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.
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Batool, Fareeha
;
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Agossa, Kevimy
;
Lizambard, Martin
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille, INSERM, CHU Lille, Controlled Drug Delivery Syst & Biomat U1008, F-59000 Lille, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Lizambard, Martin
;
Petit, Catherine
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Petit, Catherine
;
Bugueno, Isaac Maximiliano
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Bugueno, Isaac Maximiliano
;
Delcourt-Debruyne, Elisabeth
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h-index: 0
机构:
Univ Lille, INSERM, CHU Lille, Controlled Drug Delivery Syst & Biomat U1008, F-59000 Lille, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Delcourt-Debruyne, Elisabeth
;
Benkirane-Jessel, Nadia
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h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Benkirane-Jessel, Nadia
;
Tenenbaum, Henri
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Tenenbaum, Henri
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Siepmann, Juergen
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Siepmann, Florence
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille, INSERM, CHU Lille, Controlled Drug Delivery Syst & Biomat U1008, F-59000 Lille, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
机构:
US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Res & Stand, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Wang, Yan
;
Qin, Bin
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Res & Stand, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Qin, Bin
;
Xu, Xiaoming
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Off Testing & Res, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Xu, Xiaoming
;
Li, Qi
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Res & Stand, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Li, Qi
;
Smith, William C.
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Off Testing & Res, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Smith, William C.
;
Lynd, Nathaniel A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas Austin, McKetta Dept Chem Engn, Austin, TX 78712 USA
Univ Texas Austin, Texas Mat Inst, Austin, TX 78712 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Lynd, Nathaniel A.
;
Zhang, Feng
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
机构:
Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Impax Labs Inc, Hayward, CA 94544 USAUniv Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Ding, Amy G.
;
Schwendeman, Steven P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Batool, Fareeha
;
论文数: 引用数:
h-index:
机构:
Agossa, Kevimy
;
Lizambard, Martin
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille, INSERM, CHU Lille, Controlled Drug Delivery Syst & Biomat U1008, F-59000 Lille, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Lizambard, Martin
;
Petit, Catherine
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Petit, Catherine
;
Bugueno, Isaac Maximiliano
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Bugueno, Isaac Maximiliano
;
Delcourt-Debruyne, Elisabeth
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille, INSERM, CHU Lille, Controlled Drug Delivery Syst & Biomat U1008, F-59000 Lille, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Delcourt-Debruyne, Elisabeth
;
Benkirane-Jessel, Nadia
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Benkirane-Jessel, Nadia
;
Tenenbaum, Henri
论文数: 0引用数: 0
h-index: 0
机构:
INSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Univ Strasbourg, Fac Chirurg Dent, 8 Rue St Elisabeth, F-67000 Strasbourg, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
Tenenbaum, Henri
;
论文数: 引用数:
h-index:
机构:
Siepmann, Juergen
;
Siepmann, Florence
论文数: 0引用数: 0
h-index: 0
机构:
Univ Lille, INSERM, CHU Lille, Controlled Drug Delivery Syst & Biomat U1008, F-59000 Lille, FranceINSERM French Natl Inst Hlth & Med Res, FMTS, Regenerat Nanomed, UMR 1260, Strasbourg, France
机构:
US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Res & Stand, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Wang, Yan
;
Qin, Bin
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Res & Stand, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Qin, Bin
;
Xu, Xiaoming
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Off Testing & Res, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Xu, Xiaoming
;
Li, Qi
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Res & Stand, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Li, Qi
;
Smith, William C.
论文数: 0引用数: 0
h-index: 0
机构:
US FDA, Off Testing & Res, Off Pharmaceut Qual, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Smith, William C.
;
Lynd, Nathaniel A.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas Austin, McKetta Dept Chem Engn, Austin, TX 78712 USA
Univ Texas Austin, Texas Mat Inst, Austin, TX 78712 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
Lynd, Nathaniel A.
;
Zhang, Feng
论文数: 0引用数: 0
h-index: 0
机构:
Univ Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USAUniv Texas Austin, Coll Pharm, Dept Mol Pharmaceut & Drug Delivery, Austin, TX 78712 USA
机构:
Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Impax Labs Inc, Hayward, CA 94544 USAUniv Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA
Ding, Amy G.
;
Schwendeman, Steven P.
论文数: 0引用数: 0
h-index: 0
机构:
Univ Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USAUniv Michigan, Dept Pharmaceut Sci, Ann Arbor, MI 48109 USA