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
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
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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DOI
PubMed
高影响因子
Microbial Cell Factories
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2022
·Vol. 21
·期 1
·1-10
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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
JOURNAL OF RARE EARTHS
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2019
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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
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