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

• Published in: Polymer bulletin (Berlin, Germany) Vol. 81; no. 12; pp. 11215 - 11238
• Main Authors: Mahmudi, Mahmudi, Ardhani, Retno, Pidhatika, Bidhari, Suyanta, Suyanta, Swasono, Yogi Angga, Rudianto, Reza Pahlevi, Nuryono, Nuryono
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-08-2024; Springer Nature B.V
• Subjects: Abnormalities; Antibiotics; Bacterial infections; Biocompatibility; Biomedical materials; Bones; Calcium ions; Carbonation; Characterization and Evaluation of Materials; Chemistry; Chemistry and Materials Science; Chitosan; Complex Fluids and Microfluidics; Contact angle; Crystal defects; Design parameters; Diffusion rate; Drug carriers; Drug delivery systems; Drugs; Functional groups; Gelatin; Hydrogels; Hydroxyapatite; Infections; Mechanical properties; Organic Chemistry; Original Paper; Particulate composites; Performance degradation; Pharmaceuticals; Physical Chemistry; Polymer Sciences; Polymers; Polyvinyl alcohol; Proteins; Regeneration; Scanning electron microscopy; Soft and Granular Matter; Substitute bone; Synthesis; Tensile strength; Tetraethyl orthosilicate; Tissue engineering; Water; Water absorption; Indonesia; TEOS; Chitosan; Metronidazole; Carbonated hydroxyapatite; Gelatin
• ISSN: 0170-0839; 1436-2449
• DOI: 10.1007/s00289-024-05243-8

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, Ca
2+
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 Ca
2+
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.
Graphical abstract