Advanced Healthcare Materials
·
2023
·Vol. 12
·期 26
·2300848
·
IF 10
Hairong Wang,Yi Xie,Yanling Chen,He Zhao,Xinjing Lv,Zimu Zhang,Gen Li,Jian Pan,Jian Wang,Zhuang Liu
Pathogenic bacteria induce subcutaneous infections pose serious threats to global public health. Recently, photodynamic therapy (PDT) has been proposed as a non-invasive approach for anti-microbial treatment without the risk to induce drug resistance. However, due to the hypoxic environment of most anaerobiont-infected sites, the therapeutic efficacy of oxygen consuming PDT has been limited. Herein, a transdermal delivery system is reported to allow effective delivery of photosensitizers into infected skin for PDT treatment of skin infections by bacteria. Considering the overproduction of hydrogen peroxide (H 2 O 2 ) in the abscess area, catalase (CAT), an enzyme that triggers H 2 O 2 decomposition to generate O 2 , is conjugated with chlorine e6 (Ce6) to form a photosensitizer conjugate (Ce6-CAT) as an enhanced PDT agent against Staphylococcus Aureus . After screening a series of fluorinated low molecular weight polyethylenimine (F-PEI) with different fluorination degrees, the optimized F-PEI formulation is identified with the best transdermal delivery ability system. Upon mixing, the formed Ce6-CAT@F-PEI nanocomplex shows effective transdermal penetration after being applied to the skin surface. With light exposure of the infected skin, highly effective in vivo anti-bacterial PDT therapeutic effect with Ce6-CAT@F-PEI is observed. This work proposes a transdermal PDT therapeutic nanomedicine particularly promising for the anti-bacterial treatment of skin infections.
研究领域:
医学
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药学
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生物材料学
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产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2022
·Vol. 27
·期 14
·4613
·
IF 4.927
Haohua Liu,Yue Cai,Yuteng Chu,Xiaojie Yu,Fuhang Song,Hong Wang,Huawei Zhang,Xuanrong Sun
Chrysomycin A, a compound derived from marine microorganisms, proved to have a specific great in vitro inhibitory effect on methicillin-resistantStaphylococcus aureus(MRSA). It exhibits high safety for the skin, as well as a better therapeutic effect than the current clinical drug, vancomycin. Nevertheless, its poor water solubility highly limits the application and reduces the bioavailability. In view of this, we developed a cream of chrysomycin A (CA) to enhance the solubility for the treatment of skin infection, while avoiding the possible toxicity caused by systemic administration. A comprehensive orthogonal evaluation system composed of appearance, spreading ability, and stability was established to find the optimal formula under experimental conditions. The final product was odorless and easy to be spread, with a lustrous, smooth surface. The particle size of the product met Chinese Pharmacopoeia specifications and the entire cream showed long-term stability in destructive tests. The in vitro and in vivo studies indicated that CA cream had a similar anti-MRSA activity to commercially available mupirocin, showing its potential as an efficacious topical delivery system for skin infections treatment.Keywords:MRSA;chrysomycin A;cream;topical administration;skin infections
研究领域:
微生物学
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药剂学
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医学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
·
2020
·
IF 4.845
Shuang Zhang,Wenting Song,Hangyi Wu,Jiao Wang,Yuling Wang,Zhenhai Zhang,Huixia Lv
Fungal infections are one of the major skin healthcare issues and cause significant morbidity. Ketoconazole (KC) as a broad-spectrum antifungal drug is widely used to treat skin fungal diseases. However, its therapeutic effects are limited by low concentration, short duration of drug efficacy in the skin and severe systemic toxicity. Here, the ketoconazole loaded Lecithins-Zein nanoparticles (KLZ-NPs) with core-shell structure were designed to resolve above problems. In vitro penetration test confirmed that the ketoconazole concentration of the KLZ-NPs group in the stratum corneum and deeper layers increased significantly (2.98-fold, 1.51-fold higher to free ketoconazole, respectively). Meanwhile, follicular closing technique showed the formed nanoparticles via follicle pathway into the skin had been significantly enhanced, and the results of the visual fluorescent images also confirmed it. Additionally, in the in vivo imaging experiment, the fluorescence intensity of the single applying of the DiR-LZ-NPs was higher than that of the thrice usage of the free DiR. More importantly, the results also indicated that the accumulation of nanoparticles in the liver and spleen was significantly reduced. Hence, Lecithins-Zein nanoparticles are a promising strategy to enhance the drug concentration, prolong efficacy and reduce systemic toxicity in the topical administration for antifungal treatment.
