JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
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2024
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IF 4.5
Qi Zong,Guozhen Wang,Zijie Zhao,Wenzhuo Li,Xiaonan Hou,Mengfei Yao,Duo Tang,Chao Sheng,Zijia Liu,Yuchen Zheng,Zhixiang Zhou,Xiaofei Zhang,Xiao Li
Hypocrellin A (HA) is an efficient photosensitizer for photodynamic therapy in recent years. In order to improve the delivery of this photosensitizer, dissolving HA microneedles were established. Firstly, dissolving microneedles were prepared from HA by a two-step solvent casting method. Then, the dissolving HA microneedle were characterized by stereomicroscope, laser confocal microscope, scanning electron microscope, differential scanning calorimeter (DSC), X-ray diffractometer (XRD) and fourier infrared spectrometer (FTIR). Finally, the transdermal cumulative penetration experiments were conducted. The results showed that the dissolving HA microneedle has a conical shape with an average height of 650 μm. The mechanical strength endure a force of 44.78 N, resulting in 0.20 N per needle. The in vitro transdermal experiment showed that the dissolving HA microneedle almost completely dissolved in 5 minutes after insertion into the mouse skin. The depth of drug penetration through the skin can reach 601.36 μm. Moreover, the dissolving HA microneedle significantly improved the cumulative transdermal penetration efficiency of the photosensitizer through the skin. Therefore, the present study successfully established a dissolving microneedle of HA, which can quickly dissolve and significantly improve the transdermal delivery efficiency of HA.
研究领域:
药剂学
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生物医学工程
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DOI
高影响因子
INTERNATIONAL JOURNAL OF PHARMACEUTICS
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2021
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IF 5.875
Xuexue Liu,Kai Zhao,Jin Cao,Xueyong Qi,Lin Wu,Song Shen
Nanoparticles have been demonstrated to be effective in targeted drug delivery to tumor due to the enhanced permeability and retention (EPR) effect. However, the inhomogeneous distribution of the nanoparticles in the tumor and the slow release of the drug make the therapeutic effect unsatisfied. Here, we present reactive oxygen species (ROS)-responsive micelles comprising poly (ethylene glycol)-poly(propylene sulfide) (PEG-PPS) for targeted delivery and in situ release of drug. Upon the irradiation of ultrasound, the loaded sonosensitizer hypocrellin (HC) will generate ROS to trigger the disassembly of the micelles and meanwhile realize sonodynamic therapy (SDT) effect of cancer. The in vivo experiment indicates that the HC loaded PEG-PPS are biocompatible and much more efficacious than an equivalent amount of free HC in inhibiting the growth of cancer.
研究领域:
药剂学
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肿瘤学
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纳米医学
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DOI
PubMed
高影响因子
RSC Advances
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2017
·Vol. 7
·期 67
·42073-42082
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IF 3.108
Ling-Yuan Guo,Shu-Zhen Yan,Qiang Li,Qiao Xu,Xi Lin,Shan-Shan Qi,Shu-Qin Yu,Shuang-Lin Chen
Hypocrellin A (HA), a perihydroxylated polycyclic quinone isolated from the fungus of Shiraia bambusicola, exhibits a wide spectrum of biological activities in pre-clinical studies. However, poor water solubility is a major clinical constraint factor of HA, leading to unpredictable bioavailability. In this study, HA-loaded poly (lactic-co-glycolic acid) (PLGA) nanoparticles (PLGA/HA NPs) were prepared by the single-emulsion solvent-evaporation technique. Characterization of PLGA/HA NPs showed that HA was successfully encapsulated on the PLGA. The drug-loading content and encapsulation efficiency (EE) were 7.0% and 57.5%, respectively. The in vitro release profile demonstrated that HA was released more slowly from nanoparticles in pH 1.5 and pH 6.8 than in pH 7.4. Furthermore, the highest solubility of PLGA/HA NPs in aqueous solution was approximately 35.67-fold that of native HA (n-HA). PLGA/HA NPs had more superior stability compared with n-HA in physiological conditions. In this paper, a sample and sensitive LC-MS/MS method was validated for the first time to quantify HA in rat plasma. The pharmacokinetic parameters and bioavailability of HA between PLGA/HA NPs and n-HA were compared after oral administration in rat. The results implied that the relative bioavailability of PLGA/HA NPs was 2.67-fold that of n-HA, and PLGA/HA NPs had a longer half-life. Therefore, these results suggested that PLGA-blend nanoparticles improved the solubility, stability and bioavailability of HA, and could become a potential and promising carrier for the oral delivery of HA.
