Biogenic Amino Acid Cross-Linked Hyaluronic Acid Nanoparticles Containing Dexamethasone for the Treatment of Dry Eye Syndrome

IF 3.4 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Ajit Mishra, Jitu Halder, Ivy Saha, Vineet Kumar Rai, Ritu Mahanty, Deepak Pradhan, Priyanka Dash, Chandan Das, Tushar Kanti Rajwar, Bibhanwita Satpathy, Salim Manoharadas, Muralidhar Tata, Amit Goyal, Biswakanth Kar, Goutam Ghosh, Goutam Rath
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Abstract

Ocular barriers, poor retention time, and frequent ocular discharge suppress the activity of Dexamethasone. Arginine (Arg) and hyaluronic acid (HA) are crucial for maintaining ocular health because of their unique biological benefits. In this study, we investigated the cationic properties of arginine to develop dexamethasone-loaded HA nanoparticles (ADHA NPs) and evaluated their therapeutic potential in alleviating dry eye syndrome using various reported in-vitro and in-vivo techniques. The ionic cross-linking method was used to prepare ADHA NPs. The ADHA NPs exhibited nearly 94.99 ± 4.16% drug release at the end of 6 h and followed the Korsemeyar-Peppas kinetic model (R2 = 0.9811). Moreover, the developed formulation exhibited a higher water retention capacity, i.e., 86.89 ± 1.41%, and revealed enhanced mucoadhesion characteristics. ADHA NPs also exhibited significant anti-inflammatory effects (p < 0.001) compared to dexamethasone in LPS-induced RAW 264.7 cell lines against proinflammatory cytokines IL-1 β, NO and TNF-α. Furthermore, cell line studies in HCECs (human corneal epithelial cells) showed cytocompatibility and a dose-dependent uptake of ADHA NPs. ADHA NPs also maintained the cell integrity against 0.005% benzalkonium chloride (BAC) induced dry eye model on HCECs. Further, the Schirmer tear test showed twofold enhanced tear production in the developed formulation, and ADHA NPs seem to maintain the uniform structure of the tear. In vivo, drug retention studies ensured the good retention properties of ADHA NPs up to 12 h. In conclusion, ADHA NPs, because of their anti-inflammatory, mucoadhesiveness, modified drug release capacity, and higher drug retention properties, could serve as a potential therapeutic alternative for treating dry eye conditions.

Graphical Abstract

含地塞米松的生物氨基酸交联透明质酸纳米颗粒治疗干眼症
眼屏障、滞留时间差和频繁眼液抑制地塞米松的活性。精氨酸(Arg)和透明质酸(HA)对维持眼部健康至关重要,因为它们具有独特的生物学益处。在这项研究中,我们研究了精氨酸的阳离子性质,以开发地塞米松负载的HA纳米颗粒(ADHA NPs),并通过各种体外和体内技术评估其缓解干眼综合征的治疗潜力。采用离子交联法制备了ADHA NPs。ADHA NPs 6 h释药率接近94.99±4.16%,符合Korsemeyar-Peppas动力学模型(R2 = 0.9811)。此外,该配方具有较高的保水性(86.89±1.41%),并具有增强的黏附特性。与地塞米松相比,ADHA NPs在lps诱导的RAW 264.7细胞系中对促炎细胞因子IL-1 β、NO和TNF-α也表现出显著的抗炎作用(p < 0.001)。此外,HCECs(人角膜上皮细胞)的细胞系研究显示细胞相容性和ADHA NPs的剂量依赖性摄取。ADHA NPs对0.005%苯扎氯铵(BAC)诱导的HCECs干眼模型也能保持细胞完整性。此外,Schirmer撕裂测试显示,在开发的配方中,撕裂产量增加了两倍,ADHA NPs似乎保持了撕裂的均匀结构。在体内,药物保留研究确保ADHA NPs具有长达12小时的良好保留特性。总之,由于ADHA NPs具有抗炎、黏附性、改良的药物释放能力和更高的药物保留特性,可以作为治疗干眼症的潜在治疗方案。图形抽象
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来源期刊
AAPS PharmSciTech
AAPS PharmSciTech 医学-药学
CiteScore
6.80
自引率
3.00%
发文量
264
审稿时长
2.4 months
期刊介绍: AAPS PharmSciTech is a peer-reviewed, online-only journal committed to serving those pharmaceutical scientists and engineers interested in the research, development, and evaluation of pharmaceutical dosage forms and delivery systems, including drugs derived from biotechnology and the manufacturing science pertaining to the commercialization of such dosage forms. Because of its electronic nature, AAPS PharmSciTech aspires to utilize evolving electronic technology to enable faster and diverse mechanisms of information delivery to its readership. Submission of uninvited expert reviews and research articles are welcomed.
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