Development and characterization of new enzymatic modified hybrid calcium carbonate microparticles to obtain nano-architectured surfaces for enhanced drug loading.
Development and characterization of new enzymatic modified hybrid calcium carbonate microparticles to obtain nano-architectured surfaces for enhanced drug loading.
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DOI：
10.1016/j.jcis.2014.10.007
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发表时间：
2015-02
影响因子：
9.9
通讯作者：
G. A. Islan;M. Cacicedo;V. Bosio;Guillermo R. Castro
中科院分区：
文献类型：
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作者：
G. A. Islan;M. Cacicedo;V. Bosio;Guillermo R. Castro
假设生物聚合物-CaCO3杂化微粒暴露在水解酶中可以提供新的表面可裁剪的结构。可溶性海藻酸裂解酶降解的海藻酸链暴露在微粒表面，正在产生相当大的基质变化。孔隙率和表面积体积比的变化预计会影响药物的吸收，从而影响控制释放曲线。所开发的杂化系统可能在肺部给药方面显示出有趣的性质。实验通过在生物聚合物：海藻酸盐(Alg)或Alg-高甲氧基化果胶(HMP)的存在下胶体共沉淀CaCO3，然后用海藻酸盐裂解酶(AL)处理来制备杂化微球。用扫描电子显微镜观察了其表面结构。BET等温线证实了表面积体积比的增加。并通过生物物理方法(EDAX、DSC、FTIR、X射线衍射仪)和总碳水化合物含量的测定来阐明酶的变化。模型药物为左氧氟沙星(氟喹诺酮类抗生素)，采用吸收法。考察了微球的释药特性和对铜绿假单胞菌的抗菌活性。发现经酶处理后，微球的直径为4μm，孔隙率增加。CaCO3-Alg微球表面粗糙，CaCO3-Alg-HMP微球表面呈“纳米气球”状。经AL处理的两种微球的左氧氟沙星包封率分别是未处理微球的3倍和7倍。微球显示出受控的药物释放轮廓和增强的抗菌效果。本工作展示了在开发具有潜在应用于肺部感染治疗的新载体方面的重大进展。
HypothesisBiopolymer–CaCO3hybrid microparticles exposed to hydrolytic enzymes can provide new surface tailorable architectures. Soluble Alginate Lyase hydrolyzed alginate chains exposed on microparticle surface are generating considerable matrix changes. The change of porosity and surface to volume ratio is expected to influence absorption of drugs, thereby affecting controlled release profiles. The developed hybrid system potentially shows interesting properties for lung drug administration.ExperimentalHybrid microparticles were developed by colloidal co-precipitation of CaCO3in presence of biopolymers: alginate (Alg) or Alg–High Methoxylated Pectin (HMP), followed by treatment with Alginate Lyase (AL). Surface architectures were observed by SEM. The increase in area to volume ratio was confirmed by BET isotherms. Also, enzymatic changes were elucidated by biophysical methods (EDAX, DSC, FTIR, XRD) and determination of the total carbohydrates content. Levofloxacin (a fluoroquinolone antibiotic) as model drug was incorporated by absorption. The drug release profile and the antimicrobial activity of the microparticles were tested againstPseudomonas aeruginosa.FindingsAfter enzyme treatment, microspheres showed 4 μm diameter and increased porosity. While CaCO3–Alg microspheres resulted in a rougher surface, CaCO3–Alg–HMP ones exhibited “nano-balloon” patterns on surface. Both AL-treated microparticles showed up to 3 and 7 times higher Levofloxacin encapsulation than no treated ones. Microparticles showed controlled drug release profiles and enhanced antimicrobial effect. The present work demonstrates a significant progress in the development of new carriers with potential application for lung infections treatment.