Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, TX, 77030, USA.
Department of Biomedical Sciences, Texas A&M University College of Dentistry, Dallas, TX, 75246, USA.
Small. 2022 Jun;18(25):e2201561. doi: 10.1002/smll.202201561. Epub 2022 May 19.
Oral cancer has a high mortality rate, and its treatment often causes debilitating complications. More than 90% of oral cancers are oral squamous cell carcinomas (OSCCs) that may develop from clinically recognizable oral premalignant lesions (OPLs). To eradicate OPLs before they turn into cancers, a non-invasive topical formulation is developed based on a novel combination of synergistically acting oxaliplatin (OXP) and mycophenolate (MPS) embedded in a controlled-release mucoadhesive patch fabricated by computer-aided 3D printing. After multiple rounds of testing and optimization, a v6.4 ChemoPatch is designed, which shows sustained release of OXP and MPS in vitro, minimal side leakage of drugs, an average elastic modulus of 2.38 MPa, and suitable drug stability at 4 °C or below for up to 12 months. In vivo analyses show almost all patches adhere to the dorsal tongue surface for 4 hours, and display a sustained release of OXP and MPS to tongue tissue for 3-4 hours. When applied in the 4-nitroquinoline-1-oxide-induced OPL rat model, the OXP-MPS patch significantly ablates dysplastic lesions with no damage to normal epithelial cells and minimal systemic absorption and side effects. This study reports the design of a novel mucoadhesive ChemoPatch as a noninvasive therapy to treat OPLs.
口腔癌死亡率高，其治疗常导致使人虚弱的并发症。超过 90%的口腔癌是口腔鳞状细胞癌 (OSCC)，可能由临床上可识别的口腔癌前病变 (OPL) 发展而来。为了在 OPL 癌变之前将其根除，我们开发了一种基于奥沙利铂 (OXP) 和霉酚酸 (MPS) 协同作用的新型组合的非侵入性局部制剂，该制剂嵌入在计算机辅助 3D 打印制造的控释型黏附贴片中。经过多轮测试和优化，设计了一个 v6.4 化疗贴，该贴剂在体外显示出 OXP 和 MPS 的持续释放，药物的最小侧漏，平均弹性模量为 2.38 MPa，以及在 4°C 或以下长达 12 个月的稳定药物。体内分析表明，几乎所有的贴片都能在 4 小时内黏附在舌背表面，并在 3-4 小时内持续释放 OXP 和 MPS 到舌组织。当应用于 4-硝基喹啉-1-氧化物诱导的 OPL 大鼠模型时，OXP-MPS 贴片能显著消融发育不良病变，而对正常上皮细胞没有损伤，且全身吸收和副作用最小。本研究报告了一种新型黏附性化疗贴的设计，作为一种非侵入性治疗方法来治疗 OPL。
