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用于口腔医学治疗应用的静电纺丝粘膜粘附膜的制备。

Fabrication of Electrospun Mucoadhesive Membranes for Therapeutic Applications in Oral Medicine.

机构信息

School of Clinical Dentistry, University of Sheffield , 19 Claremont Crescent, S10 2TA Sheffield, U.K.

Dermtreat ApS , Abildgaardsvej 174, 2830 Virum, Denmark.

出版信息

ACS Appl Mater Interfaces. 2017 Apr 5;9(13):11557-11567. doi: 10.1021/acsami.7b02337. Epub 2017 Mar 24.

Abstract

Oral mucosal lesions are related to several etiologies, including trauma, infection, and immunologic and neoplastic diseases. Their prevalence varies greatly depending on ethnicity, gender, and exposure to risk factors. Currently, most oral mucosal lesions are treated with creams, mouthwashes, or gels containing suitable drugs. However, topical medications may be relatively ineffective as they are removed rapidly from oral surfaces, limiting drug contact times. Systemic medications might be more effective but are associated with unacceptable off-target side effects. The aim of this study was to produce novel polymeric mucoadhesive membranes for therapeutic applications on the oral mucosa using electrospinning. Poly(vinylpyrrolidone) (PVP) and Eudragit RS100 (RS100) were used for the fabrication of membranes, whereas dextran (Dex) or poly(ethylene oxide) (PEO) particles were incorporated to enhance their mucoadhesive properties. An electrospun poly(caprolactone) (PCL) backing layer (BL) was added to create a dual-layer system. Solution properties were studied using rheometry, and membranes were characterized using differential thermal analysis and scanning electron microscopy. Solubility, surface hydrophobicity, and adhesion properties were also investigated. The solution viscosity varied depending on the composition and concentration, affecting fiber production. The addition of RS100 to PVP resulted in reduced membrane porosity and solubility, and increased surface hydrophobicity and in vitro adhesion times. Dex and PEO particles were located on the surface of the fibers. A PCL BL was successfully produced, with enhanced attachment between layers achieved through thermal treatment. PVP homopolymer membranes did not adhere to plastic or porcine mucosa, whereas PVP/RS100 membranes with and without PEO or Dex were tightly adherent. In conclusion, PVP and RS100 may be combined to tailor membrane properties. Furthermore, electrospinning facilitated the production of membranes consisting of mucoadhesive-fabricated fibers displaying increased surface area and long-lasting adhesive properties. These novel compositions exhibit great potential for the fabrication of mucoadhesive patches for therapeutic applications in oral medicine.

摘要

口腔黏膜病变与多种病因有关,包括创伤、感染、免疫和肿瘤性疾病。其患病率因种族、性别和暴露于危险因素而异。目前,大多数口腔黏膜病变采用含有合适药物的乳膏、漱口水或凝胶进行治疗。然而,由于这些药物会迅速从口腔表面清除,限制了药物接触时间,因此局部用药可能效果相对较差。全身用药可能更有效,但会引起不可接受的非靶标副作用。本研究旨在使用静电纺丝技术制备新型聚合物黏膜粘附性膜,用于口腔黏膜的治疗应用。聚(乙烯基吡咯烷酮)(PVP)和 Eudragit RS100(RS100)用于制备膜,而葡聚糖(Dex)或聚氧化乙烯(PEO)颗粒被掺入以增强其黏膜粘附性能。添加电纺聚己内酯(PCL)背衬层(BL)以形成双层系统。使用流变学研究溶液性质,使用差示热分析和扫描电子显微镜对膜进行表征。还研究了溶解度、表面疏水性和粘附性能。溶液粘度取决于组成和浓度,影响纤维的产生。RS100 的加入降低了膜的孔隙率和溶解度,增加了表面疏水性和体外粘附时间。Dex 和 PEO 颗粒位于纤维表面。成功制备了 PCL BL,通过热处理实现了层间的牢固附着。PVP 均聚物膜不粘附于塑料或猪黏膜,而含有或不含有 PEO 或 Dex 的 PVP/RS100 膜则紧密粘附。总之,PVP 和 RS100 可以结合以调整膜的性能。此外,静电纺丝有助于制备由具有高表面积和持久粘附性的黏膜粘附纤维组成的膜。这些新型组合物在用于口腔医学治疗应用的黏膜粘附贴片的制备方面具有很大的潜力。

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