Center for Disease Biology and Integrative Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
Department of Chemical System Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.
Colloids Surf B Biointerfaces. 2019 Jul 1;179:453-461. doi: 10.1016/j.colsurfb.2019.04.028. Epub 2019 Apr 14.
We developed a facile fabrication method for preparing poly(ethylene glycol)(PEG)-coated poly (lactic-co-glycolic acid) (PLGA) microspheres with homogeneous size distribution via a combination of mPEG-b-PLGA and Shirasu Porous Glass membrane emulsification. Subsequently, extracellular matrix (ECM) degrading enzymes, collagenase (COLase) or hyaluronidase (HAse) were loaded into the microspheres. The obtained microspheres exhibited a sustained release of COLase or HAse over 10 days. The degradation of ECM polymers by the released COLase and HAse was confirmed in vitro. Reversal of established dermal fibrosis via degradation of over-deposited ECM is a promising treatment for scleroderma. The therapeutic effects of COLase- and HAse-loaded PLGA microspheres on scleroderma were evaluated in vivo following their intradermal administration to a bleomycin-induced mice model of scleroderma. COLase- and HAse-loaded PLGA microspheres decreased scleroderma dermal thickness without altering the mechanical properties of skin, whereas the administration of free COLase and HAse solution induced overdecomposition of skin ECM and α-SMA expression. The facile one-pot synthesis of PEG-coated PLGA microspheres with high colloidal stability and narrow size distribution could be employed as a drug carrier for various diseases in future.
我们开发了一种简便的制备方法，通过 mPEG-b-PLGA 和 Shirasu 多孔玻璃膜乳化相结合，制备具有均匀粒径分布的聚乙二醇（PEG）-包覆的聚（乳酸-共-乙醇酸）（PLGA）微球。随后，将细胞外基质（ECM）降解酶，胶原酶（COLase）或透明质酸酶（HAse）载入微球中。所得微球在 10 天内持续释放 COLase 或 HAse。体外证实了释放的 COLase 和 HAse 对 ECM 聚合物的降解。通过降解过度沉积的 ECM 逆转已建立的皮肤纤维化是硬皮病的一种有前途的治疗方法。通过将 COLase 和 HAse 载入 PLGA 微球皮内给药至博来霉素诱导的硬皮病小鼠模型，评估了 COLase 和 HAse 载入 PLGA 微球对硬皮病的治疗效果。与游离 COLase 和 HAse 溶液给药相比，COLase 和 HAse 载入 PLGA 微球降低了硬皮病皮肤厚度，而不改变皮肤的机械性能，而后者诱导了皮肤 ECM 的过度分解和α-SMA 表达。具有高胶体稳定性和窄粒径分布的 PEG 包覆 PLGA 微球的简便一锅合成可在未来用作各种疾病的药物载体。
