Towards the controlled delivery of endocannabinoid agonists

<p dir="ltr">Currently, pain and inflammation are major health problems, and long-term use of anti-inflammatory drugs and opioids has significant health risks. Capsaicin, a TRPV1 agonist, offers a safer alternative with analgesic and anti-inflammatory effects, but its clinical use is limited by poor solubility, rapid metabolism, and sensory irritation. To address these challenges, a mesoporous silica-based nanocarrier AMS-6 was developed with 4.5 nm and 6.3 nm pores and successfully loaded them with capsaicin (22 wt% and 40 wt%) to develop a controlled drug delivery system. Physicochemical characterizations confirmed successful loading and preservation of mesostructured. In vitro release studies in HBSS (pH 7.4) showed that 22 wt% formulation released ~80% of the drug within 2 hours, followed by sustained release, making it more suitable for cell studies than the slower releasing 40 wt% formulation. In HEK-293 Flp-In T-REx cells expressing human TRPV1, higher concentrations (10–100 µg/mL) of the 22 wt% formulation produced a prolonged intracellular Ca²+ response with slower fluorescence decline compared to free capsaicin, suggesting sustained TRPV1 activation. These results highlight the effectiveness of AMS-6 nanocarriers in enabling controlled capsaicin release and suggest their potential to enhance pain management by providing sustained modulation of TRPV1 activity.</p>