An Experimental Study Of Silicone Gel Sheeting Containing Methylprednisolone Aceponate And Tranilast For Manufacture And The Effect On Rabbit Hyperplastic Scars

Background and Aims:Some research developed silicone gel sheet to depress hyperplastic scar under the pressure garments. Later nonpressure treatment for hypertrophic scars simply with SGS was found the same result. Since then, a range of SGS has been developed. The world highlights a primary role for silicon gel sheeting and intralesional corticosteroids in the management of hyperplastic scar,which are the only treatments for sufficient evidence to recommendations. But the reported clinical effective rate of SGS was limited. Hence, it is imperative to improve the clinical efficacy of SGS. Triamcinolone is common intralesional hormone injected, even using standard doses of triamcinolone (40 mg/ml), still with some patients occured side effects . Moreover triamcinolone has poor effective per cutem to permeate as topical hormone. Some patients has intractable itch and hope for clinic new methods. After selected drugs ,we developed SGS containing methylprednisolone aceponate and tranilast (MT-SGS) ,studied their pharmacy and determined optimal concentrations . Then we observed its effect on rabbit hyperplastic scars in comparison with ordinary SGS.Materials and Methods We developed MT-SGS , established high performance liquid chromatogram(HPLC) and detected system stability ,precision, drug releasing in vitro ,drug layer homogenicity and permanent stability, absorbent test through HS and physical index. 20 Kunming healthy mice were randomly divided into two groups (drug group and the control group) to observe acute general toxicity. The drug group was injected leachate of MT-SGS through vena caudalis and the control group was dealted with water for injection. 10 New Zealand white rabbits were depilated in back, randomly formed three same size segregate zones(the control zone, SGS zone, MT-SGS zone) and observed primarily cutaneous stimulation. The hyperplastic scar models were established in 24 New Zealand rabbits, and were divided equally into three groups (the HS group, SGS group, and MT-SGS group) for different treatment and parallelly observed. Then TGF-β1 andα-SMA in the scar tissues were immunohistochemically analyzed and compared the difference. The hyperplastic scar models were established in 9 New Zealand rabbits, which were divided equally into three groups (the HS group, SGS group, and MT-SGS group) for different treatment and parallelly observed. Then histamine in the scar tissues were determined and compared the difference.Results1. Silicone gel sheeting containing methylprednisolone aceponate and tranilast reached physicochemical properties of Pharmacopeia.2. HPLC for MT-SGS was estabolished .Correlated system showed stable with precision and drug releasing in vitro according with require of Pharmacopeia and drugs were controlled release. The optimal concentrations of the two drugs were screened.3. No toxication and no death were found in mice acute general toxicity and the results showed negative.4. No allergy and no death were found in rabbit primarily cutaneous stimulation and the results showed negative.5. Hyperplastic scar model was stablly established in New Zealand rabbits.6. Compared therapeutic efficacy in rabbit HS model,there were significant differences in the TGF-β1 andα-SMA levels between the MT-SGS group with the other two groups and the SGS group with the HS group .7. Compared histamine levels in rabbit HS model, there were significant differences between the MT-SGS group with the other two groups and the SGS group with the HS group .Conclusion1. Silicone gel sheeting containing methylprednisolone aceponate and tranilast reached physicochemical properties of Pharmacopeia. Correlated system showed stable and the optimal concentrations of the two drugs were determined. 2. In MT-SGS, acute general toxicity and primarily cutaneous stimulation showed negative.3. MT-SGS had better therapeutic efficacy than SGS for HS in animal models .4. MT-SGS had better inhibitory effect on histamine than SGS for HS in animal models .Such results provided experimental foundation for later research of MT-SGS in clinic and supplied a new way to treat HS.