Nanocomposite Cryogel Carriers from 2-Hydroxyethyl Cellulose Network and Cannabidiol-Loaded Polymeric Micelles for Sustained Topical Delivery

Abstract

In this contribution, we report the development of original nanocomposite cryogels for sustained topical delivery of hydrophobic natural active substances such as cannabidiol (CBD). The cryogels were fabricated by a method involving cryogenic treatment and photo-crosslinking of aqueous systems containing biodegradable 2-hydroxyethyl cellulose (HEC) and CBD-loaded polymeric micelles. The preparation of the water-soluble form of CBD was a key element for the successful drug loading in the one-pot reaction. The main physical, mechanical and biological characteristics of CBD-loaded and blank cryogels such as gel fraction yield, swelling degree, morphology, storage and loss moduli, and cytotoxicity were studied in detail. The advantage of nanocomposite over pure HEC cryogel carriers in terms of achieving a sustained release profile was also demonstrated.

Polysaccharide Cryogels Containing β-Cyclodextrin for the Delivery of Cannabidiol

“…Overall, the combination of embedded (in the cavities) and adsorbed (on the inner surface) CBD afforded a bi-phasic release behavior-initial burst release in the first 3 hours followed by slower drug release. Such behavior can be beneficial in the treatment of cutaneous neoplastic diseases and, unlike the systems exhibiting delayed-release only [15], can provide prompt exposure of malignant cells to the initially released CBD and sustained inhibitory activity. Both free CBD and formulated CBD exhibited concentration-dependent cytotoxicity.…”

“…On the other hand, G raised proportionally with the increase in β-CD fraction into the polymer network (Figure 4B). Thus, an obvious reinforcing effect of β-CD (approximately 2.5 times) was found as compared to the pure HEC and HEC nanocomposite cryogels, containing polymer micelles [15]. The viscoelastic properties of HEC/β-CD cryogels were assessed by dynamic rheological measurements.…”

“…This gap is certainly not insurmountable with conventional drug delivery platforms and dosing schedules. On these grounds, numerous drug delivery systems for cannabidiol based on nanocarriers or nanocomposite materials, such as self-emulsifying systems, nano-spheres, micelles, and inclusion complexes have been developed [11][12][13][14][15][16]. Since the oral route of administration for CBD has been associated with poor bioavailability, other more effective routes for sustained therapeutic delivery of CBD have been evaluated.…”

“…However, there is limited literature available about the topical/transdermal delivery of CBD intended for skin cancer treatment. Very recently, we have reported on a nanocomposite system based on CBD-loaded polymeric micelles, embedded in a hydroxyethyl cellulose cryogel matrix [15]. Such cryogel-based drug delivery systems are considered beneficial for the sustained local delivery of CBD to patients with CTCL.…”

Cryogel Carriers Comprising β‐Cyclodextrin Moieties for Improved Solubilization and Delivery of Aripiprazole

“…Nanocomposite cryogels based on cellulose derivatives and core–shell micelles were developed for delivery of curcumin and cannabidiol. [ 12,13 ] The incorporation of hydrophobic micellar domains in the hydrogel matrix was found essential for the efficient solubilization and sustained release of the drugs. In another approach, β‐cyclodextrin moieties, covalently attached to the hydrophilic dextran network, were exploited for loading the cryogel carrier with curcumin via “host‐guest” complexation.…”