Program of Pharmaceutical Engineering, Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom, 73000, Thailand.
Synchrotron Light Research Institute, Nakhon Ratchasima, 30000, Thailand.
AAPS PharmSciTech. 2024 Oct 14;25(7):242. doi: 10.1208/s12249-024-02960-1.
Periodontitis presents significant treatment challenges due to its complexity and potential complications. In response, an in situ forming gel (ISG) loaded with moxifloxacin HCl (Mx) and cellulose acetate butyrate (CAB) was developed for targeted periodontitis therapy. Mx-loaded 10-45% CAB-based ISGs were developed, and their physicochemical properties such as rheology, viscosity, contact angle, gel morphology and gel formation, interface interaction were investigated. Moreover, the formulation performance studies including drug release and kinetics, in vitro degradation, and antimicrobial activities were also evaluated. The Mx-loaded ISGs containing 25-45% CAB demonstrated rapid matrix formation in both macroscopic and microscopic examinations and presented plastic deformation matrix. Tracking with sodium fluorescein and Nile red fluorescence probes indicated delayed solvent movement owing to CAB matrix formation. Adequate CAB content sustained Mx release for one week, following Peppas-Sahlin model and indicating a predominantly Fickian diffusion mechanism. Higher CAB content likely contributed to a denser matrix structure, leading to a slower in vitro degradation rate. Synchrotron radiation X-ray tomographic and SEM imaging provided insights into the CAB matrix structure and porous network formation. These ISG formulations effectively inhibited Staphylococcus aureus, Escherichia coli, Candida albicans, and Porphyromonas gingivalis. The Mx-loaded 40% CAB-based ISG shows promise as a dosage form for treating periodontitis. Further clinical trials are necessary to ensure the safety of this new ISG formulation, despite existing safety data for other medicinal uses of CAB. HIGHLIGHTS: Moxifloxacin HCl-loaded 10-45% cellulose acetate butyrate (CAB)-based in situ forming gels (ISG) were developed. They were evaluated for physicochemical properties, drug release, in vitro degradation, and antimicrobial activities. ISGs with 25-45% CAB showed swift matrix formation and plastic deformation Adequate CAB content sustained Mx release with Fickian diffusion mechanism They promise for periodontitis treatment because of effective inhibition of related pathogens.
牙周炎因其复杂性和潜在并发症而带来重大治疗挑战。为此,开发了一种载有盐酸莫西沙星(Mx)和醋酸丁酸纤维素(CAB)的原位形成凝胶(ISG),用于靶向牙周炎治疗。开发了载有 10-45% CAB 的 Mx 负载的 ISG,并研究了它们的物理化学性质,如流变学、粘度、接触角、凝胶形态和凝胶形成、界面相互作用。此外,还评估了制剂性能研究,包括药物释放和动力学、体外降解和抗菌活性。在宏观和微观检查中,含有 25-45% CAB 的 Mx 负载 ISG 显示出快速的基质形成,并呈现出塑性变形基质。跟踪使用荧光素钠和尼罗红荧光探针表明,由于 CAB 基质形成,溶剂移动延迟。足够的 CAB 含量可维持 Mx 释放一周,符合 Peppas-Sahlin 模型,表明主要是 Fickian 扩散机制。更高的 CAB 含量可能导致更致密的基质结构,导致体外降解率较慢。同步辐射 X 射线断层扫描和 SEM 成像提供了对 CAB 基质结构和多孔网络形成的深入了解。这些 ISG 配方有效地抑制了金黄色葡萄球菌、大肠杆菌、白色念珠菌和牙龈卟啉单胞菌。载有 Mx 的 40% CAB 基 ISG 有望成为治疗牙周炎的剂型。尽管 CAB 其他药用用途已有安全性数据,但仍需要进行临床试验以确保这种新的 ISG 制剂的安全性。 要点: 开发了载有盐酸莫西沙星(Mx)的 10-45% 醋酸丁酸纤维素(CAB)的原位形成凝胶(ISG)。评估了它们的物理化学性质、药物释放、体外降解和抗菌活性。含有 25-45% CAB 的 ISG 显示出快速的基质形成和塑性变形。 适当的 CAB 含量以 Fickian 扩散机制维持 Mx 的释放。 它们有望用于牙周炎治疗,因为能有效抑制相关病原体。