Cannabidiol-Loaded Mixed Polymeric Micelles of Chitosan/Poly(Vinyl Alcohol) and Poly(Methyl Methacrylate) for Trans-Corneal Delivery

Ocular drug delivery is challenging due to the very short drug residence time and low permeability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan (CS) and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD), an anti-inflammatory cannabinoid. CBD-loaded mixed PMs are physically stabilized by ionotropic crosslinking of the CS domains with sodium tripolyphoshate and spray-drying. These mixed PMs display CBD loading capacity of 20% w/w and sizes of 100–200 nm, and spherical morphology (cryogenic-transmission electron microscopy). The good compatibility of the unloaded and CBD-loaded PMs is assessed in a human corneal epithelial cell line. Then, we confirm the permeability of CBD-free PMs and nanoencapsulated CBD in human corneal epithelial cell monolayers under liquid–liquid and air–liquid conditions. Overall, our results highlight the potential of these polymeric nanocarriers for ocular drug delivery.

Cannabidiol-Loaded Mixed Polymeric Micelles of Chitosan/Poly(Vinyl Alcohol) And Poly(Methyl Methacrylate) For Trans-Corneal Delivery

Ocular drug delivery is one of the most challenging administration routes due to the very low drug bioavailability. In this work, we produce and characterize mucoadhesive mixed polymeric micelles (PMs) made of chitosan and poly(vinyl alcohol) backbones graft-hydrophobized with short poly(methyl methacrylate) blocks and use them to encapsulate cannabidiol (CBD), an anti-inflammatory cannabinoid. CBD-loaded mixed PMs are physically stabilized by ionotropic crosslinking of the CS domains with sodium tripolyphoshate and spray-drying. These mixed PMs display CBD loading capacity of 20% w/w and sizes of 100-200 nm, and spherical morphology (cryogenic-transmission electron microscopy). The good compatibility of the unloaded and CBD-loaded PMs is assessed in a human corneal epithelial cell line. Then, we confirm the permeability of CBD-free PMs and nanoencapsulated CBD in cornea cell monolayers under liquid-liquid and air-liquid conditions. Overall, our results highlight the potential of these polymeric nanocarriers for ocular drug delivery.

Enhanced Oral Absorption of Icaritin by Using Mixed Polymeric Micelles Prepared with a Creative Acid-Base Shift Method

The purpose of this study was to develop mixed polymeric micelles with high drug loading capacity to improve the oral bioavailability of icaritin with Soluplus® and Poloxamer 407 using a creative acid-base shift (ABS) method, which exhibits the advantages of exclusion of organic solvents, high drug loading and ease of scaling-up. The feasibility of the ABS method was successfully demonstrated by studies of icaritin-loaded polymeric micelles (IPMs). The prepared IPMs were characterized to have a spherical shape with a size of 72.74 ± 0.51 nm, and 13.18% drug loading content. In vitro release tests confirmed the faster release of icaritin from IPMs compared to an oil suspension. Furthermore, bioavailability of icaritin in IPMs in beagle dogs displayed a 14.9-fold increase when compared with the oil suspension. Transcellular transport studies of IPMs across Caco-2 cell monolayers confirmed that the IPMs were endocytosed in their intact forms through macropinocytosis, clathrin-, and caveolae-mediated pathways. In conclusion, the results suggested that the mixed micelles of Soluplus® and Poloxamer 407 could be a feasible drug delivery system to enhance oral bioavailability of icaritin, and the ABS method might be a promising technology for the preparation of polymeric micelles to encapsulate poorly water-soluble weakly acidic and alkaline drugs.

DPD Simulations on Mixed Polymeric DOX-loaded Micelles Assembled from PCL-SS-PPEGMA/ PDEA-PPEGMA and Their Dual pH/Reduction-responsive Release

Mixed polymeric micelles by combination of two or more dissimilar polymers is a potential strategy to achieve multiple stimuli-response for anti-cancer drug delivery. However, their drug loading co-micellization behavior and...

Fabrication of Mixed Polymeric Micelles Based on Stimuli-Responsive Amphiphilic Copolymers for Drug Delivery and Controlled Release

In this report, mixed polymeric micelles (MPMs) system self-assembled from two kinds of cholesterol-grafted amphiphilic block copolymers cholesterol modified poly ([Formula: see text]-amino esters)-grafted disulfide poly (ethylene glycol) methyl ether (PAE(-ss-mPEG)-[Formula: see text]-Chol) and poly([Formula: see text]-amino ester)-g-poly(ethylene glycol) methyl ether-cholesterol (PAE-[Formula: see text]-mPEG-Chol) were prepared for drug delivery and controlled release with pH and redox-responsibilities. The self-assembly of two block copolymers was evaluated by measurement of critical micelle concentration (CMC) values using fluorescence spectroscopy. The hydrodynamic diameter, polydispersity index (PDI) and zeta-potential of MPMs in aqueous were recorded by dynamic light scattering (DLS) at different conditions. Doxorubicin (DOX) was efficiently encapsulated in the micellar core by the hydrophobic interaction. The drug loading content (LC) and encapsulation efficacy (EE) of MPMs with different formulations were evaluated. The DOX was released due to the swelling and disassembly of MPMs induced by low pH and high glutathione (GSH) concentrations. The in vitro results demonstrated that drug release rate and cumulative release were obviously dependent on pH values and reducing agents. The results showed that the MPMs could be the potential anticancer drug delivery carriers with pH/redox-triggered drug release profile.