193 IN VITRO DEVELOPMENT OF A LESS INVASIVE HORMONE DELIVERY SYSTEM TO SUPEROVULATE TIGERS
Bibliographic record
Abstract
Current administration of FSH for the purpose of superovulation of tigers is achieved through serial injections or subcutaneous osmotic pump (Blevins B et al. 2009 J. Reprod. Fertil. 21, 153 abst). Both have limitations, which are pulsatile hormone fluctuations and multiple anesthesia events for pump insertion and removal, respectively. In vivo attempts to superovulate tigers using aluminum hydroxide gel [Al(OH)3] proved unsuccessful by fecal hormone enzyme immunoassay. In addition, Al(OH)3 raises the potential for an immune response to foreign FSH. An inert, biodegradable, and FDA-approved polylactide-co-glycolide polymer-based in situ gel forming system eliminates the problems above with a single injection delivery, allowing a more natural sustained release of FSH. Polymer solutions were made using a solvent mixture of benzyl benzoate (BB), or benzyl alcohol (BA), or both. Porcine FSH (Folltropin®-V, Bioniche, Belleville, Ontario, Canada) was incorporated into the polymer solution via sonication, which gelled upon contact with interstitial fluid. Polymer composition (ratio of lactide to glycolide) and concentration and ratio of BB to BA parameters can be manipulated to achieve a desired release profile. Two formulations (F1 and F2) were created with differing percentages of composition for the purpose of recreating a controlled release rate of 100 NIH-FSH-P1 reference standard mg/day (pump output). The FSH polymer was injected into 15 mL of PBS (pH 7.4 in a 37°C shaker bath at 30 rpm), which instantly formed a gel. One milliliter of PBS was sampled every 24 h and replenished with fresh PBS. The amount of FSH was determined by measuring UV absorbance at 290 nm (Shimadzu 1600 UV-visible spectrophotometer; Shimadzu Scientific Instruments, Columbia, MD, USA). Formulation F1 showed a higher initial burst release than F2 (61.5% v. 35.8% of total incorporated hormone) as a result of the use of 100% BA as a solvent. Benzyl alcohol is more hydrophilic than BB, leaching out of the polymer-FSH solution faster and leading to a greater release of the hydrophilic FSH. Both formulations showed a biphasic release pattern in which the first phase was relatively faster than the second phase. Although F2 (80% BA-20% BB solvent) was successful in reducing the burst release by half, the day-to-day profile is below target. Our results indicate that F2 has a better release profile than F1 for inducing folliculogenesis and can be improved by manipulating formulation parameters such as increasing the polymer concentration and BA:BB ratio of the solvents. Using Fourier transform infrared spectrometry and differential scanning calorimetry, hormones before gel incorporation were compared to those released. Fourier transform infrared spectrometry and differential scanning calorimetry data suggest that the gel does not affect the conformational stability of FSH. It is therefore possible to manipulate a gel to mimic the release rate of a proven osmotic pump without compromising the functionality of the protein hormone, potentially reducing the number of surgeries or injections to superovulate tigers.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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 | 0.000 | 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 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".