Topical Capsaicin in Poly(lactic-co-glycolic)acid (PLGA) Nanoparticles Decreases Acute Itch and Heat Pain

Abstract

Background: Capsaicin, the hot pepper agent, produces burning followed by desensitiza-tion. To treat localized itch or pain with minimal burning, low capsaicin concentrations can be re-peatedly applied. We hypothesized that alternatively controlled release of capsaicin from poly(lac-tic-co-glycolic acid) (PLGA) nanoparticles desensitizes superficially terminating nociceptors, reducing burning. Methods: Capsaicin-loaded PLGA nanoparticles were prepared (single-emulsion sol-vent evaporation) and characterized (size, morphology, capsaicin loading, encapsulation efficiency, in vitro release profile). Capsaicin-PLGA nanoparticles were applied to murine skin and evaluated in healthy human participants (n = 21) for 4 days under blinded conditions, and itch and nociceptive sensations evoked by mechanical, heat stimuli and pruritogens cowhage, ß-alanine, BAM8-22 and histamine were evaluated. Results: Nanoparticles (loading: 58 µg capsaicin/mg) released in vitro 23% capsaicin within the first hour and had complete release at 72 h. In mice, 24 h post-application Capsaicin-PLGA nanoparticles penetrated the dermis and led to decreased nociceptive behavioral responses to heat and mechanical stimulation (desensitization). Application in humans produced a weak to moderate burning, dissipating after 3 h. A loss of heat pain up to 2 weeks was observed. After capsaicin nanoparticles, itch and nociceptive sensations were reduced in response to prurito-gens cowhage, ß-alanine or BAM8-22, but were normal to histamine. Conclusions: Capsaicin nano-particles could be useful in reducing pain and itch associated with pruritic diseases that are hista-mine-independent. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.