Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels.
Authors: Zscherpe Paula, Kalbitz Jutta, Weber Lisa A, Paschke Reinhard, Mäder Karsten, von Rechenberg Brigitte, Cavalleri Jessika-M V, Meißner Jessica, Klein Karina
Journal: BMC veterinary research
Summary
# Editorial Summary Equine malignant melanoma presents a significant clinical challenge in grey horses, particularly when tumours impede normal physiological functions or occupy anatomically difficult locations for surgical removal. This in vitro study investigated whether betulinic acid (BA) and its synthetic analogue NVX-207—both recognised for their anti-melanoma cytotoxicity—could penetrate equine skin at therapeutically relevant concentrations when delivered via two formulation approaches: microemulsion and microemulsion gel, with the latter tested using a novel oxygen flow-assisted (OFA) transdermal device. Using Franz-type diffusion cells over incubation periods of 5 minutes, 30 minutes, and 24 hours, researchers assessed drug permeation against the established half maximal inhibitory concentrations (IC50) for equine melanoma cells. All formulations successfully exceeded the required IC50 threshold across all timepoints; notably, NVX-207 delivered via the OFA applicator demonstrated significant time-dependent accumulation and depot effects within the skin at both 30 minutes and 24 hours (P < 0.05), suggesting superior drug retention compared to standard gel application. For practitioners considering topical melanoma management, these findings indicate that OFA-assisted delivery warrants progression to in vivo trials, potentially offering a non-invasive or minimally invasive treatment option for early-stage lesions where surgical access is problematic or aesthetically undesirable.
Read the full abstract on PubMed
Practical Takeaways
- •Both betulinic acid and NVX-207 show promise as transdermal treatments for early-stage equine melanoma, with formulations achieving therapeutic concentrations in equine skin
- •The oxygen flow-assisted applicator device may offer advantages for drug delivery by promoting deeper skin accumulation and depot formation compared to standard application methods
- •These in vitro results warrant progression to in vivo studies to validate efficacy and safety for clinical treatment of melanoma in gray horses
Key Findings
- •All tested formulations of betulinic acid (BA) and NVX-207 exceeded IC50 values for equine melanoma cells in equine skin samples regardless of incubation time
- •NVX-207 applied with oxygen flow-assisted (OFA) applicator showed significant time-dependent accumulation and depot-effect in skin after 30 min and 24 h (P < 0.05)
- •Microemulsion gels and microemulsions both demonstrated potent permeation potential into equine skin in Franz-type diffusion cell experiments