研究领域:
药学
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纳米技术
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药物递送系统
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DOI
高影响因子
CELLULOSE
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2019
·Vol. 27
·期 2
·991-1007
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IF 3.917
Wang Tingting,Xu Lei,Shen Huiying,Cao Xiuming,Wei Qufu,Ghiladi Reza A.,Wang Qingqing
Abstract With the aim of developing self-disinfecting materials to prevent pathogen transmission from surfaces to new hosts, here we report a simple and eco-friendly way to prepare photodynamic bacterial cellulose (BC) onto which the naturally-occurring photosensitizer hypocrellin (Hc) has been covalently appended. The resultant hypocrellin-grafted BC membrane (Hc-BC) was characterized by both physical (SEM, TGA, XRD) and spectroscopic (IR, diffuse reflectance UV–visible) methods, and the photosensitizer loading was found to be 155 nmol Hc/mg membrane. Indirect cytotoxicity tests employing mouse skin fibroblast (L929) cells showed no changes in cell viability, demonstrating that the Hc-BC membrane lacked any leachable components (e.g., unreacted coupling agent or hypocrellin) that could be cytotoxic to mammalian cells. The photodynamic antibacterial activity of Hc-BC was evaluated against gram-positive S. aureus (ATCC-6538) and gram-negative E. coli strain 8099. Our results demonstrated a 99.5 + % (2.7 log units) reduction in S. aureus upon illumination (Xe lamp, 65 ± 5 mW/cm 2 , 420–780 nm; 30 min), however, no statistically significant inactivation of E. coli was observed. Potentiation with potassium iodide was found to increase the antibacterial efficacy of Hc-BC against S. aureus to 99.997% (4.8 log units) at 10 mM KI, while E. coli was inactivated by 99.1% (2 log units) at 100 mM KI, with the increase in inactivation being attributable to short-lived reactive iodide radicals that are the major biocidal agents in the potentiation of Hc-BC by KI. Taken together, our findings demonstrated that hypocrellin-grafted bacterial cellulose is a sustainable material from which potent photodynamic antibacterial materials may be derived. Graphic abstract
研究领域:
材料科学
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生物技术
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微生物学
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DOI
高影响因子
Frontiers in Pharmacology
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2017
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IF 4.4
Lin Xi,Yan Shu-Zhen,Qi Shan-Shan,Xu Qiao,Han Shuang-Shuang,Guo Ling-Yuan,Zhao Ning,Chen Shuang-Lin,Yu Shu-Qin
Photodynamic therapy (PDT) has emerged as a potent novel therapeutic modality that induces cell death through light-induced activation of photosensitizer. But some photosensitizers have characteristics of poor water-solubility and non-specific tissue distribution. These characteristics become main obstacles of PDT. In this paper, we synthesized a targeting drug delivery system (TDDS) to improve the water-solubility of photosensitizer and enhance the ability of targeted TFR positive tumor cells. TDDS is a transferrin-modified Poly(D,L-Lactide-co-glycolide (PLGA) and carboxymethyl chitosan (CMC) nanoparticle loaded with a photosensitizer hypocrellin A (HA), named TF-HA-CMC-PLGA NPs. Morphology, size distribution, Fourier transform infrared (FT-IR) spectra, encapsulation efficiency, and loading capacity of TF-HA-CMC-PLGA NPs were characterized. In vitro TF-HA-CMC-PLGA NPs presented weak dark cytotoxicity and significant photo-cytotoxicity with strong reactive oxygen species (ROS) generation and apoptotic cancer cell death. In vivo photodynamic antitumor efficacy of TF-HA-CMC-PLGA NPs was investigated with an A549 (TFR positive) tumor-bearing model in male athymic nude mice. TF-HA-CMC-PLGA NPs caused tumor delay with a remarkable tumor inhibition rate of 63% for 15 days. Extensive cell apoptosis in tumor tissue and slight side effects in normal organs were observed. The results indicated that TDDS has great potential to enhance PDT therapeutic efficacy.
