pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG
Abstract The gut microbiome is closely linked to gastrointestinal health and disease status. Oral administration of known probiotic strains is now considered a promising therapeutic strategy, especially for refractory diseases such as inflammatory bowel disease. In this study, we developed a nanostr...
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| Format: | Article |
| Language: | English |
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Wiley
2023-05-01
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| Series: | Bioengineering & Translational Medicine |
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| Online Access: | https://doi.org/10.1002/btm2.10527 |
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| author | Jihyun Kim Shwe Phyu Hlaing Juho Lee Dongmin Kwak Hyunwoo Kim Aruzhan Saparbayeva In‐Soo Yoon Eunok Im Yunjin Jung Jin‐Wook Yoo |
| author_facet | Jihyun Kim Shwe Phyu Hlaing Juho Lee Dongmin Kwak Hyunwoo Kim Aruzhan Saparbayeva In‐Soo Yoon Eunok Im Yunjin Jung Jin‐Wook Yoo |
| author_sort | Jihyun Kim |
| collection | DOAJ |
| description | Abstract The gut microbiome is closely linked to gastrointestinal health and disease status. Oral administration of known probiotic strains is now considered a promising therapeutic strategy, especially for refractory diseases such as inflammatory bowel disease. In this study, we developed a nanostructured hydroxyapatite/alginate (HAp/Alg) composite hydrogel that protects its encapsulated probiotic Lactobacillus rhamnosus GG (LGG) by neutralizing hydrogen ions that penetrate the hydrogel in a stomach without inhibiting LGG release in an intestine. Surface and transection analyses of the hydrogel revealed characteristic patterns of crystallization and composite‐layer formation. TEM revealed the dispersal of the nanosized HAp crystals and encapsulated LGG in the Alg hydrogel networks. The HAp/Alg composite hydrogel maintained its internal microenvironmental pH, thereby enabling the LGG to survive for substantially longer. At intestinal pH, the encapsulated LGG was completely released upon disintegration of the composite hydrogel. In a dextran sulfate sodium‐induced colitis mouse model, we then assessed the therapeutic effect of the LGG‐encapsulating hydrogel. This achieved intestinal delivery of LGG with minimal loss of enzymatic function and viability, ameliorating colitis by reducing epithelial damage, submucosal edema, inflammatory cell infiltration, and the number of goblet cells. These findings reveal the HAp/Alg composite hydrogel as a promising intestinal‐delivery platform for live microorganisms including probiotics and live biotherapeutic products. |
| first_indexed | 2024-03-13T10:52:26Z |
| format | Article |
| id | doaj.art-89fa2651cb6e4200b8bc42cf97bf1c0c |
| institution | Directory Open Access Journal |
| issn | 2380-6761 |
| language | English |
| last_indexed | 2024-03-13T10:52:26Z |
| publishDate | 2023-05-01 |
| publisher | Wiley |
| record_format | Article |
| series | Bioengineering & Translational Medicine |
| spelling | doaj.art-89fa2651cb6e4200b8bc42cf97bf1c0c2023-05-17T07:33:12ZengWileyBioengineering & Translational Medicine2380-67612023-05-0183n/an/a10.1002/btm2.10527pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GGJihyun Kim0Shwe Phyu Hlaing1Juho Lee2Dongmin Kwak3Hyunwoo Kim4Aruzhan Saparbayeva5In‐Soo Yoon6Eunok Im7Yunjin Jung8Jin‐Wook Yoo9College of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaCollege of Pharmacy and Research Institute for Drug Development Pusan National University Busan South KoreaAbstract The gut microbiome is closely linked to gastrointestinal health and disease status. Oral administration of known probiotic strains is now considered a promising therapeutic strategy, especially for refractory diseases such as inflammatory bowel disease. In this study, we developed a nanostructured hydroxyapatite/alginate (HAp/Alg) composite hydrogel that protects its encapsulated probiotic Lactobacillus rhamnosus GG (LGG) by neutralizing hydrogen ions that penetrate the hydrogel in a stomach without inhibiting LGG release in an intestine. Surface and transection analyses of the hydrogel revealed characteristic patterns of crystallization and composite‐layer formation. TEM revealed the dispersal of the nanosized HAp crystals and encapsulated LGG in the Alg hydrogel networks. The HAp/Alg composite hydrogel maintained its internal microenvironmental pH, thereby enabling the LGG to survive for substantially longer. At intestinal pH, the encapsulated LGG was completely released upon disintegration of the composite hydrogel. In a dextran sulfate sodium‐induced colitis mouse model, we then assessed the therapeutic effect of the LGG‐encapsulating hydrogel. This achieved intestinal delivery of LGG with minimal loss of enzymatic function and viability, ameliorating colitis by reducing epithelial damage, submucosal edema, inflammatory cell infiltration, and the number of goblet cells. These findings reveal the HAp/Alg composite hydrogel as a promising intestinal‐delivery platform for live microorganisms including probiotics and live biotherapeutic products.https://doi.org/10.1002/btm2.10527alginatecomposite hydrogelgastric pH resistancehydroxyapatiteintestinal deliveryprobiotics |
| spellingShingle | Jihyun Kim Shwe Phyu Hlaing Juho Lee Dongmin Kwak Hyunwoo Kim Aruzhan Saparbayeva In‐Soo Yoon Eunok Im Yunjin Jung Jin‐Wook Yoo pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG Bioengineering & Translational Medicine alginate composite hydrogel gastric pH resistance hydroxyapatite intestinal delivery probiotics |
| title | pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG |
| title_full | pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG |
| title_fullStr | pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG |
| title_full_unstemmed | pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG |
| title_short | pH‐sustaining nanostructured hydroxyapatite/alginate composite hydrogel for gastric protection and intestinal release of Lactobacillus rhamnosus GG |
| title_sort | ph sustaining nanostructured hydroxyapatite alginate composite hydrogel for gastric protection and intestinal release of lactobacillus rhamnosus gg |
| topic | alginate composite hydrogel gastric pH resistance hydroxyapatite intestinal delivery probiotics |
| url | https://doi.org/10.1002/btm2.10527 |
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