研究领域:
药学
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纳米技术
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皮肤病学
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产品关联
DOI
PubMed
高影响因子
Biomaterials Science
·
2023
·
IF 6.6
Gao-Feng Qi,Xin Cui,Xue-Feng Gong,Xu Cui,Huan-Ge Xu,Qi-Lin Liang,Kuo Zhang,Xiao-Ling Sha,Litao Li,Gui-Yuan Wang,Hong-Wen Liang,Lei Wang
Fungal infections contribute substantially to human morbidity and mortality. Particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows the morphological transformation of biphasic fungi, inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broadspectrum antifungal fluconazole, AFP achieved the comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibits the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy than fluconazole. In systemic candidiasis mice model, AFP showed similar efficacy with first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for the anti-fungal infection.
研究领域:
药学
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微生物学
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生物技术
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产品关联
DOI
PubMed
高影响因子
Microbiology Spectrum
·
2022
·
IF 9.043
Chenghua Song,Ruichao Wen,Jiaxuan Zhou,Xiaoyan Zeng,Zi Kou,Yufeng Li,Feng Yun,Rongqian Wu
Due to the changes in pathogenic species and the absence of research on topical skin antibiotics, the therapy of skin and soft tissue infections (SSTIs) is facing more and more severe challenges. It is particularly urgent to look for alternative therapies without induction of drug resistance. UV C (UVC) light within the range of 200 to 280 nm is one of the most common techniques used to kill and/or inactivate pathogenic microorganisms. However, the traditional most commonly used wavelength of 254 nm irradiated from a low-pressure mercury lamp is hazardous to human health, being both carcinogenic and damaging to eye tissues, which limits its applications in vivo. This research aimed to investigate the antimicrobial properties and influence of 275-nm UVC light from a light-emitting diode (UVC-LED light) on wound healing time. Five bacteria, three fungi, and scalded-mouse models combined with SSTIs were used to evaluate the antimicrobial effect in vitro and in vivo. 275-nm UVC-LED light inactivated both bacteria and fungi with a very short irradiation time in vitro and induced neither DNA damage nor epidermal lesions in the mice’s skin. Furthermore, in mouse models of SSTIs induced by either methicillin-resistant Staphylococcus aureus (MRSA) or Candida albicans, the 275-nm UVC-LED light showed significant antimicrobial effects and shortened the wound healing time compared with that in the no-irradiation group. UVC-LED light at 275 nm has the potential to be a new form of physical therapy for SSTIs.IMPORTANCE As a common clinical problem, the therapy of SSTIs is facing growing challenges due to an increase in the number of drug-resistant bacteria and fungi. UV C (UVC) light sterilization has been widely used in all aspects of daily life, but there are very few reports about in vivo therapy using UVC light. It is well known that prolonged exposure to UVC light increases the possibility of skin cancer. In addition, it is also very harmful for eyes. UV irradiation with 254-nm UVC light can cause corneal damage, like thinning of the corneal epithelial layer, superficial punctate keratitis, corneal erosion, etc. In this study, we focused on looking for a more accessible light source and safer UVC wavelength, and 275-nm UVC LED light was chosen. We investigated its applicability for SSTIs therapy with relative skin safety and expected that it could be used as a new physical therapy method for SSTIs.
研究领域:
微生物学
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生物医学工程
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传染病
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光疗
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伤口护理
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产品关联
DOI
PubMed
高影响因子
DRUG DELIVERY
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2022
·
IF 6.819
Ying Zhou,Chong-Yang Cai,Cheng Wang,Guo-Ming Hu,Yu-Ting Li,Meng-Jiao Han,Shen Hu,Pu Cheng
Skin infection is a major health issue that usually is caused by the continuous proliferation of bacteria in wounds. With the abuse of antibiotics worldwide, the battle against skin infection is becoming more and more difficult. Therefore, the development of new ways with different antibacterial mechanisms to current antibiotics is urgently needed. Inspired by the powerful inhibition of ferroptosis used in cancer therapy, here in our study, ferric-loaded lipid nanoparticles (Fe-LNPs) with unform size (∼130 nm) and surface charge (∼12 mV) were constructed and found to effectively inhibit the growth of both Gram positive (Staphylococcus aureus, S. aureus) and negative (Escherichia coli, E. coli) strains, possibly due to induction of ferroptosis-like cell death mechanisms. Most importantly, Fe-LNPs can also effectively inhibit the proliferation of S. aureus in a skin infection model and promote the healing of wounds. The Fe-LNPs can be applied as a powerful antibacterial formulation for future application in clinic.
