Antifungal ocular drug delivery via contact lenses using a novel in vitro eye model
Notice bibliographique
Résumé
Purpose: \nThe purpose of this thesis was to evaluate the potential of contact lenses (CLs) as an antifungal drug delivery device, and to develop an in vitro eye model to test thereof. \n \nMethods: \nThe first three chapters focused on developing a CL to function as a drug delivery device for natamycin, the only commercially available antifungal: \n•\tIn the first experiment (Chapter 3), the in vitro uptake and release characteristics of natamycin from several commercially available CLs were evaluated \n•\tIn the second experiment (Chapter 4), to improve the release characteristics of natamycin from contact lenses, an attempt was made to incorporate novel drug-encapsulated nanoparticles (Dex-b-PLA) within the CLs \n•\tIn the third experiment (Chapter 5), an alternative strategy employing the incorporation of cyclodextrin (CDs) within the CL polymer matrix was evaluated as a potential modification to prolong the release of natamycin \nThe second half of the thesis was aimed at developing a sophisticated in vitro ocular model capable of adequately measuring drug release from CLs: \n•\tIn Chapter 6, the design of a novel in vitro eye model to simulate the physiological ocular environment was outlined \n•\tIn Chapter 7, this model was used to evaluate the release of the antifungal fluconazole from commercially daily disposable CLs \n•\tIn chapter 8, as an extension of the developed in vitro eye model, an agar eye model was developed to test the effects of natamycin and fluconazole-releasing CLs on Candida albicans \n \nResults \nCommercial CLs, after drug incubation with natamycin, will release the drug rapidly within the first half hour, followed by a plateau phase. However, when CL materials were loaded instead with natamycin encapsulated within novel Dex-b-PLA nanoparticles, the release duration was extended to 12 hours. Modifying the CL polymer with methacrylated CDs did not significantly improve drug release. On the contrary, high loading of CDs decreased overall drug delivery efficiency, likely resulting from unfavourable arrangements of the CDs within the polymer network. \nThe developed ocular platform, termed Ocuflow, simulates physiological tear flow, tear volume, air exposure and mechanical wear. When this system was used to analyze the release of fluconazole from commercial CLs, the drug release was sustained for up to 24 hours. This observation significantly contrasts drug release observed in a vial, which typically follows a burst-plateau profile. When CLs releasing natamycin and fluconazole were tested on agar eye models that were inoculated with Candida albicans, the growth of the yeast was limited by natamycin-containing CLs. The cell morphology of the yeast also differed noticeably based on drug-lens combinations. \n \nConclusions \nThis thesis details potential strategies to develop novel CLs for antifungal ocular drug delivery. The Ocuflow system developed from this thesis is highly versatile; not only can it be used effectively to measure drug release from CLs, but it can also be applied to other in vitro analyses with CLs.
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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) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,001 |
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 ».