Enhanced Skin Penetration of Cannabidiol Using Organosilane Particles as Transdermal Delivery Vehicles

Abstract

There is potential for cannabidiol to act as an analgesic, anxiolytic and antipsychotic active ingredient; however, there is a need to find alternate administration routes to overcome its low oral bioavailability. In this work, we propose a new delivery vehicle based on encapsulation of cannabidiol within organosilica particles as drug delivery vehicles, which are subsequently incorporated within polyvinyl alcohol films. We investigated the long-term stability of the encapsulated cannabidiol, as well as its release rate, in a range of simulated fluids with different characterization techniques, including Fourier Transform Infrared (FT-IR) and High-performance Liquid Chromatography (HPLC). Finally, we determined the transdermal penetration in an ex vivo skin model. Our results show that cannabidiol is stable for up to 14 weeks within polyvinyl alcohol films at a range of temperatures and humidity. Release profiles are first-order, consistent with a mechanism involving diffusion of the cannabidiol (CBD) out of the silica matrix. The silica particles do not penetrate beyond the stratum corneum in the skin. However, cannabidiol penetration is enhanced and is detected in the lower epidermis, which was 0.41% of the total CBD in a PVA formulation compared with 0.27% for pure CBD. This is partly due to an improvement of its solubility profile as it is released from the silica particles, but we cannot rule out effects of the polyvinyl alcohol. Our design opens a route for new membrane technologies for cannabidiol and other cannabinoid products, where administration via non-oral or pulmonary routes can lead to better outcomes for patient cohorts in a range of therapeutics.

Co-Dispersion Delivery Systems with Solubilizing Carriers Improving the Solubility and Permeability of Cannabinoids (Cannabidiol, Cannabidiolic Acid, and Cannabichromene) from Cannabis sativa (Henola Variety) Inflorescences

“…CBD, zein, and zein-WP nanoparticles showed lower sustained release during simulated gastric fluid. Pure CBD has a low solubility profile in both SIF and SGF, with less than 3% within 1 h and less than 10% of CBD released in 48 h [ 106 ]. CBD-Silica cast in PVA films show a significantly increased dissolution profile of SIF and SGF, with about 3–7% of CBD released in 1 h and about 40–45% of released CBD in 48 h. Poor solubility of CBD from hemp oil products like oral drops, capsules, and tablets in an acidic medium was also confirmed as 0% of CBD released in FaSSGF, besides one beverage enhancer [ 107 ].…”

Transdermal Delivery of Cannabidiol for the Management of Acute Inflammatory Pain: A Comprehensive Review of the Literature

“…A higher concentration of CBD is also measured below the SC when the formulation is incorporated in PVA films than with pure CBD, consistent with the enhanced dissolution profile. However, further optimization of the dose and transdermal penetration are required for this formulation to be successfully implemented [ 57 ].…”

Optical Methods for Non-Invasive Determination of Skin Penetration: Current Trends, Advances, Possibilities, Prospects, and Translation into In Vivo Human Studies

“…Dual labelling allows the determination of different substances measured sequentially in different excitation/emission fluorescence channels [ 89 , 95 ]. Thus, the depth-dependent accumulation of fluorescent substances, such as polystyrene fluorescein 5-isothiocyanate (FITC)-containing particles (excitation at 488 nm) [ 89 ], fluorescent polymeric nanoparticles (excitation at 488 nm) [ 96 ], rhodamine B base loaded with a phospholipid surfactant conjugated with a green fluorophore (excitation/emission at 493/517 and 577/603 nm) [ 95 ], Nile red in different vehicles (excitation/emission at 514/550 nm) [ 97 ], fluorescent model substances of increasing lipophilicity (excitation/emission at 488/514 and 564/574 nm) [ 98 ], liposomal formulation containing hydrophilic carboxyfluorescein (excitation/emission at 470/520 nm) [ 99 ], Cy7-loaded calcium carbonate particles (excitation/emission at 405/(420–490) nm) [ 100 ], quantum dot fluorescent nanoparticles of different modifications (excitation/emission at 488/565 nm) [ 101 ], nanodiamonds (excitation/emission at 532/(650–720) nm) [ 102 ], gold nanoparticles coated with a mixture of hydroxyl- and carboxyl-terminated thiolates (excitation at 485 and 543 nm) [ 103 ], the infrared-triggered release of FITC gold nanoparticle-doped bovine serum albumin (excitation/emission at 488/580 nm) [ 60 ], FITC-silica particles (excitation/emission at 488/(500–550) nm) [ 104 ], and curcumin [ 105 ] can be easily visualized in the skin, and the penetration depth and pathways can be determined. For example, using the FCLSM, the release of the fluorescent cytostatic chemotherapeutic drug doxorubicine with sweat on the skin surface and its subsequent penetration and accumulation in the SC of glabrous skin can be successfully determined [ 106 , 107 ].…”