{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:59:03Z","timestamp":1788839943486,"version":"build-2803163510"},"reference-count":107,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,8]],"date-time":"2022-03-08T00:00:00Z","timestamp":1646697600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian National Authority for Scientific Research and Innovation, CCCDI\u2014UEFISCDI","award":["39\/2018 COFUND-MANUNET III-HAMELDENT, within PNCDI III"],"award-info":[{"award-number":["39\/2018 COFUND-MANUNET III-HAMELDENT, within PNCDI III"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Membranes"],"abstract":"<jats:p>(1) Background: The standard treatment for periodontal disease, a chronic inflammatory state caused by the interaction between biofilms generated by organized oral bacteria and the local host defense response, consists of calculus and biofilm removal through mechanical debridement, associated with antimicrobial therapy that could be delivered either systemically or locally. The present study aimed to determine the effectiveness of a hyaluronic acid membrane matrix as a carrier for the controlled release of the active compounds of a formulation proposed as a topical treatment for periodontal disease, and the influence of pH on the complex system\u2019s stability. (2) Methods: The obtained hyaluronic acid (HA) hydrogel membrane with dispersed melatonin (MEL), metronidazole (MZ), and tetracycline (T) was completely characterized through FTIR, XRD, thermal analysis, UV-Vis and fluorescence spectroscopy, fluorescence microscopy, zeta potential and dielectric analysis. The MTT viability test was applied to check the cytotoxicity of the obtained membranes, while the microbiological assessment was performed against strains of Staphylococcus spp. and Streptococcus spp. The spectrophotometric investigations allowed to follow up the release profile from the HA matrix for MEL, MZ, and T present in the topical treatment considered. We studied the behavior of the active compounds against the pH of the generated environment, and the release profile of the bioactive formulation based on the specific comportment towards pH variation. The controlled delivery of the bioactive compounds using HA as a supportive matrix was modeled applying Korsmeyer\u2013Peppas, Higuchi, first-order kinetic models, and a newly proposed pseudo-first-order kinetic model. (3) Results: It was observed that MZ and T were released at higher active concentrations than MEL when the pH was increased from 6.75, specific for patients with periodontitis, to a pH of 7.10, characterizing the healthy patients. Additionally, it was shown that for MZ, there is a burst delivery up to 2.40 \u00d7 10\u22125 mol\/L followed by a release decrease, while for MEL and T a short release plateau was recorded up to a concentration of 1.80 \u00d7 10\u22125 mol\/L for MEL and 0.90 \u00d7 10\u22125 mol\/L for T, followed by a continuous release; (4) Conclusions: The results are encouraging for the usage of the HA membrane matrix as releasing vehicle for the active components of the proposed topical treatment at a physiological pH.<\/jats:p>","DOI":"10.3390\/membranes12030303","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:53:54Z","timestamp":1646790834000},"page":"303","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Considerations on the Controlled Delivery of Bioactive Compounds through Hyaluronic Acid Membrane"],"prefix":"10.3390","volume":"12","author":[{"given":"Eugenia","family":"Eftimie Totu","sequence":"first","affiliation":[{"name":"Department of Analytical Chemistry and Environmental Engineering, University Politehnica of Bucharest, 1\u20137 Polizu St., 011061 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"M\u0103nuc","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Dental Medicine, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiberiu","family":"Totu","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e8rale de Lausanne (EPFL), Route Cantonale, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6635-6091","authenticated-orcid":false,"given":"Corina Marilena","family":"Cristache","sequence":"additional","affiliation":[{"name":"Department of Dental Techniques, Faculty of Midwifery and Nursing (FMAM), \u201cCarol Davila\u201d University of Medicine and Pharmacy, 8 Eroii Sanitari Blvd, 050474 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxana-M\u0103d\u0103lina","family":"Buga","sequence":"additional","affiliation":[{"name":"School of Life Sciences, Ecole Polytechnique F\u00e9d\u00e8rale de Lausanne (EPFL), Route Cantonale, 1015 Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3044-7343","authenticated-orcid":false,"given":"Fatih","family":"Erci","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Faculty of Science, Necmettin Erbakan University, Yeni Meram Boulevard Kasim Halife Street, Meram, Konya 42090, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camelia","family":"Cristea","sequence":"additional","affiliation":[{"name":"Biotechnologies Center, University of Agriculture and Veterinary Medicine, 42 Blvd. M\u0103r\u0103\u015fti, 011464 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Isildak","sequence":"additional","affiliation":[{"name":"Department of Bioengineering, Yildiz Campus Barbaros Bulvari, Yildiz Technical University, Istanbul 34343, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"13834","DOI":"10.1021\/acsomega.9b01475","article-title":"Hyaluronic Acid-Based Hybrid Hydrogel Microspheres with Enhanced Structural Stability and High Injectability","volume":"4","author":"Seong","year":"2019","journal-title":"ACS Omega"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.2174\/0929867324666170705143308","article-title":"Applications of cellulose-based materials in sustained drug delivery systems","volume":"26","author":"Sun","year":"2019","journal-title":"Curr. 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