Aqueous cannabidiol β-cyclodextrin complexed polymeric micelle nasal spray to attenuate in vitro and ex vivo SARS-CoV-2-induced cytokine storms

Copyright © 2023 Elsevier B.V. All rights reserved..

Cannabidiol (CBD) has a number of biological effects by acting on the cannabinoid receptors CB1 and CB2. CBD may be involved in anti-inflammatory processes via CB1 and CB2 receptors, resulting in a decrease of pro-inflammatory cytokines. However, CBD's poor aqueous solubility is a major issue in pharmaceutical applications. The aim of the present study was to develop and evaluate a CBD nasal spray solution. A water-soluble CBD was prepared by complexation with β-cyclodextrin (β-CD) at a stoichiometric ratio of 1:1 and forming polymeric micelles using poloxamer 407. The mixture was then lyophilized and characterized using FT-IR, DSC, and TGA. CBD-β-CD complex-polymeric micelles were formulated for nasal spray drug delivery. The physicochemical properties of the CBD-β-CD complex-polymeric micelle nasal spray solution (CBD-β-CDPM-NS) were assessed. The results showed that the CBD content in the CBD-β-CD complex polymeric micelle powder was 102.1 ± 0.5% labeled claim. The CBD-β-CDPM-NS was a clear colorless isotonic solution. The particle size, zeta potential, pH value, and viscosity were 111.9 ± 0.7 nm, 0.8 ± 0.1 mV, 6.02 ± 0.02, and 12.04 ± 2.64 cP, respectively. This formulation was stable over six months at ambient temperature. The CBD from CBD-β-CDPM-NS rapidly released to 100% within 1 min. Ex vivo permeation studies of CBD-β-CDPM-NS through porcine nasal mucosa revealed a permeation rate of 4.8 μg/cm2/min, which indicated that CBD was effective in penetrating nasal epithelial cells. CBD-β-CDPM-NS was tested for its efficacy and safety in terms of cytokine production from nasal immune cells and toxicity to nasal epithelial cells. The CBD-β-CDPM-NS was not toxic to nasal epithelial at the concentration of CBD equivalent to 3.125-50 μg/mL. When the formulation was subjected to bioactivity testing against monocyte-like macrophage cells, it proved that the CBD-β-CDPM-NS has the potential to inhibit inflammatory cytokines. CBD-β-CDPM-NS demonstrated the formulation's ability to reduce the cytokine produced by S-RBD stimulation in ex vivo porcine nasal mucosa in both preventative and therapeutic modes.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:640

Enthalten in:

International journal of pharmaceutics - 640(2023) vom: 10. Juni, Seite 123035

Sprache:

Englisch

Beteiligte Personen:

Changsan, Narumon [VerfasserIn]
Sawatdee, Somchai [VerfasserIn]
Suedee, Roongnapa [VerfasserIn]
Chunhachaichana, Charisopon [VerfasserIn]
Srichana, Teerapol [VerfasserIn]

Links:

Volltext

Themen:

β-Cyclodextrin
19GBJ60SN5
Beta-Cyclodextrins
Cannabidiol
Journal Article
Micelles
Nasal Sprays
Nasal spray solution
Polymeric micelles
Pro-inflammatory cytokine
SARS-CoV-2

Anmerkungen:

Date Completed 29.05.2023

Date Revised 29.05.2023

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.ijpharm.2023.123035

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM356855570