ArticlePharmaceutical research2025
Enhancing Cannabidiol Apparent Solubility and Oral Delivery: Self-assembled Nanomicelles of Amphiphilic Block Copolymer with γ-Polyglutamic Acid-grafted Cholesterol.
Article in Pharmaceutical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
7 authors.
Funding
Abstract
purposeCannabidiol (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.
methodsThe 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.
resultsThe 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 C
conclusionsThese 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.
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Registered trials
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