Bile acid linked β-glucan nanoparticles for liver specific oral delivery of biologics

Chowdhury, A S M Raufur; Bai, Renu Geetha; Islam, Tamanna; Abir, Muhammad; Narayan, Mahesh; Khatun, Zehedina; Nurunnabi, Md

doi:10.1039/d2bm00316c

Cited by 9 publications

(5 citation statements)

References 41 publications

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“…Furthermore, YS can be constructed by conjugating β-glucans with other molecules to improve delivery, as performed by Chowdhury et al [ 49 ]. They synthesized a vehicle composed of taurocholic acid and β-glucan, capable of protecting molecules from the harmful environment of the stomach and accelerating the absorption of particles by the circulatory system, in addition to having target specificity for the liver, the organ of interest in the study.…”

Section: Characterization and Properties Of Yeast Shellsmentioning

confidence: 99%

Understanding yeast shells: structure, properties and applications

Silva de Macêdo,

Sousa de Pinho,

Duarte Silva

et al. 2024

ADMET DMPK

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Background and purpose: The employment of yeasts for biomedical purposes has become increasingly frequent for the delivery of prophylactic and therapeutic products. Its structural components, such as β-glucans, mannan, and chitin, can be explored as immunostimulators that show safety and low toxicity. Besides, this system minimizes antigen degradation after administration, facilitating the delivery to the target cells. Review approach: This review sought to present molecules derived from yeast, called yeast shells (YS), and their applications as carrier vehicles for drugs, proteins, and nucleic acids for immunotherapy purposes. Furthermore, due to the diversity of information regarding the production and immunostimulation of these compounds, a survey of the protocols and immune response profiles generated was presented. Key results: The use of YS has allowed the development of strategies that combine efficiency and effectiveness in antigen delivery. The capsular structure can be recognized and phagocytized by dendritic cells and macrophages. In addition, the combination with different molecules, such as nanoparticles or even additional adjuvants, improves the cargo loading, enhancing the system. Activation by specific immune pathways can also be achieved by different administration routes. Conclusion: Yeast derivatives combined in different ways can increase immunostimulation, enhancing the delivery of medicines and vaccine antigens. These aspects, combined with the simplicity of the production steps, make these strategies more accessible to be applied in the prevention and treatment of various diseases.

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Section: Characterization and Properties Of Yeast Shellsmentioning

confidence: 99%

Understanding yeast shells: structure, properties and applications

Silva de Macêdo,

Sousa de Pinho,

Duarte Silva

et al. 2024

ADMET DMPK

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“…Over the years, to overcome the limitations of the oral delivery of therapeutics, different approaches have been taken, and among them, a targeting-based drug delivery approach shows better effects. "It promotes the slow release of drug in the stomach, which subsequently extends the time available for drug dissolution and absorption in the stomach and/or small intestine [7,32,33]". However, there is still a lack of development of optimized formulations/vehicles that can be specifically delivered to the region of interest within the GI tract and exert their therapeutic effects for a longer duration [32].…”

Section: Introductionmentioning

confidence: 99%

β-Glucan and Fatty Acid Based Mucoadhesive Carrier for Gastrointestinal Tract Specific Local and Sustained Drug Delivery

et al. 2023

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The oral route is considered the most convenient route of drug administration for both systemic and local delivery. Besides stability and transportation, another unmet but important issue regarding oral medication is retention duration within the specific region of the gastrointestinal (GI) tract. We hypothesize that an oral vehicle that can adhere and maintain retention within the stomach for a longer duration can be more effective to treat stomach-related diseases. Therefore, in this project, we developed a carrier that is highly specific to the stomach and maintains its retention for a longer duration. We developed a vehicle composed of β-Glucan And Docosahexaenoic Acid (GADA) to observe its affinity and specificity to the stomach. GADA forms a spherical-shaped particle with negative zeta potential values that vary based on the feed ratio of docosahexaenoic acid. Docosahexaenoic acid is an omega-3 fatty acid that has transporters and receptors throughout the GI tract, such as CD36, plasma membrane-associated fatty acid-binding protein (FABP (pm)), and a family of fatty acid transport proteins (FATP1-6). The in vitro studies and characterization data showed that GADA has the capability to carry a payload of hydrophobic molecules and specifically deliver the payload to the GI tract, exert its therapeutic effects, and help to maintain stability for more than 12 h in the gastric and intestinal fluid. The particle size and surface plasmon resonance (SPR) data showed that GADA has a strong binding affinity with mucin in the presence of simulated gastric fluids. We observed a comparatively higher drug release of lidocaine in gastric juice than that in intestinal fluids, demonstrating the influence of the pH values of the media on drug-release kinetics. In vivo and ex vivo imaging of mice demonstrated that GADA maintains its retention within the stomach for at least 4 hr. This stomach-specific oral vehicle holds strong promise to translate various injectable therapeutic drugs to oral form upon further optimizations.

