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Development of a local drug delivery system for promoting the regeneration of infective bone defects: composite films with controlled properties

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Abstract

Due to inadequate drug tissue penetration and low blood supply to the bone, the systemic delivery of medications during infection and inflammation of bone tissues frequently fails to heal abnormalities or lesions in bone tissues. In the quest for local delivery of antibiotics to treat the infection and bone-grafting particles to stimulate bone growth and regeneration, a series of composite films containing gelatin (G), chitosan (CH), carbonated hydroxyapatite (CHA), and various amounts of tetraethyl orthosilicate (TEOS) crosslinker were synthesized. The synthesis resulted in 4 (four) different composite films having a mass ratio of 0.3/0.3/0.5/x, where x = 0, 1.87, 3.73, and 5.60 for G/CH/CHA, G/CH/CHA/TEOS(2), G/CH/CHA/TEOS(4), and G/CH/CHA/TEOS(6), respectively. The composite films were characterized using SEM for morphology, SAA for specific surface area and pore volume, and FTIR and XRD for functional groups and crystal phase, respectively. Furthermore, tensile strength, water absorption capacity, polymer matrix degradation, Ca2+ release profile, drug loading capacity, drug unloading (release) profile, and drug release kinetics were determined to gain insights into the critical design parameters for preparing this drug carrier. A commercial film, Dentium™ (collagen-based), was included in the water absorption, drug loading capacity, drug release profile, and degradation tests. The biological performance of the film was evaluated from protein absorption and MC3T3I1 cell cytotoxicity. It was found that G/CH/CHA/TEOS(2) exhibited the lowest total pore volume, the highest tensile strength and protein absorption, similar water absorption and drug loading capacity, the lowest drug release rate, the lowest Ca2+ release rate, the lowest degradation rate, and cytocompatibility when compared to the other synthesized composite films. According to empirical mathematical modeling, the Higuchi and Korsmeyer-Peppas models best described the drug unloading (release) process for G/CH/CHA and G/CH/CHA/TEOS films through a diffusion process. When Dentium™ was included in the tests, Dentium™ exhibited the lowest water absorption, the lowest drug loading capacity, the highest drug release rate, and the lowest film degradation rate compared to all studied films.

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Acknowledgements

All authors express gratitude for the support to our research from the Directorate of Research, Technology, and Community Services, Directorate General of Higher Education, Research, and Technology, Ministry of Education, Culture, Research, and Technology Republic of Indonesia by the Fundamental of Basic Research Grant No. 122/E5/PG/02.00PL/2023; 3135/UN1/DITLIT/Dit-Lit/PT.01.03/2023, RTA Universitas Gadjah Mada for 2338/UN1/DITLIT/Dit-Lit/PT.01.00/2023, as well as LPDP and BRIN Indonesia for B-3842/II.7.5/FR.06.00/11/2023; B-3855/III.10/FR.06.00/11/2023 grants.

Funding

Directorate of Research, Technology, and Community Services, Directorate General of Higher Education, Research, and Technology, Ministry of Education, Culture, Research, and Technology Republic of Indonesia, 122/E5/PG/02.00PL/2023, Retno Ardhani, 3135/UN1/DITLIT/Dit-Lit/PT.01.03/2023, Retno Ardhani, Universitas Gadjah Mada, 2338/UN1/DITLIT/Dit-Lit/PT.01.00/2023, Nuryono Nuryono, LPDP and BRIN Indonesia, B-3842/II.7.5/FR.06.00/11/2023, Bidhari Pidhatika, B-3855/III.10/FR.06.00/11/2023, Bidhari Pidhatika.

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  1. Retno Ardhani and Bidhari Pidhatika are contributed equally to the paper.

Authors and Affiliations

  1. Faculty of Mathematics and Natural Sciences, Department of Chemistry, Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia

    Mahmudi Mahmudi, Suyanta Suyanta & Nuryono Nuryono

  2. Faculty of Dentistry, Department of Dental Biomedical Science, Universitas Gadjah Mada, Yogyakarta, 55281, Indonesia

    Retno Ardhani

  3. Research Center for Polymer Technology, National Research and Innovation Agency, Republic of Indonesia—PRTPL BRIN Indonesia, Serpong, Tangerang Selatan, 15314, Indonesia

    Bidhari Pidhatika, Yogi Angga Swasono & Reza Pahlevi Rudianto

  4. Research Collaboration Center for Biomedical Scaffolds, National Research and Innovation Agency of the Republic of Indonesia and Universitas Gadjah Mada, Sekip Utara, Yogyakarta, 55281, Indonesia

    Bidhari Pidhatika

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  1. Mahmudi Mahmudi
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Mahmudi, M., Ardhani, R., Pidhatika, B. et al. Development of a local drug delivery system for promoting the regeneration of infective bone defects: composite films with controlled properties. Polym. Bull. (2024). https://doi.org/10.1007/s00289-024-05243-8

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