Preparation and evaluation of in situ film of compound iodine oral spray for promoting oral ulcer repair
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摘要:
采用原位凝胶技术，制备了新型复方碘口腔喷雾原位膜，用于发挥缓释作用，并促进口腔溃疡创面修复。首先以喷雾状态和成膜时间为指标，对喷雾药液的处方和工艺进行优化。以成膜时间和药膜黏附性为评价指标对药液混合比例进行考察。并对最优处方制备的复方碘口腔喷雾药液的药物含量、稳定性、pH、喷雾效果，及原位膜的成膜时间、溶解性、吸湿性、保湿性、体外释放等理化性质进行考察；此外，通过细胞实验考察了成膜材料的生物相容性及复方碘口腔喷雾原位膜的促迁移效果；采用兔口腔溃疡模型，对复方碘口腔喷雾在体成膜效果及促修复效果进行评价。实验结果显示，最优处方制备的药液A和药液B的pH分别为6.21 ± 0.02和 6.42 ± 0.03，符合正常口腔黏膜pH范围；稳定性好，具有良好的喷雾状态；药液B中碘含量为（1.96 ± 0.01）mg/mL；原位膜体外成膜时间为（118.3 ± 3.6）s，口腔内成膜时间为（133.3 ± 4.6）s；24 h溶解率为（87.31 ± 1.74）%，吸湿率为（124.17 ± 7.13）%，保湿率为（26.85 ± 2.50）%；复方碘口腔喷雾原位膜中碘含量为（47.42 ± 0.39）mg/g；具有良好的柔韧性和黏附性，并具有一定的缓释效果。细胞实验中，原位膜表现出良好的促成纤维细胞迁移作用。兔口腔溃疡实验表明，复方碘口腔喷雾在体可快速成膜，并可显著促进口腔溃疡修复。本研究所开发的复方碘口腔喷雾原位膜，制备工艺稳定，并可有效促进口腔溃疡创面修复，为口腔黏膜制剂的研究和开发提供了新思路，并具有良好的转化前景。
Abstract:In this study, a new in situ film of compound iodine oral spray was prepared by in situ gel technology, which was used to exert sustained-release effect for promoting the repair of oral ulcer wounds. Firstly, the formulation and process of the spray solution were optimized according to the spray state and film-forming time. The drug-liquid mixing ratio was evaluated by film-forming time and drug film adhesion. The drug content, stability, pH, and spraying effect of compound iodine oral spray prepared by the optimal formulation were investigated; and the physicochemical properties, including film formation time, solubility, hygroscopicity, moisture retention and in vitro release of drug film were evaluated. In addition, the biocompatibility of the film-forming materials and proliferation ability of drug film were investigated by cell experiment. Through the rabbit oral ulcer model, the in vivo film-forming and repair-promoting effects of compound iodine oral spray were evaluated. The results showed that the pH of liquid A and liquid B prepared were 6.21±0.02 and 6.42±0.03, respectively, which were in line with the normal pH range of oral mucosa; liquid A and liquid B had good stability and spray state; the iodine content in solution B was (1.96±0.01) mg/mL; the in situ membrane formation time in vitro and in the oral cavity were (118.3±3.6) s and (133.3±4.6) s, respectively; the 24-hour dissolution rate was (87.31±1.74)%, the moisture absorption rate was (124.17±7.13)%, and the moisture retention rate was (26.85±2.50)%; the iodine content in the oral spray was (47.42±0.39) mg/g, with good flexibility and adhesion, as well as some slow-release effect. In cell experiment, the film-forming materials showed good biocompatibility and growth promotion ability. The results of the rabbit oral ulcer experiment showed that the compound iodine oral spray could rapidly form a film in vivo and significantly promote the repair of oral ulcer. In conclusion, the compound iodine oral spray in situ film with a stable preparation process can effectively promote the repair of oral ulcer wounds, which provides a new idea for the research of novel oral mucosa formulations, with a good prospect of transfer.