研究领域:
药学
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纳米技术
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肿瘤学
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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
Microbial Cell Factories
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2022
·Vol. 21
·期 1
·1-10
·
IF 6.352
Wen Yongdi,Liao Baosheng,Yan Xiaoxiao,Wu Zhenqiang,Tian Xiaofei
Background Hypocrellin A (HA) is a perylene quinone pigment with high medicinal value that is produced by Shiraia bambusicola Henn. (S. bambusicola) and Hypocrella bambusae (Berk. & Broome) Sacc. (Ascomycetes) with great potential in clinical photodynamic therapy. Submerged cultivation of S. bambusicola is a popular technique for HA production. However, there is not much research on how temperature changes lead to differential yields of HA production.Results The temperature regulation of submerged fermentation is an efficient approach to promote HA productivity. After a 32 °C fermentation, the HA content in the mycelia S. bambusicola (GDMCC 60438) was increased by more than three- and fivefold when compared to that at 28 °C and 26 °C, respectively. RNA sequencing (RNA-seq) analysis showed that the regulation of the expression of transcription factors and genes essential for HA biosynthesis could be induced by high temperature. Among the 496 differentially expressed genes (DEGs) explicitly expressed at 32 °C, the hub genes MH01c06g0046321 and MH01c11g0073001 in the coexpression network may affect HA biosynthesis and cytoarchitecture, respectively. Moreover, five genes, i.e., MH01c01g0006641, MH01c03g0017691, MH01c04g0029531, MH01c04g0030701 and MH01c22g0111101, potentially related to HA synthesis also exhibited significantly higher expression levels. Morphological observation showed that the autolysis inside the mycelial pellets tightly composted intertwined mycelia without apparent holes.Conclusion sThe obtained results provide an effective strategy in the submerged fermentation of S. bambusicola for improved HA production and reveal an alternative regulatory network responsive to the biosynthesis metabolism of HA in response to environmental signals.
研究领域:
微生物学
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生物技术
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分子生物学
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DOI
PubMed
高影响因子
Photodiagnosis and Photodynamic Therapy
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2019
·
IF 2.589
Asif Jan,Chengcheng Liu,Hong Deng,Jiao Li,Wenpeng Ma,Xiaoyan Zeng,Yanhong Ji
Background and aim The extensive use of antifungal drugs has led to resistance from Candida albicans . The search for alternative treatment against drug-resistant C. albicans is highly desirable. Antimicrobial photodynamic therapy (aPDT) is an emerging and promising approach for treating localized and superficial C. albicans infections. The aim of this study was to investigate the photodynamic inactivation (PDI) effects of hypocrellin B (HB) on azole-sensitive and resistant C. albicans in vitro . Methods The PDI efficacies of HB on standard C. albicans strain (ATCC 10231), azole-sensitive clinical isolate of C. albicans , and azole-resistant clinical isolate of C. albicans were assessed. The uptake of HB in C. albicans cells was investigated by confocal laser scanning microscopy (CLSM). The PDI effects on cellular structure and surface characteristics were investigated by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Results HB exhibited no significant dark toxicity, but inactivated the azole-sensitive and resistant C. albicans in a light-dose and PS concentration-dependent manner. CLSM images indicated that PDI treated C. albicans cells showed stronger fluorescence compared to untreated cells. TEM images suggested that significant damage to the cell wall, membrane, and cytoplasm were induced by HB-mediated PDI. SEM analysis revealed that the surface of C. albicans cells became twisted and ruptured after PDI treatment. Conclusions Azole-sensitive and resistant C. albicans could be effectively inactivated by HB in the presence of light, and HB-mediated aPDT shows promise as an antifungal treatment for C. albicans .
研究领域:
微生物学
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药理学
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医学研究
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF RARE EARTHS
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2019
·
IF 2.846
Cansong Lu,Yanjun Ma,Jianwen Wang
Rare earth elements (REEs) have been widely applied as efficient elicitors to improve production of biologically important secondary metabolites in plants. However, their effects on microbial secondary metabolites were seldom reported. In this study, lanthanum (LaCl 3 ) was used as an elicitor in mycelium cultures of Shiraia bambusicola to stimulate the production of hypocrellin A (HA), a promising photosensitizer for anticancer photodynamic therapy. La 3+ at 1.0 g/L not only increases HA content by 2.50-fold in mycelia, but stimulates HA exudation to the medium with the highest production (225.05 mg/L) on day 6. Further analysis shows that La 3+ can induce the intracellular ROS (reactive oxygen species) accumulation with 2.33-fold higher contents of H 2 O 2 in mycelium. HA production induced by La 3+ treatment can be suppressed by ROS scavengers. Further analysis reveals that the elicitation of La 3+ on HA accumulation is mediated by ROS generation to enhance expression of HA biosynthetical genes. The expression of ATP-binding cassette transporter gene ( SbABC ) for HA exudation is also regulated partially via ROS generated by NADPH oxidase . These results indicate that the enhanced HA production by La 3+ might be mediated by ROS signaling pathway. Our results provide a basis for understanding REE elicitation on fungal metabolites and a practical biotechnological process for enhanced production of HA.
