Double-Blind Placebo-Controlled Randomized Study of Sporopollenin Exine (SpEC) Fragrance Encapsulation.

Objective: Sporopollenin exine capsules (SpECs) have been used to encapsulate active pharmaceutical agents for oral drug delivery. This study investigated whether fragrance encapsulated within SpECs prolonged perceived fragrance intensity compared with fragrance oil alone. Methods: A double-blind, placebo-controlled, randomized pilot study was conducted (clinical trial number: NCT07383337); ten healthy female participants (mean age 35.4 ± 5.6 years) received fragrance with SpEC-encapsulated fragrance (SpECs) on one wrist and fragrance alone (control) on the contralateral wrist. The fragrance intensity was assessed using a visual analogue scale (0-10) by both the participants and an independent blinded reviewer at baseline and after 2, 4 and 8 h. Paired Wilcoxon signed-rank tests and linear mixed-effects models were used for analysis. In vitro cytotoxicity was assessed using an ATP viability assay in human bronchial epithelial (BEAS-2B) cells exposed to SpECs or raw Lycopodium clavatum spores. Results: There were no significant differences between the formulations at baseline. From 2 h onward, SpECs was associated with significantly a higher fragrance intensity compared with the control for both participant-rated (p = 0.03 at 2 and 4 h; p = 0.005 at 8 h) and reviewer-rated assessments (p = 0.02 at 2 h; p = 0.01 at 4 h; and p = 0.008 at 8 h). Mixed-model analyses suggested a greater decline in intensity for control at 8 h for reviewer-rated assessments. In vitro, raw spores significantly reduced cell viability (as an indicator of potential allergenicity), whereas SpECs did not differ from control. Conclusions: Fragrance encapsulation within SpECs significantly prolongs measured fragrance intensity with no evidence of cytotoxicity. These findings support the potential of SpECs as a safe and effective sustained-release platform for topical fragrance formulations.