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首页> 外文期刊>Acta biomaterialia >Preparation and in vivo evaluation of cationic elastic liposomes comprising highly skin-permeable growth factors combined with hyaluronic acid for enhanced diabetic wound-healing therapy
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Preparation and in vivo evaluation of cationic elastic liposomes comprising highly skin-permeable growth factors combined with hyaluronic acid for enhanced diabetic wound-healing therapy

机译：制备和体内评价阳离子弹性脂质体，其包含高度耐肤生长因子与透明质酸联合增强糖尿病伤口愈合治疗

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摘要

To enhance the therapeutic effects of exogenous administration of growth factors (GFs) in the treatment of chronic wounds, we constructed GF combinations of highly skin-permeable epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), and platelet-derived growth factor-A (PDGF-A). We genetically conjugated a low-molecular-weight protamine (LMWP) to the N-termini of these GFs to form LMWP-EGF, LMWP-IGF-I, and LMWP-PDGF-A. Subsequently, these molecules were complexed with hyaluronic acid (HA). Combinations of native or LMWP-fused GFs significantly promoted fibroblast proliferation and the synthesis of procollagen, with a magnification of these results observed after the GFs were complexed with HA. The optimal proportions of LMWP-EGF, LMWP-IGF-I, LMWP-PDGF-A, and HA were 1, 1, 0.02, and 200, respectively. After confirming the presence of a synergistic effect, we incorporated the LMWP-fused GFs-HA complex into cationic elastic liposomes (ELs) of 107 +/- 0.757 nm in diameter and a zeta potential of 56.5 +/- 1.13 mV. The LMWP-fused GFs had significantly improved skin permeation compared with native GFs. The in vitro wound recovery rate of the LMWP-fused GFs-HA complex was 23% higher than that of cationic ELs composed of LMWP-fused GFs alone. Moreover, the cationic ELs containing the LMWP-fused GFs-HA complex significantly accelerated the wound closure rate in a diabetic mouse model and the wound size was maximally decreased by 65% and 58% compared to cationic ELs loaded with vehicle or native GFs-HA complex, respectively. Thus, topical treatment with cationic ELs loaded with the LMWP-fused GFs-HA complex synergistically enhanced the healing of chronic wounds, exerting both rapid and prolonged effects.
机译：为了增强外源给予生长因子（GFS）治疗慢性伤口的治疗效果，我们构建了高度皮肤渗透性表皮生长因子（EGF）的GF组合，胰岛素样生长因子-1（IGF-I），和血小板衍生的生长因子-A（PDGF-A）。我们将低分子量的protamine（LMWP）与这些GFS的N-末端遗传结合，形成LMWP-EGF，LMWP-IGF-I和LMWP-PDGF-A。随后，将这些分子与透明质酸（HA）络合。天然或LMWP融合GFS的组合显着促进了成纤维细胞增殖和合成的前胶原，并在GFS与HA络合后观察到这些结果的放大率。 LMWP-EGF，LMWP-IGF-I，LMWP-PDGF-A和HA的最佳比例分别为1,1,0.02和200。在确认存在协同作用后，我们将LMWP熔融GFS-HA复合物掺入直径107 +/- 0.757nm的阳离子弹性脂质体（EL）和56.5 +/- 1.13mV的Zeta电位。与天然GFS相比，LMWP融合GFS显着提高了皮肤渗透。 LMWP稠合GFS-HA复合物的体外缠绕回收率比单独由LMWP稠合GFS组成的阳离子ELS高出23％。此外，含有LMWP稠合GFS-HA复合物的阳离子ELS显着加速了糖尿病小鼠模型中的伤口闭合速率，与装载有车辆或天然GFS-HA的阳离子ELS相比，卷绕尺寸最大程度为65％和58％复杂分别。因此，用LMWP稠合GFS-HA复合的阳离子ELS的局部处理协同增强了慢性伤口的愈合，施加快速和延长的效果。

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