Efficacy and Safety of Intradermal Versus Subdermal Injection of Polynucleotide for Facial Improvement: A Prospective Split‐Face Study
Hyungkyu Bae, Soo‐Bin Kim, Yu‐Ran Heo, Hyoun Jun Park, Jong Seo Kim, Nark‐Kyoung Rho, Hee‐Jin KimABSTRACT
Background
Polynucleotide‐based injectables are increasingly used to improve periocular and midface skin quality, but the optimal delivery approach remains uncertain. Because intradermal and subdermal administration differ in tissue placement and short‐term procedure‐related reactions, clarifying whether subdermal delivery can achieve comparable objective improvement with better tolerability is clinically relevant.
Aims
This study aimed to compare the efficacy and safety of intradermal versus subdermal delivery of polynucleotide for facial skin improvement using a prospective split‐face clinical design.
Patients/Methods
In this prospective split‐face study, adults seeking facial wrinkle improvement received three treatment sessions at 3‐week intervals. The left cheek received intradermal injection and the right cheek received subdermal delivery. The primary endpoint was percentage improvement from baseline to Week 12 in the Antera 3D fineline index. A prespecified non‐inferiority margin of −15% (SD − ID) was evaluated using baseline‐adjusted linear mixed‐effects modeling. Secondary objective outcomes included additional Antera 3D skin‐quality indices and skin elasticity (Cutometer R2). GAIS, post‐procedure pain (VAS), injection‐site embossing, and adverse events were recorded.
Results
Forty participants received at least one treatment, and 37 contributed imaging‐based efficacy data. Both approaches improved wrinkle‐ and texture‐related parameters from baseline. Subdermal delivery met the non‐inferiority criterion for fineline improvement at Week 12 and also showed non‐inferior results at Week 9. At Week 12, the fineline index was lower on the subdermal side than on the intradermal side. Subdermal delivery was associated with lower pain scores at all sessions and no injection‐site embossing.
Conclusions
Subdermal delivery was non‐inferior to intradermal injection for objective skin‐quality outcomes and demonstrated a more favorable tolerability profile.