In-situ forming PLGA implants: Towards less toxic solvents

被引:3
作者
Ramos, F. [1 ,2 ]
Willart, J-F. [2 ]
Neut, C. [3 ]
Agossa, K. [1 ]
Siepmann, J. [1 ]
Siepmann, F. [1 ]
机构
[1] Univ Lille, Inserm, CHU Lille, U1008, F-59000 Lille, France
[2] Univ Lille, CNRS, INRAE, Cent Lille,UMR 8207 UMET, F-59000 Lille, France
[3] Univ Lille, Inserm, CHU Lille, U1286, F-59000 Lille, France
关键词
In-situ forming implant; PLGA; Periodontitis; Solvent; Chlorhexidine; Ibuprofen; DRUG-DELIVERY; PERIODONTITIS TREATMENT; CONTROLLED-RELEASE; SUSTAINED-RELEASE; MICROSPHERES; DEPOT; VIVO; MECHANISMS; SYSTEM; VITRO;
D O I
10.1016/j.ijpharm.2024.124121
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 antiinflammatory 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 degrees 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.
引用
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页数:10
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