Imiquimod-Loaded Chitosan-Decorated Di-Block and Tri-Block Polymeric Nanoparticles Loaded In Situ Gel for the Management of Cervical Cancer
Notice bibliographique
Résumé
Cervical intraepithelial neoplasia (CIN) is a condition that precedes cervical cancer, the second most common cancer in women worldwide [1].The primary causes of CIN and invasive cervical cancer are the human papillomavirus (HPV) virus strains 16 and 18.Current treatments for high-grade CIN involve surgical excision, associated with recurrence rates and increased risk of spontaneous abortion [2].Non-surgical alternatives, such as imiquimod (IMQ), are needed for managing CIN.IMQ induces the expression of cytokines and activates T-cells, leading to a tumor-directed immune response associated with HPV clearance [3][4][5].However, IMQ's poor water solubility and side effects may limit its effectiveness [6].Polymeric nanoparticles (NPs) are being researched for targeted drug delivery due to their advantages, such as sustained drug release and improved local availability [7].Polylactic acids (PLAs) and polycaprolactone (PCL) have gained attention for their biodegradable properties and potential for biomedical applications.]8[Mucoadhesive polymeric systems like chitosan (CS) have been used to improve the residence time of vaginal drug delivery systems [9,10].Poloxamer in situ gel-forming systems have gained attention for their ability to transform from a liquid formulation into a gel-like state at the target site [9,10].As a result, this study aims to improve the efficacy and reduce the side effects of IMQ by developing a local vaginal drug delivery system based on the loading of IMQ into NPs coated with CS and loaded in an in-situ hydrogel.Method: IMQ nanoparticles were created using polylactic-co-glycolic acid (PLGA), polycaprolactone (PCL), poly lactide-co-caprolactone (PLA-PCL), and poly L-lactide-co-caprolactone-co-glycolide (PLGA-PCL).The mucoadhesive properties of chitosan (CS) were then added to the surfaces of the IMQ NPs.The NPs were then mixed with poloxamer hydrogels.The size and morphology of the NPs, as well as their encapsulation efficiency (EE), in vitro drug release, gel characterization, ex vivo drug permeation, and in vitro safety and efficacy, were all studied.Results: IMQ NPs and CS-coated NPs (CS-IMQ NPs) were prepared in two batches.In general, both types of NPs were uniformly spherical in shape, with average particle sizes of 237.3 4.7 and 278.2 5.4 nm, respectively, and EE% of 61.48 5.19% and 37.73 2.88 for IMQ NPs and CS-IMQ NPs.In comparison to free IMQ, both systems reduced the production of inflammatory cytokines by at least 25%.Conclusion: IMQ and CS-IMQ NP in situ gels improved drug stability and release, as well as IMQ penetration through vaginal tissues.Furthermore, the new systems increased IMQ's cytotoxic effect against CC cells while decreasing inflammatory responses.As a result, these systems could be a viable alternative to commercial IMQ systems for CC management.
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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) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,002 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 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 ».