Development and characterization of stimuli-responsive drug delivery systems to prevent HIV infection and the treatment of chronic wounds
Notice bibliographique
Résumé
Patient compliance is very important and highly depends on the drug dosage form which correlates with the success of therapy. Drug delivery systems can be adapted to different pharmaceutical ingredients and to different delivery routes depending on the application. This thesis focuses on the development and characterization of different types of drug delivery systems with a focus on stimuli-responsive biomaterials. Stimuli-responsive biomaterials are a promising approach for achieving on-demand drug release. They are intended to deliver their active compound at the appropriate time and site of action in response to specific triggers. The aim of this thesis was the development and characterization of a pH-responsive intravaginal ring (IVR) and a thermo-responsive wound dressing. The IVR is intended for the prevention of HIV infection while the wound dressing is to treat chronic wounds that develop as a co-morbidity associated with immune-compromised patients. \nThe behavior of polyvinyl alcohol (PVA) films containing nanoparticles (NPs) for vaginal drug delivery was evaluated first. In this study, we demonstrated that the amount of NPs had little effect on film dissolution and on the storage and loss modulus. However, the percentage of PVA used and the amount of plasticizer (polyethylene glycol) and carrageenan (a film-forming agent) greatly affected the physico-mechanical properties of the film and play an important role in film dissolution time and nanoparticle (NP) release. \n Secondly, we fabricated an IVR with polyurethane HP-60D-35 containing hydroxychloroquine (HCQ) as a prevention strategy against HIV. The safety of the IVR and HCQ were assessed on the vaginal epithelial cells VK2/E6E7, the ectocervical cells ECT1 and more importantly, on vaginal normal microflora lactobacillus crispatus and jensenii. No significant toxicity was observed. \n We then designed a segmented IVR with half of the ring delivering HCQ while the second-half was coated with a pH-responsive polymer to deliver anti-CCR5 siRNA NPs. HCQ was released continuously for over 25 days with a mean daily release of 31.17±3.06 µg/mL. Anti-CCR5 siRNA NPs were released from the pH-responsive coated segment only when the pH was 7.3 (e.g. in the presence of simulated seminal fluid) with a total release of 5.12 ±0.9 mg compared to vaginal fluid simulant alone (0.42 ±0.19 mg). Anti-CCR5 siRNA NPs knocked down CCR5 gene expression by 83±5.1% in vitro in the CD4+ T-cell line Sup-T1. \n In the second part of the thesis, we made a thermo-responsive wound dressing using gelatin crosslinked with chitosan. LL37 and vancomycin were encapsulated into solid lipid nanoparticles (SLN) and mixed into the gelatin-chitosan hydrogel. The hydrogel itself liquefied rapidly (30min) at 33ºC (human skin temperature) than at room temperature (remained semisolid). We evaluated LL37/vancomycin-SLN using a microtiter plate-based biofilm assay formed using S. aureus. 6mg/mL of LL37/vancomycin was capable of significantly reducing S. aureus biomass. \nOverall, the development of stimuli-responsive drug delivery systems is appealing as it can release drugs only when needed, which will reduce toxicity and unwanted side-effects. Furthermore, it can potentially improve patient compliance resulting in improved therapeutic efficacy.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 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) | 0,000 | 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 tête enseignante, 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 ».