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

Author(s):  
Alejandro Sosnik ◽  
Ronya Ben Shabo ◽  
Hen Moshe Halamish

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.

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2142
Author(s):  
Alejandro Sosnik ◽  
Ronya Ben Shabo ◽  
Hen Moshe Halamish

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.


Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4496 ◽  
Author(s):  
Inbar Schlachet ◽  
Hen Moshe Halamish ◽  
Alejandro Sosnik

Intranasal (i.n.) administration became an alternative strategy to bypass the blood–brain barrier and improve drug bioavailability in the brain. The main goal of this work was to preliminarily study the biodistribution of mixed amphiphilic mucoadhesive nanoparticles made of chitosan-g-poly(methyl methacrylate) and poly(vinyl alcohol)-g-poly(methyl methacrylate) and ionotropically crosslinked with sodium tripolyphosphate in the brain after intravenous (i.v.) and i.n. administration to Hsd:ICR mice. After i.v. administration, the highest nanoparticle accumulation was detected in the liver, among other peripheral organs. After i.n. administration of a 10-times smaller nanoparticle dose, the accumulation of the nanoparticles in off-target organs was much lower than after i.v. injection. In particular, the accumulation of the nanoparticles in the liver was 20 times lower than by i.v. When brains were analyzed separately, intravenously administered nanoparticles accumulated mainly in the “top” brain, reaching a maximum after 1 h. Conversely, in i.n. administration, nanoparticles were detected in the “bottom” brain and the head (maximum reached after 2 h) owing to their retention in the nasal mucosa and could serve as a reservoir from which the drug is released and transported to the brain over time. Overall, results indicate that i.n. nanoparticles reach similar brain bioavailability, though with a 10-fold smaller dose, and accumulate in off-target organs to a more limited extent and only after redistribution through the systemic circulation. At the same time, both administration routes seem to lead to differential accumulation in brain regions, and thus, they could be beneficial in the treatment of different medical conditions.


Polymer ◽  
1994 ◽  
Vol 35 (14) ◽  
pp. 3122-3126 ◽  
Author(s):  
Yingming Yao ◽  
Lizhi Liu ◽  
Hong Li ◽  
Tianru Fang ◽  
Enle Zhou

2019 ◽  
Vol 553 ◽  
pp. 512-523 ◽  
Author(s):  
Hen Moshe Halamish ◽  
Jiří Trousil ◽  
Dmytro Rak ◽  
Kenneth D. Knudsen ◽  
Ewa Pavlova ◽  
...  

e-Polymers ◽  
2005 ◽  
Vol 5 (1) ◽  
Author(s):  
Vladimir Pavelka ◽  
Josef Jancar ◽  
Eva Nezbedova

AbstractThis paper reports on the relationship between structure and mechanical properties of poly(methyl methacrylate) (PMMA) reinforced with randomly oriented short poly(vinyl alcohol) (PVA) fibres. Special focus was on the effect of fibre content on the impact resistance of PMMA/PVA composites. Instrumented Charpy impact tests were carried out to characterize the impact resistance of PMMA/PVA composites. Linear elastics fracture mechanics was used to determine the dynamic critical strain energy release rate (GId) and the critical stress intensity factor (KId). Fracture surfaces were observed using scanning electron microscopy (SEM). Dynamic mechanical analysis was carried out to describe the viscoelastic response of the material. Finally, the behaviour of PMMA/PVA composites was interpreted using current short-fibre composite models. It was shown that a small amount of added PVA fibres (0.42 - 1.68 vol.-%) led to an increase of elastic modulus and yield stress under impact conditions. GId was also slightly increased, but KId remained unchanged. Good agreement was found between SEM observations and fracture toughness measured under impact loading.


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