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“…We have previously reported that BG is very stable in acidic buffer, has a strong binding affinity with mucin, and forms microstructure particles in the presence of fatty acids . Studies show that the BG-based vehicle is highly effective in oral vaccine and protein delivery. , The BG-mediated mucoadhesive particle has the ability to protect therapeutic regimens from the harsh gastric environment, enhance retention of the therapeutic payload within the stomach for a longer duration, and maintain a sufficient therapeutic concentration for a prolonged period (6 h or more) . In addition, BG was found to act as an immune modulator of the gastrointestinal (GI) tract .…”

Section: Introductionmentioning

confidence: 99%

“…15,16 The BGmediated mucoadhesive particle has the ability to protect therapeutic regimens from the harsh gastric environment, enhance retention of the therapeutic payload within the stomach for a longer duration, and maintain a sufficient therapeutic concentration for a prolonged period (6 h or more). 17 In addition, BG was found to act as an immune modulator of the gastrointestinal (GI) tract. 18 Finally, BG has also shown significant potential in GI site-specific drug delivery to treat liver diseases, bowel disease, and stomach cancer.…”

Section: Introductionmentioning

confidence: 99%

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β-Glucan-Mediated Oral Codelivery of 5FU and Bcl2 siRNA Attenuates Stomach Cancer

Afrin,

Esquivel,

Kumar

et al. 2023

ACS Appl. Mater. Interfaces

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Based on cancer-related deaths, stomach cancer is ranked fifth, and first among Hispanics. Lack of technologies for early diagnosis and unavailability of targetspecific therapeutics are largely the causes of the poor therapeutic outcomes from existing chemotherapeutics. Currently available therapeutic modalities are invasive and require systemic delivery, although the cancer is localized in the stomach at its early stage. Therefore, we hypothesize that an oral local delivery approach can extend the retention duration of the therapeutics modalities within the stomach and thereby enhance therapeutic efficacy. To accomplish this, we have developed a ß-glucan (BG)-based oral delivery vehicle that can adhere to the mucus lining of the stomach for an extended period while controlling the release of Bcl2 siRNA and 5-fluorouracil (5FU) payload for over 6 h. We found that Bcl2 siRNA selectively knocked down the Bcl2 gene in a C57BL/6 stomach cancer mouse model followed by upregulation of apoptosis and remission of cancer. BG was found to be very effective in maintaining the stability of siRNA for at least 6 h, when submerged in simulated gastric juice tested in vitro. To investigate the potential therapeutic effects in vivo, we used a stomach cancer mouse model, where C57BL/6 mice were treated with 5FU, BG/5FU, siRNA, BG/siRNA, and BG/5FU/siRNA. Higher inhibition of Bcl2 and therapeutic efficacy were observed in mice treated with BG/5FU/siRNA confirmed with Western blotting and a TUNEL assay. Significant reduction in the tumor region was observed with histology (H&E) and immunohistochemistry (Ki67, TUNEL, and Bcl2) analyses. Overall, the oral formulation shows improved efficacy with nonsignificant side effects compared to the conventional treatment tested in the gastric cancer mouse model.

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Bile acid linked β-glucan nanoparticles for liver specific oral delivery of biologics

Abstract: Oral delivery remains one of the most convenient routes for drug administration compared to intravenous, intramuscular, and via suppositories. However, due to the risk of degradation, and proteolysis of molecules...

Cited by 9 publications

References 41 publications

Understanding yeast shells: structure, properties and applications

Understanding yeast shells: structure, properties and applications

β-Glucan and Fatty Acid Based Mucoadhesive Carrier for Gastrointestinal Tract Specific Local and Sustained Drug Delivery

β-Glucan-Mediated Oral Codelivery of 5FU and Bcl2 siRNA Attenuates Stomach Cancer

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