Design and Characterization of a Therapeutic Non-phospholipid Liposomal Nanocarrier with Osteoinductive Characteristics To Promote Bone Formation.
Design and Characterization of a Therapeutic Non-phospholipid Liposomal Nanocarrier with Osteoinductive Characteristics To Promote Bone Formation.
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具有骨诱导特性的治疗性非磷脂脂质体纳米载体的设计和表征，可促进骨骼形成。
DOI：
10.1021/acsnano.7b02702
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发表时间：
2017-08-22
期刊：
影响因子：
17.1
通讯作者：
Lee M
中科院分区：
文献类型：
--
作者：
Cui ZK;Kim S;Baljon JJ;Doroudgar M;Lafleur M;Wu BM;Aghaloo T;Lee M
立体小体是近年来发展起来的一种非磷脂类脂质体，由单链两亲分子和高含量的甾醇组成。尽管与传统的磷脂脂质体相比，立体小体的稳定性显著提高，但目前的立体小体生物材料并不具有真正的生物活性，也没有内在的治疗效果。本研究的目的是通过有效地选择类固醇体组分之一的甾醇来开发具有骨诱导特性的类固醇体制剂。氧化甾醇是胆固醇的氧化衍生物，已知可以刺激成骨和骨形成。因此，20S-羟基胆固醇(Oxy)，一种最有效的骨再生氧合甾醇，被认为是与单链双亲分子硬脂胺(SA)形成流体层状相的有希望的候选分子。首先，通过研究SA/Oxy混合物的相行为，确定了SA/Oxy混合物的最佳组成。接下来，在水凝胶环境中评估优化后的SA/Oxy甾体体外促进骨髓基质细胞成骨分化的能力。此外，我们还利用小鼠临界大小的颅骨缺损模型，探讨了成骨氧合甾体在体内的作用。结果表明，SA/Oxy类固醇小体在体外诱导成骨分化，并促进颅骨愈合，而不需要额外的治疗药物，这表明其内在的成骨能力。这项研究提出了一种具有骨诱导特性的非磷脂脂质体平台，用于输送小分子药物和/或其他促进骨形成的治疗基因。
Sterosomes are a recently developed type of non-phospholipid liposomes formed from single-chain amphiphiles and high content of sterols. Although sterosomes presented significantly increased stability compared to conventional phospholipid liposomes, current sterosome biomaterials are not truly bioactive and have no intrinsic therapeutic effects. The purpose of this study was to develop a sterosome formulation with osteoinductive properties by an effective selection of sterol, one of the sterosome components. Oxysterols are oxidized derivatives of cholesterol and are known to stimulate osteogenesis and bone formation. Thus, 20S-hydroxycholesterol (Oxy), one of the most potent oxysterols for bone regeneration was examined as a promising candidate molecule to form fluid lamellar phases with a single-chain amphiphile, namely stearylamine (SA). First, the optimal composition was identified by investigating the phase behavior of SA/Oxy mixtures. Next, the capacity of the optimized SA/Oxy sterosomes to promote osteogenic differentiation of bone marrow stromal cells was assessed in vitro in a hydrogel environment. Furthermore, we explored the effects of osteogenic oxysterol sterosomes in vivo with the mouse critical-sized calvarial defect model. Our results showed that SA/Oxy sterosomes induced osteogenic differentiation in vitro and enhanced calvarial healing without delivery of additional therapeutic agents, indicating their intrinsic bone forming potential. This study suggests a promising non-phospholipid liposomal platform with osteoinductive properties for delivery of small molecular drugs and/or other therapeutic genes for enhanced bone formation.
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DOI：
10.1039/c6tb01154c
发表时间：
2016-08-21
期刊：
Journal of materials chemistry. B
影响因子：
--
作者：
Kim S;Cui ZK;Fan J;Fartash A;Aghaloo TL;Lee M
通讯作者：
Lee M
影响因子：
3.4
作者：
Cui, Zhong-Kai;Bastiat, Guillaume;Lafleur, Michel
通讯作者：
Lafleur, Michel
影响因子：
3.9
作者：
Cui, Zhong-Kai;Bouisse, Anne;Lafleur, Michel
通讯作者：
Lafleur, Michel
影响因子：
14
作者：
Hokugo, Akishige;Saito, Takashi;Jarrahy, Reza
通讯作者：
Jarrahy, Reza
影响因子：
9.7
作者：
Choi, Bogyu;Kim, Soyon;Lee, Min
通讯作者：
Lee, Min