Natural porous biosilica loaded with mupirocin for treatment of infectious wounds

doi:10.12307/2026.107

Abstract

Abstract: BACKGROUND: Synthetic mesoporous silica can be used as a drug delivery carrier for wound treatment, but the synthesis process of this carrier is relatively complex and requires the use of toxic chemicals.

OBJECTIVE: To extract natural porous silica from diatoms to achieve efficient loading of the antibiotic mupirocin for the treatment of infected wounds.

METHODS: (1) Diatom frustules (natural porous silica) were extracted from Nitzschia, Stratus algae and Amphiprion by high-temperature sintering. The morphology, size, pore structure and biocompatibility of the three diatom frustules were characterized. Synthetic mesoporous silica and the three diatom frustules were immersed in mupirocin solution to prepare drug delivery systems, and the drug loading, encapsulation efficiency and in vitro drug release behavior were tested. According to the drug loading and encapsulation efficiency, suitable diatom frustules were selected for subsequent experiments. The inhibitory effect of Stratus algae frustules on Staphylococcus aureus and Escherichia coli was detected by the supernatant containing mupirocin collected in the inhibition zone experiment and in vitro drug release behavior. (2) Twelve SD rats were selected, and two round full-thickness skin wounds with a diameter of 1.0 cm were made on the back of each rat, and Staphylococcus aureus suspension was dripped onto the wound. After 24 hours of bacterial liquid dripping, the rats were randomly divided into four intervention groups: the blank group (n=3) had no intervention on the wound; the mupirocin group (n=3) had mupirocin solution dripped onto the wound; the straight-chain algae frustule group (n=3) had straight-chain diatom frustule solution dripped onto the wound, and the drug-loaded straight-chain algae frustule group (n=3) had straight-chain diatom frustule solution loaded with mupirocin dripped onto the wound, and the wound healing was observed. At 6 and 24 hours after intervention, the antibacterial effect was detected by agar plate coating experiment. On day 9 after intervention, the wound edge tissue was histologically observed by hematoxylin-eosin staining and Masson staining.

RESULTS AND CONCLUSION: (1) Different diatom frustules had different shell structures, showing the exquisite micro-nanostructure of natural diatom frustules. Nitzschia, Stratus, and Bryophyta frustules at concentrations of ≤25 μg/mL had no significant cytotoxicity to human umbilical vein endothelial cells and L929 cells. They showed drug loading efficiency comparable to or even better than that of synthetic mesoporous silica. The drug loading and encapsulation efficiency of Stratus frustules were higher than those of Nitzschia and Bryophyta frustules, and they could be used for subsequent drug loading. All four materials had good in vitro drug release properties, among which mupirocin had a higher cumulative release amount and release rate in Stratus frustules. Drug-loaded Stratus frustules could significantly inhibit the growth and reproduction of Staphylococcus aureus and Escherichia coli, and still showed strong antibacterial activity after one week of in vitro drug release. (2) At 24 hours after intervention, the number of colonies on the wound surface of the drug-loaded diatom frustule group was less than that of the other three groups (P < 0.05). Compared with the straight algae shells and mupirocin, the drug-loaded diatom shells accelerated the wound healing speed, and the wound healing rate exceeded 95% on day 9 after intervention. Hematoxylin-eosin staining and Masson staining showed that compared with the blank group and the straight algae shell group, the mupirocin group and the drug-loaded straight algae shell group had less inflammatory cell infiltration, shorter wound length, and more collagen deposition. The results show that diatom shells loaded with mupirocin can significantly accelerate wound healing.

Key words: infected wound, porous silica, Staphylococcus aureus, diatom shells, mupirocin, efficient loading, sustained release

CLC Number:

Zhang Chunlong, Peng Baowei, Chang Jiang, Yang Chen, Xu Yuhong. Natural porous biosilica loaded with mupirocin for treatment of infectious wounds[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(14): 3663-3674.

Figures/Tables 10

2.3 硅藻壳体外药物装载与释放研究结果合成介孔二氧化硅与硅藻壳负载莫匹罗星的载药量及包封率，如图5A，B所示。合成介孔二氧化硅的载药量和包封率分别为(19±5)%和(65±5)%；菱形藻壳、直链藻壳、双眉藻壳的载药量分别为(19±5)%，(25±5)%，(22±5)%，包封率分别为(56±5)%，(65±5)%，(60±5)%。相比之下，直链藻壳有着更高的载药量和包封率，因此选择直链藻壳作为后续实验的药物载体。合成介孔二氧化硅与硅藻壳负载莫匹罗星的药物累计释放量及释放率，见图5C，D。在最初的12 h内，药物突释，累计释放量为0.89-1.27 mg，累计释放率为20%-25%；在12 h之后至第7天，进入缓慢释放阶段，累计释放量为1.80-2.48 mg，累计释放率达到45%-50%。累计7 d的释放行为显示，相较于其他组分，莫匹罗星在直链藻壳中有着更高的累计释放量及释放率。直链藻壳的吸附脱附溶解曲线见图6A，孔径体积见图6B。直链藻壳的BET表面积为1.986 5 m2/g，微孔体积为0.000 818 cm3/g，微孔面积为0.997 8 m2/g，平均孔径2.546 8 nm。热重分析显示，在高温加热到800 ℃的过程中，直链藻壳整体质量下降小于0.1%，这归因于部分水汽蒸发，可忽略，载药直链藻壳整体质量损失为18.93%，见图6C，与上文中直链藻壳载药量相近，进一步验证了其高效的载药性能。红外光谱分析显示，载药直链藻壳新增的红外特征峰与单独的硅藻壳及莫匹罗星相对应，在1 095 cm?1强而宽的吸收带对应于直链藻壳的Si-O-Si反对称伸缩振动峰，在798，466 cm?1处的峰对应于直链藻壳的 Si-O键对称伸缩振动峰，在1 712 cm?1处显示特征带对应于莫匹罗星的C=O拉伸，在2 859和2 929 cm?1处对应于莫匹罗星的C-H变形，在1 150 cm?1处对应于莫匹罗星的C-O-C拉伸振动，在1 052 cm?1处对应于莫匹罗星的C-C骨架，表明药物成功载入硅藻壳中，见图6D。在去离子水介质下，莫匹罗星表现出正电性，而直链藻壳表现出较大的负电性，并且直链藻壳在吸附莫匹罗星后电负性有所增加，见图6E。由此可以推断，药物除了被介孔结构束缚之外，还通过静电吸附的方式负载于硅藻壳上。 "

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