In-situ forming PLGA implants: Towards less toxic solvents.

Ramos, F.; Willart, Jean-François; Neut, Christel; Agossa, Kevimy; Siepmann, Juergen; Siepmann, Florence

Type de document :

Article dans une revue scientifique: Article original

DOI :

10.1016/j.ijpharm.2024.124121

PMID :

38621617

URL permanente :

http://hdl.handle.net/20.500.12210/114301

Titre :

In-situ forming PLGA implants: Towards less toxic solvents.

Auteur(s) :

Ramos, F. [Auteur]
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Willart, Jean-François [Auteur]

Unité Matériaux et Transformations (UMET) - UMR 8207
Unité Matériaux et Transformations - UMR 8207 [UMET]
Neut, Christel [Auteur]

Institute for Translational Research in Inflammation - U 1286 [INFINITE]
Agossa, Kevimy [Auteur]

Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]
Advanced Drug Delivery Systems (ADDS) - U1008
Siepmann, Juergen [Auteur]

Advanced Drug Delivery Systems (ADDS) - U1008
Siepmann, Florence [Auteur]

Advanced Drug Delivery Systems (ADDS) - U1008
Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 [MBLC - ADDS]

Titre de la revue :

International Journal of Pharmaceutics: X

Nom court de la revue :

Int J Pharm

Numéro :

657

Pagination :

124121

Éditeur :

Elsevier

Date de publication :

2024-04-18

ISSN :

1873-3476

Discipline(s) HAL :

Sciences du Vivant [q-bio]

Résumé en anglais : [en]

In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis treatment. The polymer is dissolved in a water-miscible ...
Lire la suite >In-situ forming poly(lactic-co-glycolic acid) (PLGA) implants offer a great potential for controlled drug delivery for a variety of applications, e.g. periodontitis treatment. The polymer is dissolved in a water-miscible solvent. The drug is dissolved or dispersed in this solution. Upon contact with aqueous body fluids, the solvent diffuses into the surrounding tissue and water penetrates into the formulation. Consequently, PLGA precipitates, trapping the drug. Often, N-methyl-2-pyrrolidine (NMP) is used as a water-miscible solvent. However, parenteral administration of NMP raises toxicity concerns. The aim of this study was to identify less toxic alternative solvent systems for in-situ forming PLGA implants. Various blends of polyethylene glycol 400 (PEG 400), triethyl citrate (TEC) and ethanol were used to prepare liquid formulations containing PLGA, ibuprofen (as an anti-inflammatory drug) and/or chlorhexidine dihydrochloride (as an antiseptic agent). Implant formation and drug release kinetics were monitored upon exposure to phosphate buffer pH 6.8 at 37 °C. Furthermore, the syringeability of the liquids, antimicrobial activity of the implants, and dynamic changes in the latter’s wet mass and pH of the release medium were studied. Importantly, 85:10:5 and 60:30:10 PEG 400:TEC:ethanol blends provided good syringeability and allowed for rapid implant formation. The latter controlled ibuprofen and chlorhexidine release over several weeks and assured efficient antimicrobial activity. Interestingly, fundamental differences were observed concerning the underlying release mechanisms of the two drugs: Ibuprofen was dissolved in the solvent mixtures and partially leached out together with the solvents during implant formation, resulting in relatively pronounced burst effects. In contrast, chlorhexidine dihydrochloride was dispersed in the liquids in the form of tiny particles, which were effectively trapped by precipitating PLGA during implant formation, leading to initial lag-phases for drug release.Lire moins >

Langue :

Anglais

Audience :

Internationale

Vulgarisation :

Non

Établissement(s) :

Université de Lille
Inserm
CHU Lille

Collections :

Date de dépôt :

2024-05-07T21:00:35Z
2024-05-29T07:32:40Z
2024-09-11T06:39:46Z

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Historique des modifications

Numéro de version	Lien	Date de modification
3	20.500.12210/114301*	2024-09-11T06:38:31Z
2	20.500.12210/114301.2	2024-05-29T07:21:54Z
1	20.500.12210/114301.1	2024-05-07T21:00:35Z

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