研究领域:
纳米技术
·
药学
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微生物学
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伤口愈合
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2024
·
IF 13.3
Zhiyuan Zheng,Shuwei Shen,Hui Shi,Peng Yao,Zhiqiang Zhu,Chi Zhang,Siping Zhang,Xianglong Hu,Ronald X. Xu
Deep cutaneous infections pose formidable challenges for conventional topical treatments due to limited drug transdermal efficiency and inadequate antifungal properties. This paper presents a rational engineering approach to develop biodegradable and multifunctional microneedles (MNs) that can be easily tailored for the co-delivery of both hydrophilic and hydrophobic drugs, aimed at the combined treatment of cutaneous infections. Polymyxin B (PB)-loaded Polyvinyl pyrrolidone (PVP) is casted to fabricate microneedle array, then followed by an electrospray coating of curcumin (CUR)-loaded poly(lactic-co-glycolic acid) (PLGA) particles, affording the resultant PB-PVP-MN@CUR-PLGA. Rational coating of hydrophobic PLGA shell can significantly withstand humidity, wound exudate, and pus. Comprehensive moisture resistance tests verify the sustained mechanical strength of the multifunctional MNs, even after one hour of storage at 85% relative humidity, the multifunctional MNs still maintain the potency to effectively penetrate skin tissues. In vitro and in vivo explorations confirm sustained drug release and efficient antimicrobial treatment. The promising outcomes of current multifunctional MNs lay a solid foundation for clinical translation to treat deep skin-related diseases.
研究领域:
药剂学
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生物医学工程
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药物递送系统
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传染病学
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产品关联
DOI
高影响因子
Materials Today Bio
·
2023
·
IF 8.2
Ming-Chen Sun,Ying-Fang Chen,Di Liu,Xiao-Ling Xu,Yu-Chan You,Wei Lu,Yun-Juan Shi,Ming-Yang Ren,Yi-Bin Fan,Yong-Zhong Du,Xiao-Hua Tao
The widespread utilization of mupirocin to treat methicillin-resistant Staphylococcus aureus (MRSA)-caused infectious diseases has led to the emergence of mupirocin-resistant Staphylococcus aureus (MuRSA), posing a serious global medical threat. In order to counteract MuRSA, we develop a d -α-tocopherol polyethylene glycol 1000 succinate (TPGS) modified mupirocin and silver complex (TPGS/Mup-Ag) to combat MuRSA. The surfactivity of TPGS endows Mup-Ag with a homogeneous and small particle size (∼16 nm), which significantly enhances bacterial internalization. Silver ions are released from the mupirocin-Ag complex (Mup-Ag) to exert a synergistic antibacterial activity with mupirocin. Results manifest that our strategy reduces the concentration of mupirocin that induces 50% bacterial death from about 1000 μmol/mL to about 16 μmol/mL. In vitro bacterial infection model suggests that TPGS/Mup-Ag can not only eliminate both intracellular and inhibit bacterial adhesion, but also living cells are not affected. Results of in vivo experiments demonstrate that TPGS/Mup-Ag can effectively inhibit the progression of skin infection and accelerate wound healing, as well as alleviate systemic inflammation in both the subcutaneous infection model and the wound infection model. Furthermore, this study may contribute to the development of therapeutic agents for antibiotic-resistant bacteria and offer ideas for silver-based bactericides.
研究领域:
药理学
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微生物学
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传染病
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纳米技术
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药物递送系统
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产品关联
DOI
PubMed
高影响因子
BIOORGANIC & MEDICINAL CHEMISTRY
·
2023
·
IF 3.5
Yan-Yan Zhu,Zhao-Jie Wang,Meng Zhu,Zhong-Shun Zhou,Bin-Yuan Hu,Mei-Zhen Wei,Yun-Li Zhao,Zhi Dai,Xiao-Dong Luo
It’s urgent to discover new antibiotics along with the increasing emergence and dissemination of multidrug resistant (MDR) bacterial pathogens. In the present investigation, morusin exhibited rapid bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE) by targeting the phospholipid of bacterial inner membrane, increasing membrane rigidity and disrupting bacterial homeostasis together with the membrane permeability, which caused fundamental metabolic disorders. Furthermore, morusin can also accumulate ROS, suppress H 2 S production, and aggravate oxidative damage in bacteria. Importantly, morusin also inhibited the spread of wounds and reduced the bacterial burden in the mouse model of skin infection caused by MRSA. It’s a chance to meet the challenge of existing antibiotic resistance and avoid the development of bacterial resistance, given the multiple targets of morusin.
