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    Clindamycin phosphate and bone morphogenetic protein-7 loaded combined nanoparticle-graft and nanoparticle-film formulations for alveolar bone regeneration-An in vitro and in vivo evaluation
    (Elsevier, 2023) Ilhan, Miray; Kilicarslan, Muge; Alcigir, Mehmet Eray; Bagis, Nilsun; Ekim, Okan; Orhan, Kaan
    Commonly utilized techniques for healing alveolar bone destruction such as the use of growth factors, suffering from short half-life, application difficulties, and the ability to achieve bioactivity only in the presence of high doses of growth factor. The sustained release of growth factors through a scaffold-based delivery system offers a promising and innovative tool in dentistry. Furthermore, it is suggested to guide the host response by using antimicrobials together with growth factors to prevent recovery and achieve ideal regeneration. Herein, the aim was to prepare and an in vitro -in vivo evaluation of bone morphogenetic protein 7 (BMP-7) and clindamycin phosphate (CDP) loaded polymeric nanoparticles, and their loading into the alginate-chitosan polyelectrolyte complex film or alloplastic graft to accelerate hard tissue regeneration. PLGA nanoparticles containing CDP and BMP-7, separately or together, were prepared using the double emulsion solvent evaporation technique. Through in vitro assays, it was revealed that spherical particles were homogeneously distributed in the combination formulations, and sustained release could be achieved for >12 weeks with all formulations. Also, results from the micro-CT and histopathological analyses indicated that CDP and BMP-7 loaded nanoparticle-film formulations were more effective in treatment than the nanoparticle loaded grafts.
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    Effect of process variables on in vitro characteristics of clindamycin phosphate loaded PLGA nanoparticles in dental bone regeneration and 3D characterization studies using nano-CT
    (Elsevier, 2022) İlhan, Miray; Kılıçarslan, Müge; Orhan, Kaan
    Bone tissue surrounding the teeth may be lost due to traumatic, pathological, or physiological reasons, which can result in tooth loss. Therefore, studies in the field of dental surgery have focused on preventing bone loss around the teeth as well as bone regeneration. In the present work, clindamycin phosphate loaded polymeric nano -particles were developed as a local drug delivery system to promote alveolar bone regeneration. The effects of PVA concentration, drug/polymer ratio, inner phase content, polymer type, and pH of the external water phase on the characterization of nanoparticles were investigated by determining the encapsulation efficiency, particle size and size distribution, surface morphology, 3D structure, drug release, and release kinetics of formulations. Encapsulation efficiency was highly dependent on PVA concentration and pH of the external water phase. The mean particle size decreased with the decrease in molecular weight of PLGA. Although using clindamycin phosphate, a water soluble drug, sustained release was achieved for up to 3 months for all formulations. This study revealed that nano-CT visualization is critical in explaining the effects of process parameters on the characterization of nanoparticles. With the 3D images obtained through nano-CT, the internal and external structural properties of the nanoparticles were obtained both visually and quantitatively. The findings of nano -CT imaging that simultaneously determine the 3D structure, size, volume and porosity of nanoparticles were promising for further studies unlike SEM. The differences of internal structural properties between the nano -particles prepared using PCL and PLGA, which could not be distinguished using SEM images, were revealed through nano-CT imagery. Thus, thanks to the 2D and 3D images obtained by nano-CT, it was determined that densely capsular nanoparticles were formed using PCL, and nanoparticles in a matrix structure were formed with PLGA. In addition, the use of nano-CT scanning was particularly effective in interpreting the dissolution rate. Imaging the internal structures of the nanoparticles gave interpretable results in the formulation choices made in this study.