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叶酸接枝壳聚糖-海藻酸钠纳米胶囊作为用于递送姜黄油以治疗乳腺癌的有效靶向纳米载体

Folic Acid-Grafted Chitosan-Alginate Nanocapsules as Effective Targeted Nanocarriers for Delivery of Turmeric Oil for Breast Cancer Therapy.

作者信息

San Htet Htet Moe, Alcantara Khent Primo, Bulatao Bryan Paul I, Sorasitthiyanukarn Feuangthit Niyamissara, Nalinratana Nonthaneth, Suksamrarn Apichart, Vajragupta Opa, Rojsitthisak Pranee, Rojsitthisak Pornchai

机构信息

Center of Excellence in Natural Products for Ageing and Chronic Diseases, Chulalongkorn University, Bangkok 10330, Thailand.

Pharmaceutical Sciences and Technology Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand.

出版信息

Pharmaceutics. 2022 Dec 28;15(1):110. doi: 10.3390/pharmaceutics15010110.

DOI:10.3390/pharmaceutics15010110
PMID:36678739
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9862360/
Abstract

Folate receptors (FRs) highly expressed in breast cancers can be used as a recognized marker for preventing off-target delivery of chemotherapeutics. In this study, folic acid (FA)-grafted chitosan-alginate nanocapsules (CS-Alg-NCs) loaded with turmeric oil (TO) were developed for breast cancer targeting. CS was successfully conjugated with FA via an amide bond with a degree of substitution at 12.86%. The TO-loaded FA-grafted CS-Alg-NCs (TO-FA-CS-Alg-NCs) optimized by Box-Behnken design using response surface methodology had satisfactory characteristics with homogenous particle size (189 nm) and sufficient encapsulation efficiency and loading capacity (35.9% and 1.82%, respectively). In vitro release study of the optimized TO-FA-CS-Alg-NCs showed a sustained TO release following the Korsmeyer-Peppas model with a Fickian diffusion mechanism at pH 5.5 and 7.4. The TO-FA-CS-Alg-NCs showed lower IC than ungrafted TO-CS-Alg-NCs and unencapsulated TO against MDA-MB-231 and MCF-7 breast cancer cells, suggesting that FA-CS-Alg-NCs can improve anticancer activity of TO through its active targeting to the high FRs expressing breast cancers.

摘要

在乳腺癌中高表达的叶酸受体（FRs）可用作防止化疗药物脱靶递送的公认标志物。在本研究中，开发了负载姜黄油（TO）的叶酸（FA）接枝壳聚糖 - 海藻酸钠纳米胶囊（CS - Alg - NCs）用于乳腺癌靶向治疗。CS通过酰胺键成功与FA偶联，取代度为12.86%。采用响应面法通过Box - Behnken设计优化的负载TO的FA接枝CS - Alg - NCs（TO - FA - CS - Alg - NCs）具有令人满意的特性，粒径均匀（189 nm），包封率和载药量充足（分别为35.9%和1.82%）。优化后的TO - FA - CS - Alg - NCs的体外释放研究表明，在pH 5.5和7.4条件下，遵循Korsmeyer - Peppas模型且具有Fickian扩散机制，TO呈持续释放。与未接枝的TO - CS - Alg - NCs和未包封的TO相比，TO - FA - CS - Alg - NCs对MDA - MB - 231和MCF - 7乳腺癌细胞显示出更低的IC，表明FA - CS - Alg - NCs可通过其对高表达FRs的乳腺癌的主动靶向作用提高TO的抗癌活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/91844aa73a87/pharmaceutics-15-00110-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/33cbb396393f/pharmaceutics-15-00110-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/d68bfdac7ce3/pharmaceutics-15-00110-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/8779a55fa4f4/pharmaceutics-15-00110-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/ab99db0837b2/pharmaceutics-15-00110-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/f80d015fc002/pharmaceutics-15-00110-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/fbf977b581e1/pharmaceutics-15-00110-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/26cc5b64a88d/pharmaceutics-15-00110-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/8e63924ad82e/pharmaceutics-15-00110-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/91844aa73a87/pharmaceutics-15-00110-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/33cbb396393f/pharmaceutics-15-00110-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/d68bfdac7ce3/pharmaceutics-15-00110-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/8779a55fa4f4/pharmaceutics-15-00110-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/ab99db0837b2/pharmaceutics-15-00110-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/f80d015fc002/pharmaceutics-15-00110-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/fbf977b581e1/pharmaceutics-15-00110-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/26cc5b64a88d/pharmaceutics-15-00110-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/8e63924ad82e/pharmaceutics-15-00110-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a87/9862360/91844aa73a87/pharmaceutics-15-00110-g009.jpg

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[5]
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本文引用的文献

[1]
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Biomed Pharmacother. 2023-1

[2]
Targeting colon cancer stem cells using novel doublecortin like kinase 1 antibody functionalized folic acid conjugated hesperetin encapsulated chitosan nanoparticles.

Colloids Surf B Biointerfaces. 2022-9

[3]
Development of Turmeric Oil-Loaded Chitosan/Alginate Nanocapsules for Cytotoxicity Enhancement against Breast Cancer.

Polymers (Basel). 2022-4-29

[4]
In vitro evaluation of copper sulfide nanoparticles decorated with folic acid/chitosan as a novel pH-sensitive nanocarrier for the efficient controlled targeted delivery of cytarabine as an anticancer drug.

Biotechnol Appl Biochem. 2023-2

[5]
Bioadhesive chitosan nanoparticles: Dual targeting and pharmacokinetic aspects for advanced lung cancer treatment.

Carbohydr Polym. 2021-11-15

[6]
Folate receptor-mediated delivery of 1-MDT-loaded mesoporous silica magnetic nanoparticles to target breast cancer cells.

Nanomedicine (Lond). 2021-10

[7]
Design of experiments (DoE) to develop and to optimize nanoparticles as drug delivery systems.

Eur J Pharm Biopharm. 2021-8

[8]
Microwave-Assisted Extraction of L. Oil: Optimization, Chemical Structure and Composition, Antioxidant Activity and Comparison with Conventional Soxhlet Extraction.

Molecules. 2021-3-10

[9]
Chitosan Nanomedicine in Cancer Therapy: Targeted Delivery and Cellular Uptake.

Macromol Biosci. 2021-5

[10]
Folic acid-hydrophilic polymer coated mesoporous silica nanoparticles target doxorubicin delivery.

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