School of Pharmacy and State Key Laboratory of Quality Research in Chinese Medicine Macau University of Science and Technology Taipa Macao 999078 China.
Sorbonne Université CNRS, UMR 7574, Laboratoire de Chimie de la Matière Condensée de Paris Paris F-75005 France.
Adv Sci (Weinh). 2021 Feb 18;8(7):2004213. doi: 10.1002/advs.202004213. eCollection 2021 Apr.
Associating collagen with biodegradable hydrophobic polyesters constitutes a promising method for the design of medicated biomaterials. Current collagen-polyester composite hydrogels consisting of pre-formed polymeric particles encapsulated within a low concentrated collagen hydrogel suffer from poor physical properties and low drug loading. Herein, an amphiphilic composite platform associating dense collagen hydrogels and up to 50 wt% polyesters with different hydrophobicity and chain length is developed. An original method of fabrication is disclosed based on in situ nanoprecipitation of polyesters impregnated in a pre-formed 3D dense collagen network. Composites made of poly(lactic--glycolic acid) (PLGA) and poly(lactic acid) (PLA) but not polycaprolactone (PCL) exhibit improved mechanical properties compared to those of pure collagen dense hydrogels while keeping a high degree of hydration. Release kinetics of spironolactone, a lipophilic steroid used as a drug model, can be tuned over one month. No cytotoxicity of the composites is observed on fibroblasts and keratinocytes. Unlike the incorporation of pre-formed particles, the new process allows for both improved physical properties of collagen hydrogels and controlled drug delivery. The ease of fabrication, wide range of accessible compositions, and positive preliminary safety evaluations of these collagen-polyesters will favor their translation into clinics in wide areas such as drug delivery and tissue engineering.
将胶原蛋白与可生物降解的疏水性聚酯结合起来，是设计药物输送生物材料的一种很有前途的方法。目前由预形成的聚合物颗粒包封在低浓度胶原蛋白水凝胶中的胶原蛋白-聚酯复合水凝胶存在物理性能差和载药量低的问题。在此，开发了一种将致密胶原蛋白水凝胶与高达 50wt%的不同疏水性和链长的聚酯结合起来的两亲性复合平台。本文提出了一种基于在预先形成的 3D 致密胶原蛋白网络中浸渍的聚酯原位纳米沉淀的独特制造方法。与纯胶原蛋白致密水凝胶相比，由聚（乳酸-乙醇酸）（PLGA）和聚乳酸（PLA）制成的复合材料，但不是由聚己内酯（PCL）制成的复合材料，具有改善的机械性能，同时保持高水合程度。亲脂性甾体螺内酯作为药物模型的释放动力学可以调节一个月。纤维母细胞和角质细胞对复合材料没有观察到细胞毒性。与加入预形成的颗粒不同，新工艺允许同时改善胶原蛋白水凝胶的物理性能和控制药物释放。这些胶原蛋白-聚酯易于制造，可获得广泛的组成，并且初步安全性评估为阳性，这将有利于它们在药物输送和组织工程等广泛领域转化为临床应用。
