Novel molecules for intra-oral delivery of antimicrobials to prevent and treat oral infectious diseases.
Novel molecules for intra-oral delivery of antimicrobials to prevent and treat oral infectious diseases.
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用于口腔内递送抗菌剂以预防和治疗口腔传染病的新分子。
DOI：
10.1042/bj20070810
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Dentino,AndrewR
中科院分区：
文献类型：
--
作者：
Raj,PeriathambyAntony;Rajkumar,Latha;Dentino,AndrewR
新分子被设计用于高效口腔内递送抗菌药物以预防和治疗口腔感染。唾液富酪蛋白片段与牙釉质具有高亲和力，被用作载体肽。通过 N 端残基的侧链与防御素样 12 个残基肽的 C 端连接，生成两种双功能杂合分子，一种具有酯键，另一种在载体和抗菌成分之间具有酸酐键。检查它们与 HAP（羟基磷灰石）表面的亲和力。使用 13 C-NMR 光谱测定人类全唾液中抗菌剂释放的程度。分子的念珠菌活性被确定为人类唾液中载体肽的抗菌释放的函数。使用荧光技术检查混合吸附的 HAP 表面对白色念珠菌和放线菌聚集菌的抵抗力。在人红细胞、GEC（牙龈上皮细胞）和 GFC（牙龈成纤维细胞）上测试了双功能分子的细胞毒性。研究发现它们对 HAP 矿物质具有高亲和力。在人类全唾液中，观察到抗菌剂持续释放超过 40-60 小时，并且观察到与混合解离程度一致的念珠菌活性。此外，当悬浮在澄清的人类唾液中时，双功能肽结合的 HAP 表面被发现表现出抗菌活性。混合肽对人红细胞、GEC 和 GFC 没有显示出任何毒性影响。这些新型混合物可以安全地用于口腔内递送治疗剂，以治疗和预防口腔传染病。
New molecules were designed for efficient intra-oral delivery of antimicrobials to prevent and treat oral infection. The salivary statherin fragment, which has high affinity for the tooth enamel, was used as a carrier peptide. This was linked through the side chain of the N-terminal residue to the C-terminus of a defensin-like 12-residue peptide to generate two bifunctional hybrid molecules, one with an ester linkage and the other with an anhydride bond between the carrier and the antimicrobial components. They were examined for their affinity to a HAP (hydroxyapatite) surface. The extent of the antimicrobial release in human whole saliva was determined using13C-NMR spectroscopy. The candidacidal activity of the molecules was determined as a function of the antimicrobial release from the carrier peptide in human saliva. The hybrid-adsorbed HAP surface was examined againstCandida albicansandAggregatibacter actinomycetemcomitansusing the fluorescence technique. The bifunctional molecules were tested on human erythrocytes, GECs (gingival epithelial cells) and GFCs (gingival fibroblast cells) for cytotoxicity. They were found to possess high affinity for the HAP mineral. In human whole saliva, a sustained antimicrobial release over a period of more than 40–60 h, and candidacidal activity consistent with the extent of hybrid dissociation were observed. Moreover, the bifunctional peptide-bound HAP surface was found to exhibit antimicrobial activity when suspended in clarified human saliva. The hybrid peptides did not show any toxic influence on human erythrocytes, GECs and GFCs. These novel hybrids could be safely used to deliver therapeutic agents intra-orally for the treatment and prevention of oral infectious diseases.