In-situ Gelation of Sodium Alginate-chitosan for Oral Delivery of Probiotics

Abstract

We developed a new preparation to protect probiotic cells from adverse environmental conditions and improve their livability, which is called Lactobacillus casei-Sodium alginate-Chitosan (LSC). The LSC was prepared by mixing probiotics with sodium alginate-chitosan sol. The preparation contained complex calcium ions, which were released in the acidic environment of gastric juice, thus crosslinking to form in-situ gel. Different proportions of sodium alginate-chitosan were prepared to add to simulate gastrointestinal fluid to get the best ratio. The optimal ratio of LSC preparation was compared with traditional gel microspheres to observe the survival effect of probiotics in gastrointestinal fluid environment. Compared with sodium alginate sol, the porosity of sodium alginate-chitosan sol is lower, which is beneficial to the protection of probiotics. When the ratio of chitosan to sodium alginate is 1.5: 1.5 (w/v), the protective effect is the best. The protective ability of LSC is 64 times that of traditional microspheres, and it has the potential of synergistic anti-tumor. A probiotic preparation with simple preparation process and better protection effect compared with traditional microspheres was prepared, which has joint anti-tumor potential.

Keywords

sodium alginate / in-situ gelation / LSC / oral administration

References

[1] Asseri AH, Bakhsh T, Abuzahrah SS, et al. The Gut Dysbiosis-cancer Axis: Illuminating Novel Insights and Implications for Clinical Practice[J]. Frontiers in Pharmacology, 2023, 14: 1 208 044

[2] Meiqi W, Ge Y, Yuan T, et al. The Role of the Gut Microbiota in Gastric Cancer: The Immunoregulation and Immunotherapy[J]. Frontiers in Immunology, 2023, 14: 1 183 331

[3] Sommer F, Rühlemann MC, Bang C, et al. Microbiomarkers in Inflammatory Bowel Diseases: Caveats Come with Caviar[J]. Gut, 2017, 66(10.0): 1 734-1 738

[4] Shahverdi S, Barzegari AA, Bakhshayesh RV, et al. In-vitro and In-vivo Antibacterial Activity of Potential Probiotic Lactobacillus Paracasei Against Staphylococcus Aureus and Escherichia Coli[J]. Heliyon, 2023, 9(4): e14641

[5] Utz V E, Perdigón G, LeBlanc AdMd. Oral Administration of Milk Fermented by Lactobacillus Casei CRL431 was Able to Decrease Metastasis from Breast Cancer in a Murine Model by Modulating Immune Response Locally in the Lungs[J]. Journal of Functional Foods, 2019, 54: 263-270

[6] Laborda-Illanes A, Sanchez-Alcoholado L, Dominguez-Recio ME, et al. Breast and Gut Microbiota Action Mechanisms in Breast Cancer Pathogenesis and Treatment[J]. Cancers, 2020, 12(9): 2465

[7] Casas-Solís J, Huizar-López M, Irecta-Nájera CA, et al. Immunomodulatory Effect of Lactobacillus Casei in a Murine Model of Colon Carcinogenesis[J]. Probiotics and Antimicrobial Proteins, 2019, 12(3): 1 012-1 024

[8] Frakolaki G, Giannou V, Kekos D, et al. A Review of The Microencapsulation Techniques for The Incorporation of Probiotic Bacteria In Functional Foods[J]. Critical Reviews in Food Science and Nutrition, 2021, 61(9): 1-22

[9] Fu Y, Liu L, Zhang J, et al. Reinforcing Alginate Matrixes by Tea Polysaccharide Conjugates or Their Stabilized Nanoemulsion for Probiotics Encapsulation: Characterization, Survival after Gastrointestinal Digestion and Ambient Storage[J]. International Journal of Biological Macromolecules, 2023, 253: 126 828

