Scholarlink

Purpose <p>The study assessed dual-modified liposomes for delivering pApoE2 and pGFP across an <i>in vitro</i> blood–brain barrier (BBB) model supplemented with hydrocortisone (HC), evaluating their transfection efficiency in neuronal cells across the BBB and the impact of hydrocortisone on BBB integrity.</p> Methods <p>An <i>in vitro</i> BBB model was developed using brain endothelial cells (bEnd.3) co-cultured with primary astrocytes in a transwell system. Hydrocortisone's effect on BBB integrity was assessed via transepithelial electrical resistance (TEER), permeability and transport studies. Liposomes, modified with cell-penetrating peptide-RDP and Transferrin, encapsulating pApoE2 or pGFP-chitosan polyplex, were evaluated for neuronal cell transfection after crossing the BBB<b>.</b></p> Results <p>The BBB models supplemented with 150&#xa0;nM HC showed a significant increase in TEER values compared to monolayers (<i>p</i> &lt; 0.0001) and co-culture BBB models without HC supplementation (<i>p</i> &lt; 0.01), indicating enhanced BBB integrity. Permeability assays demonstrated reduced sodium fluorescein translocation across the 150&#xa0;nM hydrocortisone-supplemented BBB models compared to monolayers (<i>p</i> &lt; 0.001) and co-culture models without HC supplementation (<i>p</i> &lt; 0.05). Liposomes exhibited good characteristics and efficient encapsulation of pApoE2 or pGFP-chitosan polyplex, and successfully crossed the developed BBB model. Dual-modified liposomes (RDP-T<sub>f</sub>) achieved significantly greater transfection efficiency of pApoE2 and pGFP in neuronal cells (<i>p</i> &lt; 0.0001) compared to single-modified (RDP or T<sub>f</sub>) and plain liposomes.</p> Conclusions <p>Hydrocortisone enhanced the BBB properties of the <i>in vitro</i> model, making it more representative of the <i>in vivo</i> BBB. Dual-modified liposomes demonstrated superior efficacy in delivering genetic materials across the BBB, providing a promising approach for therapeutic interventions in neurodegenerative diseases like Alzheimer’s.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Dual-modified Liposomes Encapsulating Nucleic Acids (pApoE2 or pGFP) for Transport Studies Across a Hydrocortisone-enhanced In Vitro Blood–brain Barrier Model for CNS Therapeutic Screening

  • 期刊论文

  • 发表日期：

    2025年7月28日

查看全文
  • Chinenye Edith Muolokwu,
  • Avinash Gothwal,
  • Takahisa Kanekiyo,
  • Jagdish Singh

摘要

Purpose

The study assessed dual-modified liposomes for delivering pApoE2 and pGFP across an in vitro blood–brain barrier (BBB) model supplemented with hydrocortisone (HC), evaluating their transfection efficiency in neuronal cells across the BBB and the impact of hydrocortisone on BBB integrity.

Methods

An in vitro BBB model was developed using brain endothelial cells (bEnd.3) co-cultured with primary astrocytes in a transwell system. Hydrocortisone's effect on BBB integrity was assessed via transepithelial electrical resistance (TEER), permeability and transport studies. Liposomes, modified with cell-penetrating peptide-RDP and Transferrin, encapsulating pApoE2 or pGFP-chitosan polyplex, were evaluated for neuronal cell transfection after crossing the BBB.

Results

The BBB models supplemented with 150 nM HC showed a significant increase in TEER values compared to monolayers (p < 0.0001) and co-culture BBB models without HC supplementation (p < 0.01), indicating enhanced BBB integrity. Permeability assays demonstrated reduced sodium fluorescein translocation across the 150 nM hydrocortisone-supplemented BBB models compared to monolayers (p < 0.001) and co-culture models without HC supplementation (p < 0.05). Liposomes exhibited good characteristics and efficient encapsulation of pApoE2 or pGFP-chitosan polyplex, and successfully crossed the developed BBB model. Dual-modified liposomes (RDP-Tf) achieved significantly greater transfection efficiency of pApoE2 and pGFP in neuronal cells (p < 0.0001) compared to single-modified (RDP or Tf) and plain liposomes.

Conclusions

Hydrocortisone enhanced the BBB properties of the in vitro model, making it more representative of the in vivo BBB. Dual-modified liposomes demonstrated superior efficacy in delivering genetic materials across the BBB, providing a promising approach for therapeutic interventions in neurodegenerative diseases like Alzheimer’s.

Graphical Abstract