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<p>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 <i>in-vitro</i> and <i>in-vivo</i> 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&#xa0;h and followed the Korsemeyar-Peppas kinetic model (R<sup>2</sup> = 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 (<i>p</i> &lt; 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. <i>In vivo,</i> drug retention studies ensured the good retention properties of ADHA NPs up to 12&#xa0;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.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 发表日期：

    2025年3月27日

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  • 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

摘要

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