Oral nanotherapeutics based on Antheraea pernyi silk fibroin for synergistic treatment of ulcerative colitis

Ma, Yu; Duan, Lian; Sun, Jianfeng; Gou, Shuangquan; Chen, Fengyuan; Liang, Yuqi; Dai, Fangyin; Xiao, Bo

doi:10.1016/j.biomaterials.2022.121410

Cited by 73 publications

(37 citation statements)

References 61 publications

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“…On day 8, the mice were sacrificed by excessive anesthesia, and colons were acquired for macroscopic observation, gauge length, MPO activity, ELISA, and H&E staining analysis. In addition, the histological score was executed according to a previous report ( Ma et al, 2022 ). For the epithelium (E), the standards were as follows: 0, normal morphology; 1, loss of goblet cells; 2, loss of goblet cells in large areas; 3, loss of crypts; and 4, loss of crypts in large areas.…”

Section: Methodsmentioning

confidence: 99%

An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy

Wang

Guo

Liang

et al. 2022

Front. Bioeng. Biotechnol.

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Orally administered colon-targeted delivery vehicles are of major importance in the treatment of inflammatory bowel disease (IBD). However, it remains a challenge to maintain the integrity of such delivery vehicles during treatment, particularly in the gastric environment, which may cause untimely drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery system (OCDDS) based on acetylated konjac glucomannan (AceKGM) has been developed in this work, which accomplishes colonic localization release and targets local inflammatory macrophages. The AceKGM nanoparticle-loading curcumin (Cur) was successfully fabricated by emulsion solvent evaporation techniques. DLS, AFM, and SEM were used in order to evaluate the nanoparticles’ diameter as well as their in vitro drug release profile, and reactive oxygen species (ROS) scavenging results showed that the OCDDS considerably retained the activity of Cur treated with simulated gastric fluid (SGF) and controllably released in simulated intestinal fluid (SIF). In addition, the adhesion experiment results indicated that the nanoparticle could accumulate on the colonic macrophages. Evaluations in colitis mice showed that the treatment significantly alleviated the symptoms of colitis by decreasing the local level of myeloperoxidase (MPO) and the disease activity index (DAI) score in mice. In summary, the results of our research demonstrate that Cur–AceKGM nanoparticles exhibit significantly improved therapeutic efficacy compared to orally administered free Cur and can be developed as an effective drug delivery vehicle for IBD treatment.

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Section: Methodsmentioning

confidence: 99%

An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy

Wang

Guo

Liang

et al. 2022

Front. Bioeng. Biotechnol.

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“…Our constructed nanotherapeutics were embedded in a chitosan/alginate hydrogel, which could not only prevent their degradation in the upper GIT, but also release them in the colon lumen due to the specific disruption of the hydrogel therein. [62,63] The strongest near infrared (NIR) fluorescence signals in the colon were observed at 24 h and then gradually decreased (Figure 4h; Figure S15, Supporting Information), and NIR signals were only detected in the liver among the five major organs (Figure S16, Supporting Information). We further observed from the tissue section images that NMs were started to be internalized with partial epithelial cells in the healthy colon (green fluorescence) after 24 h of oral administration of hydrogel-embedding CS-ID@NMs, and US irradiation could slightly increase the quantities of NMs penetrating into the healthy colon tissues (Figure 4i-k).…”

Section: In Vivo Bio-safety and Bio-distribution Of Nmsmentioning

confidence: 99%

Oral Nanomotor‐Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo‐Sono‐Immunotherapy against Colon Cancer

Cao

Liu

et al. 2022

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The therapeutic outcomes of oral nanomedicines against colon cancer are heavily compromised by their lack of specific penetration into the internal tumor, favorable anti‐tumor activity, and activation of anti‐tumor immunity. Herein, hydrogen peroxide (H2O2)/ultrasound (US)‐driven mesoporous manganese oxide (MnOx)‐based nanomotors are constructed by loading mitochondrial sonosensitizers into their mesoporous channels and orderly dual‐functionalizing their surface with silk fibroin and chondroitin sulfate. The locomotory activities and tumor‐targeting capacities of the resultant nanomotors (CS‐ID@NMs) are greatly improved in the presence of H2O2 and US irradiation, inducing efficient mucus‐traversing and deep tumor penetration. The excess H2O2 in the tumor microenvironment (TME) is decomposed into hydroxyl radicals and oxygen by an Mn2+‐mediated Fenton‐like reaction, and the produced oxygen participates in sonodynamic therapy (SDT), yielding abundant singlet oxygen. The combined Mn2+‐mediated chemodynamic therapy and SDT cause effective ferropotosis of tumor cells and accelerate the release of tumor antigens. Importantly, animal experiments reveal that the treatment of combining oral hydrogel (chitosan/alginate)‐embedding CS‐ID@NMs and immune checkpoint inhibitors can simultaneously suppress the growth of primary and distal tumors through direct killing, reversion of immunosuppressive TME, and potentiation of systemic anti‐tumor immunity, demonstrating that the CS‐ID@NM‐based platform is a robust oral system for synergistic treatment of colon cancer.

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“…Similarly, there are several studies reporting the suitability of SFN as active vehicles for the transport and release of biomolecules targeting cancer cells [ 23 , 24 ] or to treat inflammatory conditions such as inflammatory bowel disease [ 25 , 26 , 27 , 28 ] and periodontitis [ 29 ]. However, the achievement of high drug loading content (DLC) becomes challenging due to the inherent nature of the biomolecules as well as the fibroin one.…”

Section: Introductionmentioning

confidence: 99%

Optimizing the Preparation of Silk Fibroin Nanoparticles and Their Loading with Polyphenols: Towards a More Efficient Anti-Inflammatory Effect on Macrophages

Ruiz–Alcaraz

Núñez‐Sánchez

Ruiz³

et al. 2023

Pharmaceutics

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Silk fibroin nanoparticles (SFN) have become a promising tool in drug delivery systems due to their physicochemical characteristics. SFN have shown their outstanding properties as an active vehicle for polyphenols, enhancing their antioxidant and anti-inflammatory effects on macrophages; therefore, it becomes necessary to have an easy, reproducible and scalable production method. In order to improve the production of nanoparticles, we performed direct precipitation of non-dialyzed silk fibroin solutions and evaluated the reproducibility of the method using dynamic light scattering. We also studied the loading efficiency of three different natural polyphenols using propylene glycol as a solvent. The loaded nanoparticles were fully characterized and used to treat human macrophage cells to assess the anti-inflammatory activity of these nanoparticles. The measured hydrodynamic characteristics of the SFN and the overall yield of the process showed that the new preparation method is highly reproducible and repeatable. Thus, we not only present a new scalable method to prepare silk nanoparticles but also how to improve the loading of natural polyphenolic compounds to the SFN, as well as the important anti-inflammatory effects of these loaded nanoparticles in a cell model of human macrophage cells.

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Oral nanotherapeutics based on Antheraea pernyi silk fibroin for synergistic treatment of ulcerative colitis

Cited by 73 publications

References 61 publications

An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy

An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy

Oral Nanomotor‐Enabled Mucus Traverse and Tumor Penetration for Targeted Chemo‐Sono‐Immunotherapy against Colon Cancer

Optimizing the Preparation of Silk Fibroin Nanoparticles and Their Loading with Polyphenols: Towards a More Efficient Anti-Inflammatory Effect on Macrophages

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