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胆钙化醇负荷薄膜治疗鼻甲肥大体下鼻甲烧灼引起的鼻烧伤:制剂、体内研究和临床评估。

Cholecalciferol-load films for the treatment of nasal burns caused by cauterization of the hypertrophied inferior turbinate: formulation, in vivo study, and clinical assessment.

机构信息

Department of Pharmaceutics and Clinical Pharmacy, Faculty of Pharmacy, Deraya University, Minya, Egypt.

Department of Otorhinolaryngology, Faculty of Medicine, Minya University, Minya, Egypt.

出版信息

Drug Deliv Transl Res. 2023 Apr;13(4):1102-1115. doi: 10.1007/s13346-022-01275-7. Epub 2022 Dec 12.

Abstract

Nasal turbinate hypertrophy is among the most common nasal obstruction disorders, affecting the patient's quality of life significantly. Endoscopic submucosal diathermy is a prevalent cauterization procedure for treating turbinate hypertrophy. Regrettably, the nasal burn associated with diathermy typically heals slowly causing facial pain and nasal bleeding and possibly resulting in synechiae formation. In the current study, we have developed, for the first time, a polymeric film loaded with cholecalciferol for local treatment of nasal burns. The casting method was used to prepare films of different compositions of polymers such as chitosan, polyvinyl alcohol (PVA), Carbopol 971p (CP971p), and hydroxypropyl methylcellulose (HPMC) as well as a plasticizer. Several characterizations were performed for the cholecalciferol-loaded films (e.g. weight, thickness, content uniformity, surface pH, folding endurance, disintegration time, and in vitro release) to select the optimal formulation. The optimal formulation (F4) displayed compatibility between the used polymers and the drug. In vivo animal study was carried out to assess the healing efficacy of the formulated cholecalciferol-loaded film. The rabbits treated with the cholecalciferol-loaded film demonstrated significantly higher mRNA expression of the growth factor TGF-β and significantly lower mRNA expression of the proinflammatory cytokine TNF-α and IL-1β compared to the plain film treated group and the untreated control group. A randomized, single-blinded, parallel, controlled clinical trial was conducted on 20 patients scheduled to undergo endoscopic submucous diathermy. The results of the clinical study demonstrated significant reductions in facial pain and nasal bleeding scores for the nostrils treated with cholecalciferol-loaded films in comparison to the nostrils treated with plain films. Furthermore, the endoscopic examination showed good healing for 95% of the cholecalciferol-loaded film-treated nostrils. In conclusion, the optimized film can be considered an opportune approach for enhancing the healing rate of nasal burns and thus reducing the downsides of the diathermy procedure.

摘要

鼻甲肥大是最常见的鼻腔阻塞性疾病之一,严重影响患者的生活质量。内镜下鼻甲黏膜下电凝是治疗鼻甲肥大的常用方法。然而,电凝引起的鼻甲烧伤通常愈合缓慢,导致面部疼痛和鼻出血,并可能导致粘连形成。在本研究中,我们首次开发了一种载有胆钙化醇的聚合物膜,用于局部治疗鼻腔烧伤。采用浇铸法制备了不同组成的聚合物薄膜,如壳聚糖、聚乙烯醇(PVA)、卡波姆 971p(CP971p)和羟丙基甲基纤维素(HPMC)以及增塑剂。对载有胆钙化醇的薄膜进行了多项特性评估(如重量、厚度、含量均匀性、表面 pH 值、耐折性、崩解时间和体外释放),以选择最佳配方。最佳配方(F4)显示了所用聚合物与药物之间的相容性。进行了体内动物研究以评估配方载有胆钙化醇的薄膜的愈合效果。与普通薄膜处理组和未处理对照组相比,用载有胆钙化醇的薄膜处理的兔子的生长因子 TGF-β的 mRNA 表达显著升高,而促炎细胞因子 TNF-α和 IL-1β的 mRNA 表达显著降低。对 20 名计划接受内镜下鼻甲黏膜下电凝的患者进行了随机、单盲、平行、对照临床试验。临床研究结果表明,与普通薄膜处理的鼻孔相比,载有胆钙化醇的薄膜处理的鼻孔的面部疼痛和鼻出血评分显著降低。此外,内镜检查显示 95%的载有胆钙化醇的薄膜处理的鼻孔愈合良好。总之,优化后的薄膜可被视为一种提高鼻腔烧伤愈合率的方法,从而减少电凝术的弊端。

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