Simões Mónica G, Hugo Ayelen, Gómez-Zavaglia Andrea, Simões Pedro N, Alves Patrícia
CIEPQPF, Department of Chemical Engineering, University of Coimbra, Rua Sílvio Lima, Pólo II-Pinhal de Marrocos, 3030-790 Coimbra, Portugal.
Center for Research and Development in Food Cryotechnology (CIDCA, CCT-CONICET), La Plata 1900, Argentina.
Pharmaceutics. 2022 Mar 29;14(4):735. doi: 10.3390/pharmaceutics14040735.
Polymer-liposome complexes (PLCs) can be efficiently applied for the treatment and/or diagnosis of several types of diseases, such as cancerous, dermatological, neurological, ophthalmic and orthopedic. In this work, temperature-/pH-sensitive PLC-based systems for controlled release were developed and characterized. The selected hydrophilic polymeric setup consists of copolymers of Pluronic-poly(acrylic acid) (PLU-PAA) and Pluronic-poly(,-dimethylaminoethyl methacrylate) (PLU-PD) synthesized by atom transfer radical polymerization (ATRP). The copolymers were incorporated into liposomes formulated from soybean lecithin, with different copolymer/phospholipid ratios (2.5, 5 and 10%). PLCs were characterized by evaluating their particle size, polydispersity, surface charge, capacity of release and encapsulation efficiency. Their cytotoxic potential was assessed by determining the viability of human epithelial cells exposed to them. The results showed that the incorporation of the synthesized copolymers positively contributed to the stabilization of the liposomes. The main accomplishments of this work were the innovative synthesis of PLU-PD and PLU-PAA by ATRP, and the liposome stabilization by their incorporation. The formulated PLCs exhibited relevant characteristics, notably stimuli-responsive attributes upon slight changes in pH and/or temperature, with proven absence of cellular toxicity, which could be of interest for the treatment or diagnosis of all diseases that cause some particular pH/temperature change in the target area.
聚合物-脂质体复合物（PLCs）可有效地应用于多种疾病的治疗和/或诊断，如癌症、皮肤病、神经疾病、眼科疾病和骨科疾病。在这项工作中，开发并表征了基于温度/pH敏感的PLCs控释系统。所选的亲水性聚合物体系由通过原子转移自由基聚合（ATRP）合成的普朗尼克-聚丙烯酸（PLU-PAA）和普朗尼克-聚甲基丙烯酸-2-二甲氨基乙酯（PLU-PD）共聚物组成。将这些共聚物以不同的共聚物/磷脂比例（2.5%、5%和10%）掺入由大豆卵磷脂制备的脂质体中。通过评估PLCs的粒径、多分散性、表面电荷、释放能力和包封效率对其进行表征。通过测定暴露于其中的人上皮细胞的活力来评估其细胞毒性潜力。结果表明，合成共聚物的掺入对脂质体的稳定有积极作用。这项工作的主要成果是通过ATRP创新合成了PLU-PD和PLU-PAA，并通过掺入共聚物实现了脂质体的稳定。所制备的PLCs表现出相关特性，特别是在pH和/或温度略有变化时具有刺激响应特性，且已证明无细胞毒性，这对于治疗或诊断在靶区域引起特定pH/温度变化的所有疾病可能具有重要意义。
