Local and Controlled Delivery of Triamcinolone for the Prevention of Fibrosis around Silicone Implants

Abstract

I propose silicone implants capable of the local, controlled release of a glucocorticoid drug, triamcinolone acetonide (TA), for the prevention of fibrosis. The shells of these silicone implants were coated with two different loading amounts of TA, which could release the drug in a sustained manner for 12 weeks. The drug-loaded implants were inserted into the subcutaneous space in living rats, and the tissues were biopsied at scheduled times during 12 weeks. For the drug-coated implants, the capsule thickness and collagen density decreased compared with those of the non-coated implant. Because of the effect of TA, inflammation and the expression of pro-inflammatory cytokines, such as TNF-α and IL-1β, were downregulated, thereby decreasing the number of monocytes during acute inflammation. This effect in turn decreased the number of macrophages at the later stage of inflammation, leading to the expression of less TGF-β and consequently fewer fibroblasts and myofibroblasts. Notably, with an appropriate dose of TA, skin and muscle atrophy, major side effects of TA, could be avoided while still effectively reducing fibrosis. Therefore, I conclude that the local, sustained release of an appropriate dose of a glucocorticoid drug can be a promising strategy for safely preventing fibrosis around silicone implants.