Cinnamyl-Modified Polyglycidol/Poly(ε-Caprolactone) Block Copolymer Nanocarriers for Enhanced Encapsulation and Prolonged Release of Cannabidiol

Abstract

The present study describes the development of novel block copolymer nanocarriers of the phytocannabinoid cannabidiol (CBD), designed to enhance the solubility of the drug in water while achieving high encapsulation efficiency and prolonged drug release. Firstly, a well-defined amphiphilic block copolymer consisting of two outer hydrophilic polyglycidol (PG) blocks and a middle hydrophobic block of poly(ε-caprolactone) bearing pendant cinnamyl moieties (P(CyCL-co-CL)) were synthesized by the click coupling reaction of PG-monoalkyne and P(CyCL-co-CL)-diazide functional macroreagents. A non-modified polyglycidol/poly(ε-caprolactone) amphiphilic block copolymer was obtained as a referent system. Micellar carriers based on the two block copolymers were formed via the solvent evaporation method and loaded with CBD following two different protocols—loading during micelle formation and loading into preformed micelles. The key parameters/characteristics of blank and CBD-loaded micelles such as size, size distribution, zeta potential, molar mass, critical micelle concentration, morphology, and encapsulation efficiency were determined by using dynamic and static multiangle and electrophoretic light scattering, transmission electron microscopy, and atomic force microscopy. Embedding CBD into the micellar carriers affected their hydrodynamic radii to some extent, while the spherical morphology of particles was not changed. The nanoformulation based on the copolymer bearing cinnamyl moieties possessed significantly higher encapsulation efficiency and a slower rate of drug release than the non-modified copolymer. The comparative assessment of the antiproliferative effect of micellar CBD vs. the free drug against the acute myeloid leukemia-derived HL-60 cell line and Sezary Syndrome HUT-78 demonstrated that the newly developed systems have pronounced antitumor activity.

How Biodegradable Polymers Can be Effective Drug Delivery Systems for Cannabinoids? Prospectives and Challenges

“… HL-60 and HUT-78 Against HL-60: IC 50 = 3.00 µg/mL Against HUT-78: IC 50 = 8.30 µg/mL - - - - CBD was loaded during micelle formation. [ 247 ] Micelles CBD Cinnamyl modified polyglycolidol/PCL PG 50 - b -PPO 4 - b -[P(CyCL) 4 - co -(CL) 40 ]- b- PPO 4 - b- PG 50 57.0 ± 1.4 nm ζ = 4.19 ± 2.50 mV EE = 92.0% In PBS pH 7.4: about 40% of the drug was released within 24h. HL-60 and HUT-78 Against HL-60: IC 50 = 3.20 µg/mL Against HUT-78: IC 50 = 8.00 µg/mL - - - - CBD was loaded into preformed micelles.…”

“… HL-60 and HUT-78 Against HL-60: IC 50 = 2.29 µg/mL Against HUT-78: IC 50 = 5.17 µg/mL - - - - CBD was loaded into preformed micelles. [ 247 ] Nanoemulsion (NE)-filled hydrogel CBD CS Droplet size 1 mg CBD/g of NE: 126 ± 3 nm 5 mg CBD/g of NE: 102 ± 3 nm - WS1 MTT assay has not shown any changes in cell viability and cytotoxicity at a concentration of 0.5 to 1.5 mg/mL. - - - - Ex vivo skin penetration parameters: For NE: Steady-state flux - 403.37 ± 130.09 µg/cm 2 h −1 Q 30h = 572.56 ± 211.11 µg/cm 2 Permeation coefficient - 80.67 ± 211.11 mg/cm 2 h For NE-filled hydrogel: Steady-state flux - 475.68 ± 162.57 µg/cm 2 h −1 Q 30h = 709.22 ± 220.62 µg/cm 2 Permeation coefficient - 95.14 ± 32.51 mg/cm 2 h. Tape stripping experiments: For NE: Total amount of CBD recovered in the stratum corneum - 3853.20 ± 543.06 ng/cm 2 Achieved penetration depth - 10.493 ± 3.958 µm For NE-filled hydrogel: Total amount of CBD recovered in the stratum corneum - 2745.41 ± 1022.44 ng/cm 2 Achieved penetration depth - 14.644 ± 8.338 µm [ 248 ] Nanoparticles (NPs) CB13 PLGA Particle size within range 253–344 nm EE ~ 70% Strongly negative ζ In PBS pH 7.4: about 60% of the drug was released within 15 days.…”

Development, Characterization and Pharmacological Evaluation of Cannabidiol-Loaded Long Circulating Niosomes

“…6%) after oral/oromucosal administration [22], which directs research efforts to explore other routes of administration or to develop nanoscale drug delivery systems for successful CBD delivery. Various nanocarriers such as nanoemulsion, polymer coated nanoparticles [23], transfersomes [24], nanostructured lipid carriers [25], polymeric micelles [26,27], liposomes [28,29], and ethosomes [30] have been already reported as effective CBD delivery platforms. However, liposomal carriers suffer from some disadvantages in terms of systemic delivery, such as low CBD encapsulation efficiency and short halflife; therefore, our paper provides an alternative technological approach in terms of both CBD entrapment and drug delivery carrier.…”