口腔溃疡表现为复发性和自发性病变,经常引起难以忍受的灼热疼痛,严重扰乱患者的日常生活,损害他们的生活质量。为了应对这一临床挑战,口腔溶解膜(ODF)由于其快速起效,已成为治疗口腔溃疡的有前途的药物制剂,易于管理,和便携性。在这项研究中,使用以乙醇为溶剂的溶剂浇铸方法,配制含有不溶性药物地塞米松(Dex)的ODF,用于治疗兔口腔溃疡。为了优化ODF的组成,Box-Behnken设计(BBD)实验用于研究不同浓度的羟丙基纤维素(HPC)的影响,低取代羟丙基纤维素(L-HPC),和增塑剂(甘油)的关键参数,如崩解时间,抗拉强度,和薄膜的剥离效率。随后,彻底评估了Dex加载的ODF(ODF@Dex)的薄膜特性,揭示有利的属性,包括同质性,机械强度,和溶解度。值得注意的是,在ODF制剂中使用乙醇作为溶剂促进了不溶性药物在薄膜基质中的均匀分布,从而提高其溶解度和溶解速率。利用Dex的强效药理活性,进一步评估了ODF@Dex在体外和体内促进溃疡愈合和减轻炎症因子表达的功效。结果表明,ODF@Dex通过调节PI3K/Akt信号通路发挥了显著的抗溃疡作用,从而有助于溃疡的解决。总之,我们的研究强调了以乙醇为溶剂配制的基于HPC的ODF作为递送不溶性药物的有前途的平台的潜力。为口腔溃疡的临床管理提供了可行的策略。
Oral ulcers present as recurrent and spontaneous lesions, often causing intolerable burning pain that significantly disrupts patients\' daily lives and compromises their quality of life. In addressing this clinical challenge, oral dissolving films (ODFs) have emerged as promising pharmaceutical formulations for oral ulcer management due to their rapid onset of action, ease of administration, and portability. In this study, ODFs containing the insoluble drug dexamethasone (Dex) were formulated for the treatment of oral ulcers in rabbits using a solvent casting method with ethanol as the solvent. To optimize the composition of the ODFs, a Box-Behnken Design (BBD) experiment was employed to investigate the effects of varying concentrations of hydroxypropyl cellulose (HPC), low-substituted hydroxypropyl cellulose (L-HPC), and plasticizer (glycerol) on key parameters, such as disintegration time, tensile strength, and peel-off efficiency of the films. Subsequently, the film properties of the Dex-loaded ODFs (ODF@Dex) were thoroughly assessed, revealing favorable attributes, including homogeneity, mechanical strength, and solubility. Notably, the use of ethanol as the solvent in the ODF preparation facilitated the homogeneous distribution of insoluble drugs within the film matrix, thereby enhancing their solubility and dissolution rate. Leveraging the potent pharmacological activity of Dex, ODF@Dex was further evaluated for its efficacy in promoting ulcer healing and mitigating the expression of inflammatory factors both in vitro and in vivo. The findings demonstrated that the ODF@Dex exerted significant antiulcer effects by modulating the PI3K/Akt signaling pathway, thus contributing to ulcer resolution. In conclusion, our study underscores the potential of HPC-based ODFs formulated with ethanol as a solvent as a promising platform for delivering insoluble drugs, offering a viable strategy for the clinical management of oral ulcers.