研究领域:
微生物学
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药理学
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传染病学
·
分子生物学
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
·
2024
·
IF 7.7
Rui Luo,Dongyi Xian,Feng Li,Guiling Zhou,Ling Jiang,Jieyi Wu,Liming Lin,Yuwei Zheng,Guanyu Liu,Qian Xu,Xin Pan,Chuanbin Wu,Tingting Peng,Guilan Quan,Chao Lu
The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly- l -lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 μg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa -induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.
研究领域:
药剂学
·
纳米技术
·
微生物学
·
药物递送系统
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生物医学工程
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产品关联
DOI
PubMed
高影响因子
ACS Applied Nano Materials
·
2024
·
IF 5.3
Guangyun Hu,Xiaoqing Zhou,Baohua Zhao,Yuan Peng,Qiyun Shi,Zhiqiang Yuan,Qin Shu,Wei Qian,Yizhi Peng
Infections caused by Enterococcus fascism, Staphylococcus aureus, Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species (ESKAPE) bacteria and their biofilms considerably threaten human health. Developing antibacterial agents against ESKAPE bacteria and controlling related inflammation are urgently needed. Herein, we developed a nanosystem by coating M1 macrophage membranes onto the surface of Prussian Blue@polydopamine@IR820 nanoparticles (PDIM NPs) for determining the antimicrobial activity against skin and soft tissue infection. Upon administration, PDIM NPs actively aggregated in the infected regions of subcutaneous abscesses owing to their homologous targeting properties. Under irradiation with a near-infrared (NIR) 808 nm laser, PDIM NPs exhibited outstanding antibacterial effects via synergistic photothermal and photodynamic therapy. Thereafter, the naked Prussian Blue-based nanoparticles effectively scavenged excessive reactive oxygen species and alleviated inflammation. The mouse model demonstrated the regulation of angiogenesis, collagen deposition, and attenuated hyperinflammation. Furthermore, PDIM NPs exhibited excellent biosafety in vitro and in vivo. Therefore, PDIM NPs showed remarkable infectious site-targeting properties and antimicrobial performances and facilitated the healing of cutaneous abscesses, providing strategies for treating ESKAPE bacteria and biofilm-associated diseases.
研究领域:
纳米技术
·
药学
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生物医学工程
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传染病
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材料科学
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产品关联
DOI
高影响因子
CHEMICAL ENGINEERING JOURNAL
·
2025
·
IF 13.2
Xuyan Wei,Sicong Ren,Mucong Li,Yihan Wang,Jiameng Zhang,Shaobo Zhai,Lijun Liu,Hanchi Wang,Yanmin Zhou
The treatment of complicated infected skin wounds faces many challenges. The presence of stubborn bacterial biofilms is one of the key reasons why such wounds are difficult to heal, because the bacteria in the biofilms can resist multiple antimicrobial agents and delay the healing process by inhibiting the immune response. In order to effectively manage complicated infected wounds, we are developing a hydrogel dressing (CGOD-FNP) with multiple functions. These FNP-based phenolic network hydrogels can activate the PTT effect through near-infrared light (NIR) irradiation and inhibit iron ion metabolism to achieve dual mechanism antibacterial, thereby effectively removing bacterial biofilms. In addition, in the inflammatory response stage, the hydrogel exerts an immunomodulatory function by activating the Hippo-YAP/TAZ signaling pathway, effectively regulating the immune microenvironment of the wound, and finally showing excellent adhesion, antibacterial, immunomodulatory, and tissue healing promotion in a mouse skin infection model. Therefore, CGOD-FNP will become a promising therapeutic strategy for the clinical treatment of complicated infection injuries.
研究领域:
生物材料
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伤口愈合
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抗菌治疗
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免疫调节
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组织工程
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纳米医学
✓ 已验证
产品关联
DOI
高影响因子
危险品化学品经营许可证（带存储）