggesting that FA-CS-5FU-NPs and FA-CS-5FU-NPs-Bo have sustained-release behavior. Biodistribution studies also show that maximum drug amounts were found in the colon from nanoparticles-embedded beads. FA-CS-5FU-NPs-Bo avoid releasing drugs in the stomach and small intestine and make them available in the colon region in higher concentrations to target the colon region specifically.

摘要

当海藻酸与二价阳离子，特别是钙离子反应时，会形成凝胶珠。由于这一特性，它是制备凝胶珠的最佳材料之一。此外，它在酸性pH值下仅轻微膨胀，从而形成稳定的海藻酸珠，但在较高pH值下会迅速膨胀并溶解，实现pH响应性释放。我们目前的研究旨在将叶酸修饰的壳聚糖5-氟尿嘧啶纳米颗粒（FA-CS-5FU-NPs）包埋到海藻酸钙珠中，用于结肠靶向递送。成功制备了海藻酸钙珠。根据干燥方法，获得了两种类型的珠子：冻干的叶酸修饰壳聚糖5-氟尿嘧啶纳米颗粒包埋珠（FA-CS-5FU-NP-Bf）和烘干的叶酸修饰壳聚糖5-氟尿嘧啶纳米颗粒包埋珠（FA-CS-5FU-NP-Bo）。（FA-CS-5FU-NP-Bf）的尺寸显著大于（FA-CS-5FU-NP-Bo）。在模拟肠道pH值下，（FA-CS-5FU-NP-Bf）珠的溶胀指数（SI）、侵蚀指数（EI）和吸水率指数（WUI）显著高于FA-CS-5FU-NP-Bo珠。（FA-CS-5FU-NP-Bf）和FA-CS-5FU-NP-Bo之间5-氟尿嘧啶的释放速率差异不显著。FA-CS-5FU-NPs的释放速率显著高于FA-CS-5FU-NP-Bf和FA-CS-5FU-NP-Bo。分析了5-氟尿嘧啶溶液、FA-CS-5FU-NPs和FA-CS-5FU-NP-Bo的药代动力学参数。纯5-氟尿嘧啶溶液的C显著高于FA-CS-5FU-NPs和FA-CS-5FU-NPs-Bo，而AUC、T和Vd则较低，这表明FA-CS-5FU-NPs和FA-CS-5FU-NPs-Bo具有缓释行为。生物分布研究还表明，在包埋纳米颗粒的珠子中，结肠中的药物含量最高。FA-CS-5FU-NP-Bo可避免药物在胃和小肠中释放，并使其在结肠区域以更高浓度存在，从而特异性地靶向结肠区域。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e1236cf64cb9/pharmaceutics-14-01366-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e617e9693b28/pharmaceutics-14-01366-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/063e56000c7c/pharmaceutics-14-01366-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/aa5aef806b6f/pharmaceutics-14-01366-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/0787aa7de530/pharmaceutics-14-01366-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/06ee988e54ba/pharmaceutics-14-01366-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e236038c3389/pharmaceutics-14-01366-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/d693890e5bf9/pharmaceutics-14-01366-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/544a8c66ee8a/pharmaceutics-14-01366-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e1236cf64cb9/pharmaceutics-14-01366-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e617e9693b28/pharmaceutics-14-01366-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/063e56000c7c/pharmaceutics-14-01366-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/aa5aef806b6f/pharmaceutics-14-01366-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/0787aa7de530/pharmaceutics-14-01366-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/06ee988e54ba/pharmaceutics-14-01366-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e236038c3389/pharmaceutics-14-01366-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/d693890e5bf9/pharmaceutics-14-01366-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/544a8c66ee8a/pharmaceutics-14-01366-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5c55/9315928/e1236cf64cb9/pharmaceutics-14-01366-g009.jpg

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本文引用的文献

[1]
5-Fluorouracil-Loaded Folic-Acid-Fabricated Chitosan Nanoparticles for Site-Targeted Drug Delivery Cargo.

Polymers (Basel). 2022-5-13

[2]
Single- versus Dual-Targeted Nanoparticles with Folic Acid and Biotin for Anticancer Drug Delivery.

Pharmaceutics. 2021-3-3

[3]
Folic acid decorated chitosan-coated solid lipid nanoparticles for the oral treatment of rheumatoid arthritis.

Ther Deliv. 2021-4

[4]
Alginate-C18 Conjugate Nanoparticles Loaded in Tripolyphosphate-Cross-Linked Chitosan-Oleic Acid Conjugate-Coated Calcium Alginate Beads as Oral Insulin Carrier.

Mol Pharm. 2018-7-24

[5]
Folic acid-modified liposomal drug delivery strategy for tumor targeting of 5-fluorouracil.

Eur J Pharm Sci. 2017-12-13

[6]
Guar gum oleate-graft-poly(methacrylic acid) hydrogel as a colon-specific controlled drug delivery carrier.

Carbohydr Polym. 2016-12-2

[7]
Doxorubicin-loaded fucoidan capped gold nanoparticles for drug delivery and photoacoustic imaging.

Int J Biol Macromol. 2016-10

[8]
A 5-fluorouracil-loaded floating gastroretentive hollow microsphere: development, pharmacokinetic in rabbits, and biodistribution in tumor-bearing mice.

Drug Des Devel Ther. 2016-3-3

[9]
In Vitro Investigation of Influences of Chitosan Nanoparticles on Fluorescein Permeation into Alveolar Macrophages.

Pharm Res. 2016-6

[10]
Mechanisms and biomaterials in pH-responsive tumour targeted drug delivery: A review.

Biomaterials. 2016-4

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