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Keywords:
- oral spray in situ membrane /
- compound iodine /
- oral ulcer /
- sustained release /
- promoting repair
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Figure 1. Film formation time of film sprays
A: Eudragit L-100; B: Calcium chloride; C: Glycerin; D: Sodium alginate; E: CMC-Na
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Figure 2. Quality evaluation of compound iodine oral spray
A: Character of liquid A; B: Character of liquid B; C: State of the solution before centrifugation; D: State of the solution after centrifugation
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Figure 3. Preparation and prescription optimization of drug film
A: Results of film formation time and adhesion properties (n=3); B: Plan view of drug film; C: Side view of drug film; D: SEM of the drug film
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Figure 4. In vitro release results of iodine-glycerol soft capsules andpharmaceutical films($\bar{x} $ ± s, n=3)
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Figure 5. Biocompatibility of free film($\bar{x} $ ± s, n=3)
A: Cell viabilities of 3T6-Swiss albino treated with free film for 24 h and 48 h; B: Fibroblast migration behaviors; C: Fibroblast migration rates after treatment with free film**P < 0.01, ***P < 0.001
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[1] Zhang XL. Discussion and analysis of treatment methods and research progress of oral ulcers[J]. J Clin Med (临床医药文献杂志), 2018, 5(55): 191-192. [2] Li JJ, Wen ZH, Lou Y, et al. Soluble epoxide hydrolase inhibitor promotes the healing of oral ulcers[J]. Clinics, 2023, 78: 100208. doi: 10.1016/j.clinsp.2023.100208
[3] He SY, Bai JF, Liu YH, et al. A polyglutamic acid/tannic acid-based nano drug delivery system: antibacterial, immunoregulation and sustained therapeutic strategies for oral ulcers[J]. Int J Pharm, 2023, 648: 123607. doi: 10.1016/j.ijpharm.2023.123607
[4] Zeng YY, Gao YJ, He LM, et al. Multifunctional polysaccharide composited microneedle for oral ulcer healing[J]. Mater Today Biol, 2023, 22: 100782. doi: 10.1016/j.mtbio.2023.100782
[5] Ge WH, Gao YJ, He LM, et al. Combination therapy using multifunctional dissolvable hyaluronic acid microneedles for oral ulcers[J]. Int J Biol Macromol, 2023, 251: 126333. doi: 10.1016/j.ijbiomac.2023.126333
[6] Zeng X, Jin X, Zhong L, et al. Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis[J]. Int J Oral Sci, 2022, 14(1): 28. doi: 10.1038/s41368-022-00178-0
[7] Dou X, Li GT, Wang S, et al. Probiotic-loaded calcium alginate/fucoidan hydrogels for promoting oral ulcer healing[J]. Int J Biol Macromol, 2023, 244: 125273. doi: 10.1016/j.ijbiomac.2023.125273
[8] Zhang ZJ, Zhang QY, Gao SN, et al. Antibacterial, anti-inflammatory and wet-adhesive poly(ionic liquid)-based oral patch for the treatment of oral ulcers with bacterial infection[J]. Acta Biomater, 2023, 166: 254-265. doi: 10.1016/j.actbio.2023.05.017
[9] Kanagalingam J, Amtha R. Povidone-iodine in dental and oral health: a narrative review[J]. J Int Oral Health, 2020, 12(5): 407. doi: 10.4103/jioh.jioh_89_20
[10] Deng QM, Wei CY, Luo JL, et al. Experimental study of Emilia sonchifolia combined with Coptidis rhizoma for the prevention and treatment of oral ulcer[J]. Open J Stomatol, 2023, 13(8): 233-242. doi: 10.4236/ojst.2023.138020
[11] Li ZY, Liang XY, Qiu ZT, et al. Ion-interferential cell cycle arrest for melanoma treatment based on magnetocaloric bimetallic-ion sustained release hydrogel[J]. Chin Chemical Lett, 2024: 109592.
[12] Shi M, Yong Q, He Y, et al. Construction and in vivo evaluation of a thermosensitive hydrogel system loading with Pseudomonas aeruginosa DNA vaccine[J]. J China Pharm Univ (中国药科大学学报), 2021, 52(2): 186-194. [13] Samiraninezhad N, Asadi K, Rezazadeh H, et al. Using chitosan, hyaluronic acid, alginate, and gelatin-based smart biological hydrogels for drug delivery in oral mucosal lesions: a review[J]. Int J Biol Macromol, 2023, 252: 126573. doi: 10.1016/j.ijbiomac.2023.126573
[14] Sha K, Li JC, Qi XL. Application and research progress of in situ gel for local treatment of periodontitis[J]. J China Pharm Univ (中国药科大学学报), 2022, 53(3): 365-375. [15] Chinese Pharmacopoeia Commission. Chinese Pharmacopoeia: Part 4(中华人民共和国药典: 四部)[S]. Beijing: China Medical Science Press, 2020: 119-120. [16] Ni R, Ma JL, Sun YL, et al. Preparation and in vitro evaluation of a new terbinafine hydrochloride bioadhesive film-forming gel[J]. J China Pharm Univ (中国药科大学学报), 2015, 46(6): 671-676. [17] Wang Q. The preparation of pulsatilla radix spray film agent (白头翁喷膜剂的研制) [D]. Qingdao: Qingdao University of Science & Technology, 2019. [18] Qi XY, Ye YF, Chen XM, et al. Construction of targeted nanoprobe based on hyaluronic acid and its anti-tumor activity in vitro[J]. J China Pharm Univ (中国药科大学学报), 2022, 53(5): 542-553. [19] Liu YN. Mucoadhesive buccal film containing ornidazole and dexamethasone for oral ulcers: in vitro and in vivo studies (奥硝唑地塞米松磷酸钠口腔贴膜的制备和评价) [D]. Wuhan: Huazhong University of Science and Technology, 2019. [20] Du C, Liu B, Hu J, et al. Determination of iodine number of activated carbon by the method of ultraviolet–visible spectroscopy[J]. Mater Lett, 2021, 285: 129137. doi: 10.1016/j.matlet.2020.129137
[21] Mao GZ, Tian SY, Shi YX, et al. Preparation and evaluation of a novel alginate-arginine-zinc ion hydrogel film for skin wound healing[J]. Carbohydr Polym, 2023, 311: 120757. doi: 10.1016/j.carbpol.2023.120757
[22] Jin FY, Liao SQ, Li W, et al. Amphiphilic sodium alginate-polylysine hydrogel with high antibacterial efficiency in a wide pH range[J]. Carbohydr Polym, 2023, 299: 120195. doi: 10.1016/j.carbpol.2022.120195
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