Biocompatibility Evaluation of a Dexamethasone Mucoadhesive Nanosystem: Preclinical and Preliminary Clinical Evaluations.

Graciela Lizeth Pérez-González, Luis Jesús Villarreal-Gómez, Lucia Margarita Valenzuela-Salas, Edgar Ramiro Méndez-Sánchez, Jose Manuel Cornejo-Bravo
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Abstract

Introduction: There is a strong need for drug delivery systems that are both highly compatible with biological tissues and effective when used in the oral mucosa. While gels, creams, or ointments are currently employed for this purpose, their oral bioavailability is constrained by the limited contact time with mucosal tissue.

Method: In response to this challenge, we developed and evaluated the efficacy of a multilayer mucoadhesive system incorporated with Dexamethasone Sodium Phosphate (DEX-P) for oral mucosal delivery. An electrospun multilayer system was created and subjected to biocompatibility and efficiency testing through both in vitro and ex vivo approaches, finally culminating in an acceptability trial in healthy human volunteers. The multilayer system was created using Poly-Vinyl Pyrrolidone (PVP) and Poly ε-Caprolactone (PCL) as a polymeric base and Polycarbophil (NOVEON® AA-1, PCF) serving as an adhesion enhancer to facilitate the unidirectional release of Dexamethasone Sodium Phosphate (DEX-P).

Result: The nanofibers matrices underwent morphological characterization by Scanning Electron Microscopy (SEM), and DEX-P release was evaluated using ex vivo porcine mucosa, yielding promising results. In vitro cytotoxicity was evaluated through the MTT assay, employing HFF-1 cells. The cell viability ranged from 78 to 96%, suggesting the safety of the polymers used. The tested dose range of DEX on cell lines did not decrease below 75%, indicating its safety in terms of in vivo cytotoxicity. Biocompatibility was evaluated on animal models, with no considerable tissue damage observed.

Conclusion: Human in vivo studies demonstrated prolonged adhesion and a favorable perception of the system.

地塞米松黏附纳米系统的生物相容性评价:临床前和初步临床评价。
导读:目前迫切需要既能与生物组织高度相容,又能在口腔黏膜中有效使用的给药系统。虽然凝胶、乳霜或软膏目前用于此目的,但它们的口服生物利用度受到与粘膜组织接触时间有限的限制。方法:为了应对这一挑战,我们开发并评估了结合地塞米松磷酸钠(DEX-P)的多层黏附系统用于口腔粘膜给药的疗效。制备了一种静电纺多层体系,并通过体外和离体方法进行了生物相容性和效率测试,最终在健康人体志愿者中进行了可接受的试验。该多层体系以聚乙烯基吡咯烷酮(PVP)和聚ε-己内酯(PCL)为聚合物基,聚碳酚(NOVEON®AA-1, PCF)为粘附增强剂,促进地塞米松磷酸钠(DEX-P)的单向释放。结果:利用扫描电镜(SEM)对纳米纤维基质进行了形态表征,并利用离体猪粘膜对DEX-P的释放进行了评估,结果令人鼓舞。采用HFF-1细胞,通过MTT法评估体外细胞毒性。细胞存活率从78%到96%不等,表明所使用的聚合物是安全的。DEX对细胞系的剂量范围不低于75%,表明其在体内细胞毒性方面是安全的。在动物模型上进行了生物相容性评估,未观察到明显的组织损伤。结论:人体体内研究表明,该系统具有持久的粘附性和良好的感知。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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