In-situ forming implants for the treatment of periodontal diseases: Simultaneous controlled release of an antiseptic and an anti-inflammatory drug

Autor: Celine Bassand, Kevimy Agossa, M. Lizambard, T. Menu, Florence Siepmann, Christel Neut, Olivier Huck, M. Fossart
Přispěvatelé: Médicaments et biomatériaux à libération contrôlée: mécanismes et optimisation - Advanced Drug Delivery Systems - U 1008 (MBLC - ADDS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Nanomédecine Régénérative (NanoRegMed), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de chirurgie dentaire - Strasbourg, Université de Strasbourg (UNISTRA), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The authors are very grateful to the ANR (the French National Research Agency) for their financial support (ANR-14-CE16-00025-01, ANR-14-CE16-00025-03 and ANR-14-CE16-00025-04) and to the INSERM (the French National Institute of Health and Medical Research) ('poste d’accueil 2016' for Kevimy Agossa) for their valuable support., ANR-14-CE16-0025,Imperio,Implants se formant in-situ pour le traitement des parodontites(2014), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Chemistry
Pharmaceutical
Pharmaceutical Science
Ibuprofen
02 engineering and technology
030226 pharmacology & pharmacy
chemistry.chemical_compound
0302 clinical medicine
Antiseptic
Polylactic Acid-Polyglycolic Acid Copolymer
Plasticizers
[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases
Solubility
media_common
In-situ forming implants
Drug Implants
Anti-Inflammatory Agents
Non-Steroidal
Chlorhexidine
Adhesiveness
PLGA
021001 nanoscience & nanotechnology
Controlled release
3. Good health
Solvent
Drug Combinations
0210 nano-technology
Porosity
medicine.drug
Drug
medicine.drug_class
media_common.quotation_subject
Excipients
03 medical and health sciences
[SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication
medicine
Periodontitis
[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials
Periodontal Diseases
organic chemicals
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
Drug Liberation
[SDV.SP.PG]Life Sciences [q-bio]/Pharmaceutical sciences/Galenic pharmacology
chemistry
Delayed-Action Preparations
Anti-Infective Agents
Local
Solvents
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Nuclear chemistry
Zdroj: International Journal of Pharmaceutics
International Journal of Pharmaceutics, Elsevier, 2019, 572, pp.118833. ⟨10.1016/j.ijpharm.2019.118833⟩
International Journal of Pharmaceutics, 2019, 572, pp.118833. ⟨10.1016/j.ijpharm.2019.118833⟩
ISSN: 0378-5173
DOI: 10.1016/j.ijpharm.2019.118833⟩
Popis: International audience; Different types of in-situ forming implants based on poly(lactic-co-glycolic acid) (PLGA) for the controlled dual release of an antiseptic drug (chlorhexidine) and an anti-inflammatory drug (ibuprofen) were prepared and thoroughly characterized in vitro. N-methyl-pyrrolidone (NMP) was used as water-miscible solvent, acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC) was added to enhance the implants’ stickiness/bioadhesion upon formation within the periodontal pocket. Different drug forms exhibiting substantially different solubilities were used: chlorhexidine dihydrochloride and digluconate as well as ibuprofen free acid and lysinate. The initial drug loadings were varied from 1.5 to 16.1%. In vitro drug release, dynamic changes in the pH of the surrounding bulk fluid and in the systems’ wet mass as well as polymer degradation were monitored. Importantly, the release of both drugs, chlorhexidine and ibuprofen, could effectively be controlled simultaneously during several weeks. Interestingly, the tremendous differences in the drug forms’ solubilities (e.g., factor >5000) did not translate into major differences in the resulting release kinetics. In the case of ibuprofen, this can likely (at least in part) be attributed to significant drug-polymer interactions (ibuprofen acts as a plasticizer for PLGA). In the case of chlorhexidine, the release of the much less soluble dihydrochloride was even faster compared to the more soluble digluconate (when combined with ibuprofen free acid). In the case of ibuprofen, at higher initial drug loadings also limited solubility effects within the implants seem to play a role, in contrast to chlorhexidine. In the latter case, instead, increased system porosity effects likely dominate at higher drug loadings.
Databáze: OpenAIRE
Externí odkaz: