Sustained co-release of ciprofloxacin and dexamethasone in rabbit maxillary sinus using polyvinyl alcohol-based hydrogel microparticle

IF 4.2 3区 医学 Q2 ENGINEERING, BIOMEDICAL
Maryam Jalessi, Yasaman Tavakoli Moghaddam, Mehdi Khanmohammadi, Sajad Hassanzadeh, Zahra Azad, Mohammad Farhadi
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引用次数: 0

Abstract

Topical delivery to paranasal sinuses through sustained-release stents is one of the new horizons in treating chronic rhinosinusitis (CRS). This study aims to introduce and evaluate sustained co-release of encapsulated ciprofloxacin (CIP) and dexamethasone (DEX) in polyvinyl alcohol-based carriers within the maxillary sinus of rabbit animals. DEX and CIP were loaded in a tyramine-substituted polyvinyl alcohol microparticle (PVATyr MP). The mechanical stability, degradability, and sustained-release patterns of both drugs as well as cellular cytocompatibility were assessed in vitro. The PVATyr MPs were then injected into the maxillary sinus of rabbits and they were monitored weekly for 21 days. Nasal endoscopy, MRI imaging, and tissue microscopy were used to follow the changes and compared them with the control condition. Also, the concentrations of drugs were evaluated in the maxillary sinus and blood samples over the study period. Produced PVA-based MPs possessed a relatively narrow particle size distribution (CV 7.7%) with proper physical stability until 30 days of incubation. The uniform-sized PVATyr MPs and their surrounding hydrogel showed sustained-release profiles for DEX and CIP for up to 32 days in vitro. The injected drugs-loaded hydrogel showed complete clearance from the maxillary sinus of rabbits within 28 days. The concentrations of DEX and CIP in mucosal remained within the therapeutic window when measured on days 7, 14, and 21, which were well above the plasma concentrations without any pathological changes in endoscopy, MRI imaging, and histological examinations. DEX/CIP loaded PVATyr MPs provided an effective, controlled, and safe sustained-drug delivery in both in vitro and in vivo analyses at therapeutic concentrations with minimal systemic absorption, suggesting a promising treatment approach for CRS.

Graphical Abstract

利用聚乙烯醇基水凝胶微粒在兔上颌窦中持续释放环丙沙星和地塞米松
通过缓释支架向副鼻窦局部给药是治疗慢性鼻窦炎(CRS)的新领域之一。本研究旨在介绍和评估以聚乙烯醇为载体的环丙沙星(CIP)和地塞米松(DEX)在家兔上颌窦内的持续协同释放。DEX 和 CIP 装载在酪胺取代的聚乙烯醇微颗粒(PVATyr MP)中。在体外评估了这两种药物的机械稳定性、降解性和持续释放模式以及细胞相容性。然后将 PVATyr MPs 注入兔子的上颌窦,每周监测一次,连续 21 天。使用鼻内窥镜、核磁共振成像和组织显微镜来观察其变化,并与对照组进行比较。此外,还对研究期间上颌窦和血液样本中的药物浓度进行了评估。所生产的基于 PVA 的 MPs 具有相对较窄的粒度分布(CV 值为 7.7%),在培养 30 天前具有适当的物理稳定性。尺寸均匀的 PVATyr MPs 及其周围的水凝胶在体外显示了长达 32 天的 DEX 和 CIP 持续释放曲线。注射药物的水凝胶在 28 天内从兔子的上颌窦中完全清除。第 7 天、第 14 天和第 21 天测量的 DEX 和 CIP 在粘膜中的浓度仍在治疗窗口期内,远高于血浆浓度,内窥镜、核磁共振成像和组织学检查均未发现任何病理变化。在体外和体内分析中,负载了 DEX/CIP 的 PVATyr MPs 提供了有效、可控和安全的持续给药,达到了治疗浓度,且全身吸收率极低,是一种治疗 CRS 的有效方法。
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来源期刊
Journal of Materials Science: Materials in Medicine
Journal of Materials Science: Materials in Medicine 工程技术-材料科学:生物材料
CiteScore
8.00
自引率
0.00%
发文量
73
审稿时长
3.5 months
期刊介绍: The Journal of Materials Science: Materials in Medicine publishes refereed papers providing significant progress in the application of biomaterials and tissue engineering constructs as medical or dental implants, prostheses and devices. Coverage spans a wide range of topics from basic science to clinical applications, around the theme of materials in medicine and dentistry. The central element is the development of synthetic and natural materials used in orthopaedic, maxillofacial, cardiovascular, neurological, ophthalmic and dental applications. Special biomedical topics include biomaterial synthesis and characterisation, biocompatibility studies, nanomedicine, tissue engineering constructs and cell substrates, regenerative medicine, computer modelling and other advanced experimental methodologies.
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