Effect of Piperine Codelivery on the Oral Bioavailability of Cannabidiol: Insights from <i>In Vitro</i> Digestion and <i>In Vivo</i> Pharmacokinetics

High Resolution Image Download MS PowerPoint Slide This study investigated whether coencapsulation of cannabidiol (CBD) and piperine (PIP) in food-grade nanostructured lipid carriers (NLCs) enhances the CBD oral bioavailability. NLCs containing long-chain fatty acids were formulated with 1% CBD and 1% PIP using either a CBD isolate (CBD iso ) or a CBD extract (CBD ext ). Both systems showed high encapsulation efficiency and good stability over 28 days, with similar physicochemical properties. However, the CBD form strongly influenced digestion behavior: NLC-PIP-CBD iso exhibited high bioaccessibility for CBD (87 ± 5%), while NLC-PIP-CBD ext showed markedly lower values (13 ± 4%). Based on these results, NLC-PIP-CBD iso was evaluated in a mouse pharmacokinetic study against NLC-CBD iso and CBD in hemp seed oil. While NLC-CBD iso did not improve absorption, NLC-PIP-CBD iso doubled the CBD systemic exposure, confirming that PIP codelivery significantly enhanced oral CBD absorption.