Artificial cell microcapsule for oral delivery of live bacterial cells for therapy: design, preparation, and in-vitro characterization.
Bibliographic record
Abstract
PURPOSE: Bacterial cells can be engineered to synthesize a wide array of disease modifying substrates such as cytokines, vaccines and antibodies; however, their use as an orally delivered therapeutic is limited by poor gastrointestinal (GI) survival and instigation of immunogenic response. Artificial cell microcapsules have been well studied as a means to overcome such problems, however, presently obtainable microcapsules have limitations. This study summarizes a novel microcapsule design specifying its preparation and GI stability in-vitro. METHOD: Multilayer APPPA microcapsules were designed, prepared and characterized in-vitro for bacterial cell oral delivery using Lactobacillus reuteri cells as a model. Microcapsule structural integrity, mechanical stability, and GI survival studies were performed in simulated gastric (SGF) and intestinal (SIF) fluids in various pH conditions at 37.2 degrees C and compared with presently available alginate/poly-l-lysine/alginate (APA) microcapsules. HPLC was used for the microcapsule membrane permeability study. RESULTS: Results show that APPPA microcapsules can be prepared for bacterial cell encapsulation and are stable in simulated GI conditions. No microcapsule damage was reported when exposed to SGF and SIF for 12 hours at 250 rpm mechanical shaking at 37.2 degrees C. In addition, 93.2+/-2.3% and 98.9+/-0.6% of microcapsules were undamaged after 24 hours in SGF and SIF respectively. Microcapsule pH stability results show that 92.8+/-3.1% of microcapsules remained intact at pH 1, 3, 5, and 7 and no damage was observed at pH 9.0 when challenged for 24 hours. When exposed for 3 hours with 250 rpm shaking at 37.2 degrees C, no damage of the microcapsules in SGF and SIF at pH, 1,3,5,7, and 9 was observed. Compared to APA microcapsules, APPPA membranes showed superior GI stability and permeability for cell encapsulation. CONCLUSION: Novel APPPA microcapsules have superior features for oral delivery of live bacterial cells and they can be used for various clinical applications. However, further study such as membrane permeability, cytotoxicity, immune protection capacity, and suitability for live bacterial cell oral delivery in-vivo is required.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".