Distinct morphological and internal state of irinotecan in liposomal structures: implications on irinotecan liposomal drug delivery
Bibliographic record
Abstract
Liposomes with unique internal states and morphology have profound implications for controlled drug delivery. This article demonstrates that the final morphology (oblong vs. spherical) and internal state of irinotecan as irinotecan-SucroseOctaSulfate(SOS) complex (gelled vs. precipitated) are impacted by the physical state (solid powder vs. liquid solution) of the used drug-entrapping agent, TEA-8-SOS (Triethylamine–octa-sucroseoctasulfate), which additionally defines the corresponding in-vitro drug release profile (sustained vs. rapid release). TEA-8-SOS is available as a semicrystalline, highly hygroscopic powder from Toronto Research Chemical (TRC). Nanoliposomes prepared from these semi-crystalline TEA-8-SOS have mostly gelled internal structure and based on the drug loading concentration or stability ratio (SR), produce either spherical or oblong morphology with implications on sustained in vitro irinotecan release profile. Alternatively, Na-SOS synthesized from sucrose, can be desalted using ion-exchange resins into the free acid form of SOS. However, when Sucroseoctasulfate (free acid form; that does not crystallize), when adjusted to desired pH with TEA (4.2 or 5.5), was used as a drug entrapping agent in the liquid form, the resultant nanoliposome has a precipitated internal structure of irinotecan-SOS complex as revealed in the high-resolution Cryo-TEM images Additionally, the lack of long-range interactions in their internal structure causes irinotecan to be rapidly released from these liposomes. Further, these liposomes have a spherical morphology as opposed to the oblong or prolate morphology seen in irinotecan liposomes prepared with semi-crystalline TEA-8-SOS (similar to Onivyde®). SAXS power-law analysis also confirms low fractal dimension internal structures in liposomes prepared with liquid TEA-8-SOS compared to TRC’s semi-crystalline, powder TEA-8-SOS.
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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 | 0.003 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.003 |
| 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 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".