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

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

Document type :

Article dans une revue scientifique: Article original

DOI :

10.1016/j.ijpharm.2024.124121

PMID :

38621617

Permalink :

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

Title :

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

Author(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]

Journal title :

International Journal of Pharmaceutics: X

Abbreviated title :

Int J Pharm

Volume number :

657

Pages :

124121

Publisher :

Elsevier

Publication date :

2024-04-18

ISSN :

1873-3476

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [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 ...
Show more >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.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

Submission date :

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

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Version	Link	Modification date
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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