Incorporation and controlled release of dexamethasone, triamcinolone acetonide, simvastatin and montelukast from silicone elastomer dispersions to reduce capsular contracture
Notice bibliographique
Résumé
Background: Capsular contracture (CC) is one of the most common clinical complications following breast augmentation or reconstruction surgery using implants. The foreign body reactions (FBR) due in parts to the hydrophobicity of the silicone elastomer and bacterial adherence to the implants are problematic and believed to be leading to the development of CC. A common strategy implemented to reduce FBR has been the addition of textures on the surface of the implants. While this approach has led to reduced incidence of fibrous capsule formation around implants, it has also led to an association with anaphylactic large cell lymphomas. Therefore, new strategies are needed to reduce rates of CC. Orally and intravenously administered agents such as dexamethasone (DEX), simvastatin (SIM), triamcinolone acetonide (TAA) or montelukast (MFA) have been reported as effective agents to reduce the formation of fibrous capsules. The incorporation and release of those drugs from the medical grade silicones used to manufacture breast implants have not been studied. Therefore, incorporation of these agents into either the silicone shell or gel components of the implants could offer an alternative pharmacological strategy to reduce the risks of CC and implant associated infection. Methods: Silicone elastomer films (0.3 cm thick) containing 1, 2.5 and 5% w/w DEX, SIM, TAA and MFA were prepared from medical grade addition-cure silicone elastomer dispersions (MED 6600, NuSil). Briefly, silicone parts A and B (1:1) were mixed with drug (1 min, 3000 rpm), left overnight for solvent evaporation, and then post-cured (3 hr, 90oC). Circular discs of 1 cm diameter were cut from the resulting films. Discs were incubated at 37oC, 60 rpm in a 1:4 isopropanol (IPA):water media and samples were collected every 24 hr to measure the amount of drug released using previously developed HPLC methods. Solubility of the drugs in the silicone material was measured. Briefly, thin films (1 mm thick) were cut into pieces of 2 × 2 cm and subsequently immersed in drug saturated 1:4 IPA:water media at 37oC, 60 rpm. After 6 weeks of incubation, equilibrium was reached for all the candidates and the films were analysed for the content of drug. The samples were extracted with acetone for 24 h and drug concentrations assessed by HPLC. Results: Cured 1, 2.5 and 5% w/w loaded thin films were successfully manufactured for DEX, TAA, and SIM but not for MFA; MFA appears to have reacted with the silicone during the curing and prevented the formation of cohesive films. A slow and controlled release of the loaded candidates was observed over time following a t1/2 kinetic concurring with what has been reported about other silicone types in literature. The results also showed that the release was anomalous, hence showing that the drugs were not dissolved in the material at these ratios. Therefore, the solubility of the drugs in the silicone material was measured for DEX, TAA, SIM, and MFA, and were, respectively, 0.85 +/- 0.07, 0.71 +/- 0.04, 0.46 +/- 0.02, 1.8.10-3 +/- 8.10-4 % w/w. Conclusions: Three drug candidates were successfully incorporated at different ratios into a medical grade silicone elastomer dispersion and a slow and controlled t1/2 release kinetic was observed. Solubility of all the candidates in the silicone material was determined. These preliminary results are encouraging for further development of drug- releasing breast implants.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».