ABSTRACT
Cannabidiol (CBD) is a natural terpenophenolic compound with known pharmacological activities, but the poor solubility of CBD in water limits its widespread use in medicine and pharmacy. Polymeric (nano)carriers demonstrated high potential for enhancing the solubility and therapeutic activity of lipophilic drugs such as CBD. Here, we report the elaboration of a novel hydroxypropyl cellulose (HPC)-based in situ gelling formulation for controlled delivery of CBD. In the first stage, nanosized polymeric micelles from poly(ethylene oxide)-block-poly(α-cinnamyl-ε-caprolactone-co-ε-caprolactone) (PEO-b-P(CyCL-co-CL) diblock copolymers) were used to increase the solubility of CBD in water. Different copolymers were assessed, and the carrier with the highest encapsulation efficiency (EE) and drug loading capacity (DLC) was selected for further elaboration of nanocomposite in situ gel formulations. Next, the sol-to-gel transition behavior of HPC as a function of K2SO4 concentration in the aqueous solution was investigated by microcalorimetry and dynamic oscillatory rheology, and the optimal formulation capable of forming a physical gel under physiological conditions was determined. Finally, injectable nanocomposite hydrogels comprising cannabidiol were fabricated, and their drug release profile and cytotoxicity against human tumor cell lines were evaluated. The in situ gels exhibited prolonged drug release over 12 h, controlled by gel erosion, and the cytotoxicity of formulated cannabidiol was comparable with that of a free drug.
Subject(s)
Cannabidiol , Micelles , Humans , Polymers/chemistry , Drug Delivery Systems , Polyethylene Glycols/chemistry , Gels , Water , Drug Carriers , Polyesters/chemistryABSTRACT
Cannabidiol (CBD) has attracted increasing interest due to its therapeutic potential for treating numerous diseases. However, CBD is very lipophilic and has very unfavorable pharmacokinetics and low bioavailability. Efforts are focused on developing drug delivery systems for enhanced solubilization and therapeutic activity of CBD. Here, we report the preparation of original super-macroporous cryogels from 2-hydroxyethyl cellulose (HEC) and ß-cyclodextrin (ß-CD) designed for the topical delivery of CBD. The cryogels were synthesized by photochemical crosslinking in a frozen aqueous system, purified, and then loaded with CBD. The effect of HEC/ß-CD mass ratio (100:0; 50:50; 40:60 and 20:80) in the reaction mixture on the reaction efficiency, physico-mechanical properties of cryogels, drug release profile, and antineoplastic potential were evaluated in detail. The cryogels showed a bi-phasic release behavior: initial burst release in the first 3 hours followed by slower drug release which can be beneficial in the treatment of cutaneous neoplastic diseases.
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.
