Poloxamer407/gellan gum-based in situ hydrogels for ocular co-delivery of antibiotics and corticosteroids

IF 4.4 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Mojtaba Fathollahzadeh Marandi , Azam Safary , Elaheh Dalir Abdolahinia , Marziyeh Fathi , Jaleh Barar , Yadollah Omidi
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Abstract

To tackle the ocular inflammation and infection, we developed a Poloxamer 407 (PM)-gellan gum (GG)-based (PM-GG) in situ hydrogels containing dexamethasone (DEX)-loaded chitosan (CS) nanoparticles (DEX-CSNPs), neomycin sulfate (NMS), and polymixin b sulfate (PMB). Such a hybrid hydrogel was developed for the localized co-delivery of antibiotics and corticosteroids. The physicochemical properties of DEX-CSNPs (i.e., size: 286 nm, zeta potential: 20.3, entrapment efficiency: 29.4 %, and loading capacity: 6.5 %) displayed their suitability for ocular applications. To have the desired mucoadhesive hydrogel system, various combinations of GG and PM were examined. The mixture of 0.1 % GG and 16.5 % PM showed a significant increase in viscosity compared to 16.5 % PM alone. The porous structure of hydrogels was also observed from the SEM analysis, in which the pore size of PM gel decreased with the addition of GG. The PM-GG hydrogels reached less swelling percentage compared to PM hydrogels due to the higher viscosity of PM-GG hydrogels. Additionally, drug release studies and the antimicrobial test showed prolonged and effective release of drugs from PM-GG in situ hydrogels. Cell viability assay showed that the optimized formulation is well tolerated by cells with no obvious toxic effect on human umbilical vein endothelial cells (HUVECs). Collectively, the designed formulation is proposed as a novel drug delivery system for ocular codelivery of antibiotics and corticosteroids.
Poloxamer407/结冷胶基原位水凝胶用于抗生素和皮质类固醇的眼部共给药。
为了解决眼睛炎症和感染,我们开发了一种基于poloxam407 (PM)-结冷胶(GG)的原位水凝胶,其中含有(PM-GG) -负载地塞米松(DEX)的壳聚糖(CS)纳米颗粒(DEX- csnp)、硫酸新霉素(NMS)和硫酸多粘菌素b (PMB)。这种混合水凝胶是为抗生素和皮质类固醇的局部共递送而开发的。dex - csnp的理化性质(尺寸:286 nm, zeta电位:20.3,包封效率:29.4 %,负载能力:6.5 %)表明其适合于眼部应用。为了得到理想的黏附水凝胶体系,研究了GG和PM的不同组合。与单独使用16.5 % PM相比,0.1 % GG和16.5 % PM的混合物粘度显著增加。通过SEM分析还观察到水凝胶的多孔结构,随着GG的加入,PM凝胶的孔径减小,PM-GG水凝胶的溶胀率比PM水凝胶小,这是由于PM-GG水凝胶的粘度更高。此外,药物释放研究和抗菌试验表明PM-GG原位水凝胶的药物释放时间较长且有效。细胞活力实验表明,优化后的配方对细胞耐受性良好,对人脐静脉内皮细胞无明显毒性作用。总的来说,设计的配方被提出作为抗生素和皮质类固醇眼部共递送的新型药物递送系统。
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来源期刊
CiteScore
8.80
自引率
4.10%
发文量
211
审稿时长
36 days
期刊介绍: The European Journal of Pharmaceutics and Biopharmaceutics provides a medium for the publication of novel, innovative and hypothesis-driven research from the areas of Pharmaceutics and Biopharmaceutics. Topics covered include for example: Design and development of drug delivery systems for pharmaceuticals and biopharmaceuticals (small molecules, proteins, nucleic acids) Aspects of manufacturing process design Biomedical aspects of drug product design Strategies and formulations for controlled drug transport across biological barriers Physicochemical aspects of drug product development Novel excipients for drug product design Drug delivery and controlled release systems for systemic and local applications Nanomaterials for therapeutic and diagnostic purposes Advanced therapy medicinal products Medical devices supporting a distinct pharmacological effect.
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