- 學位論文
Isotretinoin固態脂質奈米顆粒經皮穿透性之研究
Study of Isotretinoin-loaded Solid Lipid Nanoparticle transdermal drug delivery
摘要
13-順式維他命A酸被認為是治療痤瘡及多種皮膚疾病之有效藥物。有研究顯示此藥於全身使用（如口服）會有致畸胎的可能性，於皮膚使用會引起刺激疼痛感。13-順式維他命A酸是最常用於治療青春痘的維他命A酸衍生物之一，有研究顯示，以固態脂質奈米顆粒包埋Isotretinoin之劑型，可以減少Isotretinoin之副作用，譬如：全身性給藥所造成的致畸胎性之危險與局部給藥時造成的皮膚刺激性。本次實驗之目的為製備不同配方之Isotretinoin劑型並且評估其經皮穿透之藥物累積量與各皮層含量分析，以提供適合皮膚用之Isotretinoin之給藥劑型。 本實驗以熱均質法製備不同配方之Isotretinoin，固態脂質奈米顆粒粒徑約為50~250 nm範圍之間，且包埋率皆達90％。以Gelucire及Hydrogenated soy phosphatidylcholine（HSPC）為主要脂質配方，不同電荷性之固態脂質奈米顆粒脂質則選用Stearylamine（SA）為正電荷固態脂質奈米顆粒之脂質組成，Lecinol為負電荷固態脂質奈米顆粒之脂質組成。此外，比較各固態脂質奈米顆粒配方與市售Isotrex軟膏劑型之體外穿皮試驗之差異。體外經皮穿透試驗中，使用皮膚為大鼠腹部，實驗裝置為Franz diffusion cell。經24小時經皮穿透試驗，評估Isotretinoin於皮膚之穿透累積量及各皮層含量。 本實驗的結果顯示，Gelucire44/14是製成固態脂質奈米顆粒不錯之選擇。此種配方具有提高Isotretinoin皮層的累積量，且能提高Isotretinoin於局部皮層分布(尤其是角質層)。預期可達到較佳之治療效果。
並列摘要
Isotretinoin, a derivative of retinoic acid (13-cis-retinoic acid), has been commonly used for the treatment of severe acne and the other dermatological diseases. It has obvious adverse side effects by oral administration. It is highly irritant to skin. 13-cis-retinoic acid is one of the most common retinoids in therapeutic use. It has been researched that encapsulation of Isotretinoin in solid lipid nanoparticles may prevent the side effect of Isotretinoin such as skin irritation in topical use, and reduce the risk of teratogenicity in systemic administration. The purpose of the present study was to prepare different formulations of Isotretinoin and to evaluate their characterization and skin-penetration activity. The results may provide a suitable for optimal formulation of Isotretinoin for dermatological use. Isotretinoin was prepared by high-pressure homogenization method. The lipid compositions of Gelucire and Hydrogenated soy phosphatidylcholine（HSPC）for non-charged, with stearylamine（SA）for cationic, with lecinol for anionic solid lipid nanoparticles. The solid lipid nanoparticles formulations had average size between 50 and 250 nm. The abdomen skin from wistar was used. The experiment was performed with Franz diffusion cells. Isotretinoin accumulative amount in receptor compartment were determined at a scheduled time period up to 24 hr. The results of this study suggest that SLN formulation of isotretinoin may be superior to conventional isotretinoin gel. The gelucire44/14 SLN may be the better choice than other SLN formulations because these formulation showed higher drug retention in skin(especially in stratum corneum).