[10] Hu X, Liu C, Zhang H, et al. In vitro Digestion of Sodium Alginate/Pectin Co-encapsulated Lactobacillus Bulgaricus and Its Application in Yogurt Bilayer Beads[J]. International Journal of Biological Macromolecules, 2021, 193: 1 050-1 058

[11] Arriaga-Morales JJ, Ordaz-Pichardo C, Castro-Muñoz R, et al. Attenuation of Hyperglycemia in Diabetic Rats Assisted by Immobilized Probiotic in Sodium Alginate[J]. Probiotics and Antimicrobial Proteins, 2023: 1–11

[12] Erdelyi L, Fenyvesi F, Gal B, et al. Investigation of the Role and Effectiveness of Chitosan Coating on Probiotic Microcapsules[J]. Polymers, 2022, 14(9): 1 664

[13] Khodaei D, Hamidi-Esfahani Z, Lacroix M. Gelatin and Low Methoxyl Pectin Films Containing Probiotics: Film Characterization and Cell Viability[J]. Food Bioscience, 2020, 36: 100 660

[14] Shi X, Xu S, Xu J, et al. Preparation and Properties of a Multi-cross-linked Chitosan/Sodium Alginate Composite Hydrogel[J]. Materials Letters, 2024, 354: 135 414

[15] Albarqi HA, Alqahtani AA, Ullah I, et al. Microwave-Assisted Physically Cross-Linked Chitosan-Sodium Alginate Hydrogel Membrane Doped with Curcumin as a Novel Wound Healing Platform[J]. AAPS Pharm. Sci. Tech., 2022, 23(2): 72

[16] Vázquez FR, Ovando AV, Reyes DM, et al. Use of Lactulose as Prebiotic and Chitosan Coating for Improvement the Viability of Lactobacillussp. FM4.C1.2 Microencapsulate with Alginate[J]. Processes, 2024, 12(1): 133

[17] Lin Q, Si Y, Zhou F, et al. Advances in Polysaccharides for Probiotic Delivery: Properties, Methods, and Applications[J]. Carbohydrate Polymers, 2024, 323: 121 414

[18] Ofer M, Ben B, Manel R, et al. Benefit of Oxaliplatin in Stage III Colon Cancer According to IDEA Risk Groups: Findings from the ACCENT Database of 4934 Patients[J]. Clinical Colorectal Cancer, 2021, 20(2): 130-136

[19] Fu X, Shi Y, Zang H, et al. Combination of Oxaliplatin and POM-1 by Nanoliposomes to Reprogram the Tumor Immune Microenvironment[J]. Journal of Controlled Release, 2022, 347: 1-13

[20] Fujii T, Kamishikiryo J, Morita T. Palbociclib Regulates Intracellular Lipids in Mammary Tumor Cells by Secreting Lipoprotein Lipase[J]. Pharmacological Reports, 2022, 74(3): 503-512

[21] Miyake M, Oda Y, Owari T, et al. Probiotics Enhances Anti-tumor Immune Response Induced by Gemcitabine Plus Cisplatin Chemotherapy for Urothelial Cancer[J]. Cancer Science, 2023, 114(3): 1 118-1 130

[22] Ren Z, Chen S, Lv H, et al. Effect of Bifidobacterium Animalis Subsp. Lactis SF on Enhancing the Tumor Suppression of Irinotecan by Regulating the Intestinal Flora[J]. Pharmacological Research, 2022, 184: 106 406

[23] He T, Wang L, Gou S, et al. Enhanced Immunogenic Cell Death and Antigen Presentation via Engineered Bifidobacterium bifidum to Boost Chemo-immunotherapy[J]. ACS Nano, 2023, 17(11): 9 953-9 971

[24] Danarto Y, Rochmadi, Budhijanto. Microencapsulation of Riboflavin (vitamin B₂) Using Alginate and Chitosan: Effect of Alginate and Chitosan Concentration Upon Encapsulation Efficiency[J]. IOP Conference Series: Materials Science and Engineering, 2020, 858(1): 012 030