Khaing Ei Mon, Lertsuphotvanit Nutdanai, Thammasut Warakon, Rojviriya Catleya, Chansatidkosol Siraprapa, Phattarateera Supanut, Pichayakorn Wiwat, Phaechamud Thawatchai
Program of Pharmaceutical Engineering, Department of Industrial Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Faculty of Pharmaceutical Sciences, Burapha University, Chonburi 20131, Thailand.
Polymers (Basel). 2024 Dec 13;16(24):3477. doi: 10.3390/polym16243477.
Cellulose acetate butyrate is a biodegradable cellulose ester bioplastic produced from plentiful natural plant-based resources. Solvent-exchange-induced in situ gels are particularly promising for periodontitis therapy, as this dosage form allows for the direct delivery of high concentrations of antimicrobial agents to the localized periodontal pocket. This study developed an in situ gel for periodontitis treatment, incorporating a combination of metronidazole and doxycycline hyclate, with cellulose acetate butyrate serving as the matrix-forming agent. Consequently, assessments were conducted on the physicochemical properties, gel formation, drug permeation, drug release, morphological topography, and antimicrobial activities of the formulation. The formulation demonstrated an increased slope characteristic of Newtonian flow at higher bioplastic concentrations. The adequate polymer concentration facilitated swift phase inversion, resulting in robust, solid-like matrices. The mechanical characteristics of the transformed in situ gel typically exhibit an upward trend as the polymer concentration increased. The utilization of sodium fluorescein and Nile red as fluorescent probes effectively tracked the interfacial solvent-aqueous movement during the phase inversion of in situ gels, confirming that the cellulose acetate butyrate matrix delayed the solvent exchange process. The initial burst release of metronidazole and doxycycline hyclate was minimized, achieving a sustained release profile over 7 days in in situ gels containing 25% and 40% cellulose acetate butyrate, primarily governed by a diffusion-controlled release mechanism. Metronidazole showed higher permeation through the porcine buccal membrane, while doxycycline hyclate exhibited greater tissue accumulation, both influenced by polymer concentration. The more highly concentrated polymeric in situ gel formed a uniformly porous structure. Metronidazole and doxycycline hyclate-loaded in situ gels showed synergistic antibacterial effects against and . Over time, the more highly concentrated polymeric in situ gel showed superior retention of antibacterial efficacy due to its denser cellulose acetate butyrate matrix, which modulated drug release and enhanced synergistic effects, making it a promising injectable treatment for periodontitis, particularly against .
醋酸丁酸纤维素是一种可生物降解的纤维素酯生物塑料，由丰富的天然植物资源制成。溶剂交换诱导的原位凝胶在牙周炎治疗中特别有前景，因为这种剂型允许将高浓度的抗菌剂直接递送至局部牙周袋。本研究开发了一种用于牙周炎治疗的原位凝胶，其包含甲硝唑和盐酸多西环素的组合，以醋酸丁酸纤维素作为基质形成剂。因此，对该制剂的物理化学性质、凝胶形成、药物渗透、药物释放、形态拓扑结构和抗菌活性进行了评估。该制剂在较高生物塑料浓度下表现出牛顿流体增加的斜率特征。适当的聚合物浓度促进了快速相转变，从而形成坚固的、类似固体的基质。随着聚合物浓度增加，转化后的原位凝胶的机械特性通常呈现上升趋势。利用荧光素钠和尼罗红作为荧光探针有效地追踪了原位凝胶相转变过程中的界面溶剂 - 水相运动，证实醋酸丁酸纤维素基质延迟了溶剂交换过程。甲硝唑和盐酸多西环素的初始突释被最小化，在含有25%和40%醋酸丁酸纤维素的原位凝胶中实现了7天的持续释放曲线，主要受扩散控制释放机制支配。甲硝唑在猪颊膜中表现出更高的渗透性，而盐酸多西环素表现出更大的组织蓄积，两者均受聚合物浓度影响。更高浓度的聚合物原位凝胶形成了均匀的多孔结构。负载甲硝唑和盐酸多西环素的原位凝胶对[具体菌种1]和[具体菌种2]显示出协同抗菌作用。随着时间推移，更高浓度的聚合物原位凝胶由于其更致密的醋酸丁酸纤维素基质而表现出优异的抗菌功效保留，该基质调节药物释放并增强协同作用，使其成为一种有前景的牙周炎注射治疗方法，尤其针对[具体菌种1]。
