Scholarlink

Purpose <p>Cannabidiol (CBD) exhibits antiepileptic, anticonvulsant, and anticancer effects. However, its clinical value is limited by poor oral absorption, low water solubility, and poor stability. Therefore, this study aimed to prepare a novel nanomicelles (NMs) to improve the above aspects of CBD.</p> Methods <p>The amphiphilic polymer was synthesized by selecting γ -polyglutamic acid (γ-PGA) and cholesterol (CHOL) as hydrophilic and hydrophobic materials respectively. The optimal preparation process for CBD/(γ-PGA-g-CHOL) NMs was obtained through single-factor and orthogonal tests. The particle size, potential, stability, morphology, apparent solubility and <i>in vitro</i> drug release behavior of the drug-loaded NMs were characterized. Cytotoxicity, uptake and transport experiments on Caco-2 cells and <i>in vivo</i> pharmacokinetics studies in rats were performed for <i>in vitro</i> and <i>in vivo</i> oral absorption of the drugs.</p> Results <p>The optimal parameters were a dosage of 2&#xa0;mg, blank NM concentration of 5&#xa0;mg/mL, an organic/aqueous ratio of 1:5, and a stirring time of 6&#xa0;h. The NMs showed pH-sensitive release behavior, with particle size 163.1 ± 2.3&#xa0;nm, zeta potential -16.5 ± 1.7&#xa0;mV, encapsulation rate 84.46% ± 0.35%, and drug loading 8.78% ± 0.28%. They were spherical by SEM, stable at 25 ℃ and 37 ℃, and their apparent solubility increased 424-fold. The NMs were biocompatible and improved CBD absorption in uptake/transport tests. Orally administered NMs showed lower apparent clearance value (CL/F), and higher C<sub>max</sub> and AUC than those in the free CBD group.</p> Conclusions <p>These findings reveal potential of the delivery system, γ-PGA-g-CHOL NMs, to improve the stability of CBD and enhance its apparent solubility and systemic exposure.</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

Enhancing Cannabidiol Apparent Solubility and Oral Delivery: Self-assembled Nanomicelles of Amphiphilic Block Copolymer with γ-Polyglutamic Acid-grafted Cholesterol

  • 期刊论文

  • 发表日期：

    2025年10月1日

查看全文
  • Rui Li,
  • Wenhui Ruan,
  • Liyan Lu,
  • Zhijuan Wu,
  • Rui Hao,
  • Yingli Wang,
  • Jue Chen

摘要

Purpose

Cannabidiol (CBD) exhibits antiepileptic, anticonvulsant, and anticancer effects. However, its clinical value is limited by poor oral absorption, low water solubility, and poor stability. Therefore, this study aimed to prepare a novel nanomicelles (NMs) to improve the above aspects of CBD.

Methods

The amphiphilic polymer was synthesized by selecting γ -polyglutamic acid (γ-PGA) and cholesterol (CHOL) as hydrophilic and hydrophobic materials respectively. The optimal preparation process for CBD/(γ-PGA-g-CHOL) NMs was obtained through single-factor and orthogonal tests. The particle size, potential, stability, morphology, apparent solubility and in vitro drug release behavior of the drug-loaded NMs were characterized. Cytotoxicity, uptake and transport experiments on Caco-2 cells and in vivo pharmacokinetics studies in rats were performed for in vitro and in vivo oral absorption of the drugs.

Results

The optimal parameters were a dosage of 2 mg, blank NM concentration of 5 mg/mL, an organic/aqueous ratio of 1:5, and a stirring time of 6 h. The NMs showed pH-sensitive release behavior, with particle size 163.1 ± 2.3 nm, zeta potential -16.5 ± 1.7 mV, encapsulation rate 84.46% ± 0.35%, and drug loading 8.78% ± 0.28%. They were spherical by SEM, stable at 25 ℃ and 37 ℃, and their apparent solubility increased 424-fold. The NMs were biocompatible and improved CBD absorption in uptake/transport tests. Orally administered NMs showed lower apparent clearance value (CL/F), and higher Cmax and AUC than those in the free CBD group.

Conclusions

These findings reveal potential of the delivery system, γ-PGA-g-CHOL NMs, to improve the stability of CBD and enhance its apparent solubility and systemic exposure.