Mercaptonicotinic acid activated thiolated chitosan (MNA-TG-chitosan) to enable peptide oral delivery by opening cell tight junctions and enhancing transepithelial transport
Bibliographic record
Abstract
Recent advances in peptide delivery and nanotechnology has resulted in emergence of several non-parenteral administration routes that replace subcutaneous injections associated with patient discomfort. Thiolated biopolymers are relatively new materials being explored to enhance mucoadhesivity and permeability in these efforts, yet their pH dependent reactivity remains an obstacle. This work focussed on improving the mucoadhesivity of thiolated chitosans by activating them with mercaptonicotinic acid, in a bid to create a novel thiomerized chitosan that can open cell tight junctions for application in oral delivery. The synthesized mercaptonicotinic acid activated thiolated chistoan (MNA-TG-chitosan), along with thiolated chitosan (TG-chitosan) and unmodified chitosan were then used to create insulin nanoparticles (insNPs) using spray drying encapsulation process. Use of MNA-TG-chitosan in place of chitosan resulted in reduction of particle size of insNPs from 318 to 277 nm with no significant changes in polydispersity index (~ 0.2), encapsulation efficiency (~ 99%), insulin loading content (~ 25%) and morphology. Results from in-vitro cytotoxicity on TR146, CaCo2 and HepG2 cell lines revealed no significant effects on cell viability at 50-1000 μg/mL concentration. insNPs encapsulated with the new material, MNA-TG-chitosan, resulted in a 1.5-fold and 4.4-fold higher cellular uptake by HepG2 liver cells where insulin is metabolized, approximately 40% and 600% greater insulin transport through TR146 buccal cell monolayers, and 40% and 150% greater apparent permeability than insNPs encapsulated with unmodified chitosan and TG-chitosan respectively. The higher permeation achieved on using MNA-TG chitosan was attributed to the greater opening of the cell tight junction evidenced by reduction of transepithelial electrical resistance of TR146 buccal cell monolayers. This study demonstrates MNA-TG-chitosan as a promising material for improved peptide oral delivery.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 teacher head, 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".