Key Transdermal Patch Using Cannabidiol-Loaded Nanocarriers with Better Pharmacokinetics in vivo

Abstract

Purpose

Cannabidiol (CBD) is a promising therapeutic drug with low addictive potential and a favorable safety profile. However, CBD did face certain challenges, including poor solubility in water and low oral bioavailability. To harness the potential of CBD by combining it with a transdermal drug delivery system (TDDS). This innovative approach sought to develop a transdermal patch dosage form with micellar vesicular nanocarriers to enhance the bioavailability of CBD, leading to improved therapeutic outcomes.

Methods

A skin-penetrating micellar vesicular nanocarriers, prepared using nano emulsion method, cannabidiol loaded transdermal nanocarriers-12 (CTD-12) was presented with a small particle size, high encapsulation efficiency, and a drug-loaded ratio for CBD. The skin permeation ability used Strat-M™ membrane with a transdermal diffusion system to evaluate the CTD and patch of CTD-12 (PCTD-12) within 24 hrs. PCTD-12 was used in a preliminary pharmacokinetic study in rats to demonstrate the potential of the developed transdermal nanocarrier drug patch for future applications.

Results

In the transdermal application of CTD-12, the relative bioavailability of the formulation was 3.68 ± 0.17-fold greater than in the free CBD application. Moreover, PCTD-12 indicated 2.46 ± 0.18-fold higher relative bioavailability comparing with free CBD patch in the ex vivo evaluation. Most importantly, in the pharmacokinetics of PCTD-12, the relative bioavailability of PCTD-12 was 9.47 ± 0.88-fold higher than in the oral application.

Conclusion

CTD-12, a transdermal nanocarrier, represents a promising approach for CBD delivery, suggesting its potential as an effective transdermal dosage form.

Graphical Abstract

Keywords:

• cannabidiol
• pharmacokinetics
• transdermal
• nano emulsion
• drug patch
• nanocarrier

Abbreviations

CBD, cannabidiol; EE%, encapsulation efficiency; DL%, drug-loaded ratio; THC, tetrahydrocannabinol; TDDS, transdermal drug delivery system; SNEDDS, self-nanoemulsifying drug delivery systems; SLN, solid lipid nanoparticles; NLCs, nanostructured lipid carriers; DLS, dynamic light scattering; DAD, diode array detector; Oral, oral route; IV, intravenous injection; SRM, single reaction monitoring mode; PDI, Polydisperse Index; TD-NCs, Transdermal nanocarriers; CTD, Cannabidiol loaded transdermal nanocarriers; AUC_0-24hr, area under the curve-time curve from 0 to 24-hour time point; Flux_0-24hr, flux-time curve from 0 to 24-hour time point; FA, formulation bioavailability; BA, bioavailability; PCTD, patch of cannabidiol loaded transdermal nanocarriers.

Data Sharing Statement

The raw/processed data required to reproduce these findings cannot be shared at this time due to legal or ethical reasons.

Ethics Statements

The animal study was conducted according to the guidelines of the Animal Care Committee of the National Chung Hsing University and approved by the Committee (IACUC No. 111-127) and performed in accordance with the National Research Council’s Guide for the Care and Use of Laboratory Animals.

Acknowledgments

This research was supported by grants from the Powin Biomedical Co., Ltd. of the Republic of China (R.O.C).

Disclosure

The authors declare no conflicts of interest.

Additional information

Funding

This research was funded by the Powin Biomedical Co., Ltd.