Biodegradable nanofibrous drug delivery systems: effects of metronidazole and ciprofloxacin on periodontopathogens and commensal oral bacteria.

Biodegradable nanofibrous drug delivery systems: effects of metronidazole and ciprofloxacin on periodontopathogens and commensal oral bacteria.
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DOI:
10.1007/s00784-014-1201-x
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发表时间:
2014-12
影响因子:
3.4
通讯作者:
Gregory, Richard L.
Gregory, Richard L.
中科院分区:
医学2区
文献类型:
--
作者:
Bottino, Marco C.;Arthur, Rodrigo A.;Waeiss, R. Aaron;Kamocki, Krzysztof;Gregson, Karen S.;Gregory, Richard L.

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制备含有甲硝唑(MET)或环丙沙星(CIP)的可生物降解聚对二氧环己酮(PDS II®)静电纺丝牙周药物递送系统(以下简称基质),并研究抗生素掺入对非牙周炎和牙周炎相关细菌的影响。通过静电纺丝从PDS聚合物溶液加工纤维基质。制备含抗生素的PDS溶液以获得四个不同的组:5重量% MET,25重量% MET,5重量% CIP,25重量%总督察纯PDS用作对照。采用高效液相色谱法(HPLC)评价MET和CIP释放。由干酪乳杆菌(Lactobacillus casei,Lc)和唾液链球菌(Streptococcus salivarius,Ss)形成的双菌种生物膜生长在所有电纺基质的表面上。在生物膜生长4天后,评估生物膜上细菌的生存力。此外,使用琼脂扩散测定法对牙周病原体具核梭杆菌(Fn)和伴放线菌聚集杆菌(Aa)的抗菌性能进行了评价。一个三维互连的多孔网络中观察到不同的制造矩阵。纯PDS显示出最高的纤维直径平均值(1158±402 nm),然后是5 wt.%的组,MET(1108±383 nm),25 wt.% MET(944±392 nm),5 wt.% CIP(871±309 nm)和25 wt.% CIP(765±288 nm)。HPLC表明,含有较高量(25重量%)的基团的掺入药物随时间释放更多,而那些具有较低水平(5重量%)最少的未检测到所测试的抗生素对所测试的非牙周炎相关细菌的生物膜形成的抑制作用。同时,CIP基质抑制Fn和Aa的生长。含CIP的基质导致牙周病原体的显着抑制,而不会对牙周有益细菌的生长产生负面影响。基于已证实的牙周炎相关细菌的体外抑制,需要使用相关动物模型进行未来的体内研究以确认这些药物递送系统的有效性。
To fabricate biodegradable polydioxanone (PDS II®) electrospun periodontal drug delivery systems (hereafter referred to as matrices) containing either metronidazole (MET) or ciprofloxacin (CIP) and to investigate the effects of antibiotic incorporation on both non-periodontitis and periodontitis related bacteria. Fibrous matrices were processed from PDS polymer solution by electrospinning. Antibiotic-containing PDS solutions were prepared to obtain four distinct groups: 5 wt.% MET, 25 wt.% MET, 5 wt.% CIP, 25 wt.% CIP. Pure PDS was used as a control. High performance liquid chromatography (HPLC) was done to evaluate MET and CIP release. Dual-species biofilms formed by Lactobacillus casei (Lc) and Streptococcus salivarius (Ss) were grown on the surface of all electrospun matrices. After 4 days of biofilm growth, the viability of bacteria on biofilms was assessed. Additionally, antimicrobial properties were evaluated against periodontopathogens Fusobacterium nucleatum (Fn) and Aggregatibacter actinomycetemcomitans (Aa) using agar diffusion assay. A three-dimensional interconnected porous network was observed in the different fabricated matrices. Pure PDS showed the highest fiber diameter mean (1158±402 nm) followed in a descending order by groups 5 wt.% MET (1108±383 nm), 25 wt.% MET (944±392 nm), 5 wt.% CIP (871±309 nm), and 25 wt.% CIP (765±288 nm). HPLC demonstrated that groups containing higher amounts (25 wt.%) of incorporated drugs released more over time while those with lower levels (5 wt.%) the least. No inhibitory effect of the tested antibiotics was detected on biofilm formation by the tested non-periodontitis related bacteria. Meanwhile, CIP-containing matrices inhibited growth of Fn and Aa. CIP-containing matrices led to a significant inhibition of periodontal pathogens without negatively impairing the growth of periodontal beneficial bacteria. Based on the proven in vitro inhibition of periodontitis-related bacteria, future in vivo research using relevant animal models is needed to confirm the effectiveness of these drug delivery systems.
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