Sustained-release of 4-hydroxytamoxifen inhibits capsular contracture after breast implant placement in a mouse model

Capsular contracture is a major complication of breast reconstruction with silicone implants, affecting patients' quality of life due to pain and esthetic concerns. Capsular contracture is considered to result from an excessive fibrous foreign body reaction to the implant, but its precise mechanism remains unclear, and no effective preventative approaches have been established. Previously, we reported that transdermal application of 4-hydroxytamoxifen (4-OH TAM), an active metabolite of TAM, inhibited capsule formation in a mouse model. Building on this, we examined whether a sustained-release system, directly delivering 4-OH TAM around the silicone implant, could achieve a similar effect with clinical applications in mind.

Fifty-one female ICR mice were divided into three groups: non-treated control (NT), 0.1 mg 4-OH TAM (0.1mg_TAM), and 1.0 mg 4-OH TAM (1.0mg_TAM). A silicone implant was inserted subcutaneously on the back of each mouse, with a silk elastin sponge impregnated with 4-OH TAM placed on top as a sustained-release system. After four weeks, capsule formation was evaluated by measuring capsule thickness, fibrillar collagen density, and chronic inflammation (CD45R).

The 1.0mg_TAM group showed a significantly reduced capsule thickness compared to the NT group (p = 0.048). Although no statistical significance was observed, a decreasing trend was noted in fibrillar collagen density and CD45R-positive cell infiltration in the 1.0mg_TAM group (p = 0.175 and p = 0.260, respectively).

We demonstrated that sustained-release administration of 4-OH TAM effectively suppresses capsule formation. Further investigations are required to explore its potential for clinical application.