title: Mechanistic analysis of PLGA/HPMC-based in-situ forming implants for periodontitis treatment.
abstract: In-situ forming implant formulations based on poly(lactic-co-glycolic acid) (PLGA), acetyltributyl citrate (ATBC), minocycline HCl, N-methyl pyrrolidone (NMP) and optionally hydroxypropyl methylcellulose (HPMC) were prepared and thoroughly characterized in vitro. This includes electron paramagnetic resonance (EPR), nuclear magnetic resonance ((1)H NMR), mass change and drug release measurements under different conditions, optical microscopy, size exclusion chromatography (SEC) as well as antibacterial activity tests using gingival crevicular fluid samples from periodontal pockets of periodontitis patients. Based on these results, deeper insight into the physico-chemical phenomena involved in implant formation and the control of drug release could be gained. For instance, the effects of adding HPMC to the formulations, resulting in improved implant adherence and reduced swelling, could be explained. Importantly, the in-situ formed implants effectively hindered the growth of bacteria present in the patients' periodontal pockets. Interestingly, the systems were more effectively hindering the growth of pathogenic bacterial strains (e.g., Fusobacterium nucleatum) than that of strains with a lower pathogenic potential (e.g., Streptococcus salivarius). In vivo, such a preferential action against the pathogenic bacteria can be expected to give a chance to the healthy flora to re-colonize the periodontal pockets.
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France.
authors.forename: M P
authors.initials: MP
authors.lastname: Do
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 995, Inflammatory Bowel Diseases, 3 Rue du Prof. Laguesse, 59006 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Neut
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Department of Pharmaceutics and Biopharmaceutics, Halle/Saale, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Metz
authors.affiliation: INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France; University of Lille, School of Dentistry, Place de Verdun, 59000 Lille, France.
authors.forename: E
authors.initials: E
authors.lastname: Delcourt
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
authors.affiliation: Martin-Luther-University Halle-Wittenberg, Department of Pharmaceutics and Biopharmaceutics, Halle/Saale, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Mäder
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France. Electronic address: florence.siepmann@univ-lille2.fr.
authors.forename: F
authors.initials: F
authors.lastname: Siepmann
mesh_terms: D000268:Adhesiveness; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D004339:Drug Compounding; D004343:Drug Implants / Q000737:chemistry*; D065546:Drug Liberation; D005673:Fusobacterium / Q000187:drug effects / Q000254:growth & development; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D010514:Periodontal Pocket / Q000382:microbiology; D010518:Periodontitis / Q000188:drug therapy* / Q000382:microbiology; D044367:Phase Transition; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D016062:Porosity; D012997:Solvents / Q000737:chemistry; D013291:Streptococcus / Q000187:drug effects / Q000254:growth & development; D013499:Surface Properties
chemical_list: D000900:Anti-Bacterial Agents; D004343:Drug Implants; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D065347:Hypromellose Derivatives; D008911:Minocycline
keywords: Antibacterial activity; EPR; In-situ forming implant; NMR; PLGA; Periodontitis