研究领域:
微生物学
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生物技术
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DOI
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
·
2026
·
IF 5.9
Muhammad Sohail,Kai Li,Ayesha Younas,Sajid Iqbal,Xiaoxiao Chen,Baozhu Yang,Gaofeng Shu,Minjiang Chen,Hong Yuan,Jiansong Ji
CS-DHB NPs enabled pH-/laser-triggered DOX and HB codelivery for spatiotemporal HCC chemo-photothermal therapy. • Under 660 nm laser (1.0 W cm⁻²), NPs exhibited rapid hyperthermia, high ¹O₂ yield, and superior photostability. • In Hepa1-6 tumor models, NPs plus laser ensured 100% survival, marked tumor regression, and no notable toxicity. Hepatocellular carcinoma (HCC) remains lethal due to systemic chemotherapy is halted by cardiotoxicity, multidrug resistance, and poor tumor penetration. To address these limitations, we developed a novel modified chondroitin sulfate/cystamine nanoparticle, termed CS-DHB NPs, that co-delivers doxorubicin (DOX) and the photosensitizer hypocrellin B (HB) and is encapsulated within a chondroitin sulfate/cystamine nanocarrier. These engineered nanoparticles (∼154 nm) demonstrated high drug-loading efficiencies (DOX: 80%; HB: 60%), exceptional serum stability (>72 h), and dual-drug release in laser- and pH-dependent environments. Upon 660 nm laser irradiation (1.0 W cm⁻²), the CS-DHB NPs produced substantial photothermal, photodynamic effects (¹O₂ quantum yield: 0.56), and excellent photostability. The prepared CS-DHB NPs were biocompatible and showed efficient in vitro cytotoxic effects via CCK-8 assays and deep penetration and inhibition of multicellular tumor spheroids (MTS). Ex vivo cellular studies revealed that the targeted delivery mechanism, clathrin-dependent endocytosis, with laser-triggered uptake, enhanced intracellular DOX accumulation twofold. In Hepa1–6 cells, CS-DHB NPs treatment induced pronounced apoptosis (∼51%). In vivo, five intravenous administrations combined with localized laser irradiation resulted in significant tumor regression, 100% survival, minimal systemic toxicity, and no histopathological damage in a Hepa1–6-bearing C57BL/6 mice model. By integrating chemotherapy, phototherapy, and targeted release within a tumor-targeted nanosystem, CS-DHB NPs offer a promising strategy to overcome chemoresistance while preserving healthy tissues, advancing an effective, and clinically translatable approach for synergistic HCC therapy.
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DOI
PubMed
高影响因子
Photodiagnosis and Photodynamic Therapy
·
2023
·
IF 3.3
Yuanyuan Liu,Zhiqiang Cao,Guo Wei
Background The incidence of cutaneous squamous cell carcinoma (cSCC) has been demonstrating yearly increases. cSCC is a highly malignant cancer and exerts a major impact on patients' health and quality of life. Thus, the development and use of novel therapies in the treatment of cSCC are urgently needed. It has been reported that LED photodynamic therapy (LED PDT) mediated by Hypocrellin B and its derivatives, a second-generation photosensitizer, can induce apoptosis in a variety of tumor cells, However, its potential pro-apoptotic effects on cSCC have yet to be investigated. Objective This study aims to investigate the pro-apoptotic effects and molecular mechanisms of HB-LED PDT in cutaneous squamous cell carcinoma A431 cells (Subsequent abbreviation A431 cells). Such information can provide an important theoretical foundation for the clinical translation of HB-LED PDT in the treatment of cSCC. Methods 1. Effects of HB on A431 cells were determined using a Cell Counting Kit-8 assay, which method can indirectly reflect the number of living cells. In this way, this assay can then provide a means to identify the optimal concentrations of HB required for the induction of apoptosis in A431 cells. 2. The effects of HB-LED PDT on the morphology of A431 cells and changes in the nuclei after Hoechst33342 staining as determined using inverted fluorescent microscopy. 3. Use of the Annexin V-FITC test kit to detect levels of apoptosis in A431 cells in response to treatment with HB. Changes in reactive oxygen species and mitochondrial membrane potential following HB-LED PDT treatment in A431 cells were determined using fluorescence activated cell sorting (FACS). 4. Real-time quantitative PCR and Western Blot were applied to assess changes in several key factors involved in apoptosis including Bax, Bcl-2, and Caspase-3, at both transcription and translation levels. With these assays, it was possible to investigate the apoptotic signaling pathway in A431 cells in response to HB-LED PDT. Results HB-LED PDT inhibited proliferation activity and promoted nuclear fragmentation within these A431 cells. HB-LED PDT inhibited mitochondrial activity, increased reactive oxygen species production, and promoted apoptosis of A431 cells. In addition, several key factors in the apoptotic signaling pathway were increased at both the transcriptional and translational levels in A431 cells in response to the HB-LED PDT, indicating that the apoptotic signaling pathway was activated by HB-LED PDT. Conclusion HB-LED PDT induces apoptosis in A431 cells through a mitochondria-mediated apoptotic pathway. Such findings serve as an important foundation for the development of new approaches in the treatment of cSCC.
研究领域:
肿瘤学
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细胞生物学
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分子生物学
·
光疗
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DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）