The Effect of Cross-linking Efficiency of Drug-Loaded Novel Freeze Gelated Chitosan Templates for Periodontal Tissue Reg

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Research Article The Effect of Cross-linking Efficiency of Drug-Loaded Novel Freeze Gelated Chitosan Templates for Periodontal Tissue Regeneration Syed Saad B. Qasim,1,2,5

Liebert Parreiras Nogueria,1 Amr S. Fawzy,3 and Umer Daood4

Received 12 January 2020; accepted 7 May 2020 Abstract. Innovative strategies for periodontal regeneration have been the focus of research clusters across the globe for decades. In order to overcome the drawbacks of currently available options, investigators have suggested a novel concept of functionally graded membrane (FGM) templates with different structural and morphological gradients. Chitosan (CH) has been used in the past for similar purpose. However, the composite formulation of composite and tetracycline when cross-linked with glutaraldehyde have received little attention. Therefore, the purpose of the study was to investigate the drug loading and release characteristics of novel freeze gelated chitosan templates at different percentages of glutaraldehyde. These were cross-linked with 0.1 and 1% glutaraldehyde and loaded with doxycycline hyclate. The electron micrographs depicted porous morphology of neat templates. After cross-linking, these templates showed compressed ultrastructures. Computerized tomography analysis showed that the templates had 88 to 92% porosity with average pore diameter decreased from 78 to 44.9 μm with increasing concentration. Fourier transform infrared spectroscopy showed alterations in the glycosidic segment of chitosan fingerprint region which after drug loading showed a dominant doxycycline spectral composite profile. Interestingly, swelling profile was not affected by cross-linking either at 0.1 and 1% glutaraldehyde and template showed a swelling ratio of 80%, which gained equilibrium after 15 min. The drug release pattern also showed a 40 μg/mL of release after 24 h. These doxycycline-loaded templates show their tendency to be used in a functionally graded membrane facing the defect site. KEY WORDS: chitosan; doxycycline hyclate; glutaraldehyde; functionally graded; periodontitis.

INTRODUCTION Innovative strategies for periodontal regeneration have been the focus of research clusters across the globe for decades (1–3). A number of different treatment modalities are available to clinicians for regenerating lost tooth supporting structures. Amongst the available options, a guided tissue regenerative (GTR) membrane is commonly used. These membranes are either used alone or in combination with other bone substitutes (4). Therefore, they are able 1

Department of Biomaterials, Institute of Clinical Dentistry, University of Oslo, Oslo, Norway. 2 Department of Bioclinical Sciences, Faculty of Dentistry, Kuwait University, PO-Box 24923, 11310, Safat, Kuwait. 3 UWA Dental School, University of Western Australia, 17 Monash Avenue, Nedlands, WA 6009, Australia. 4 Clinical Dentistry Division, Restorative Division, School of Dentistry, International Medical University Kuala Lumpur, 126, Jalan Jalil Perkasa 19, Bukit Jalil 57000, Wilayah Persekutuan, Kuala Lum