International Journal of Nanomedicine
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2015
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IF 4.383
Dong Dong,Xiao Wang,Huailing Wang,Xingwang Zhang,Yifei Wang,Baojian Wu
Introduction SNX-2112 is a promising anticancer agent but has poor solubility in both water and oil. In the study reported here, we aimed to develop a nanocrystal formulation for SNX-2112 and to determine the pharmacokinetic behaviors of the prepared nanocrystals.Methods Nanocrystals of SNX-2112 were prepared using the wet-media milling technique and characterized by particle size, differential scanning calorimetry, drug release, etc. Physiologically based pharmacokinetic (PBPK) modeling was undertaken to evaluate the drug’s disposition in rats following administration of drug cosolvent or nanocrystals.Results The optimized SNX-2112 nanocrystals (with poloxamer 188 as the stabilizer) were 203 nm in size with a zeta potential of −11.6 mV. In addition, the nanocrystals showed a comparable release profile to the control (drug cosolvent). Further, the rat PBPK model incorporating the parameters of particulate uptake (into the liver and spleen) and of in vivo drug release was well fitted to the experimental data following administration of the drug nanocrystals. The results reveal that the nanocrystals rapidly released drug molecules in vivo, accounting for their cosolvent-like pharmacokinetic behaviors. Due to particulate uptake, drug accumulation in the liver and spleen was significant at the initial time points (within 1 hour).Conclusion The nanocrystals should be a good choice for the systemic delivery of the poorly soluble drug SNX-2112. Also, our study contributes to an improved understanding of the in vivo fate of nanocrystals.
研究领域:
药理学
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纳米医学
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肿瘤学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
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2015
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IF 3.85
Xingwang Zhang,Tianpeng Zhang,Yanghuan Ye,Huaqing Chen,Hua Sun,Xiaotong Zhou,Zhiguo Ma,Baojian Wu
Systemic delivery of amphiphobic drugs (insoluble in both water and oil) represents a formidable challenge in drug delivery. This work aimed to engineer a functional mesoporous carbon material to efficiently load SNX-2112, an amphiphobic anticancer agent , and to evaluate its performance in tumor-targeting delivery. Hydrothermal reaction combined with high-temperature activation was used to fabricate glucose-based mesoporous carbon nanospheres (MCNs). SNX-2112-loaded MCNs stabilized by phospholipid (SN-PMCNs) were prepared by the absorption/solvent diffusion/high-pressure homogenization method. The obtained SN-PMCNs were 180 nm around in particle size, showing a high drug load (42.7%) and acceptable physical stability. SN-PMCNs demonstrated an enhanced in vitro antitumor effect and increased uptake into cancer cells in comparison with the formulation of SNX-2112 solution (SN-Sol). The in vivo antitumor effect and biodistribution in 4T1 xenograft tumor mice, a breast cancer model, were also significantly improved through SN-PMCNs. It was shown that specific clathrin-dependent and nonspecific caveolae-dependent endocytosis were involved in the cellular trafficking of SN-PMCNs. Glucose transporter-mediated transport, prolonged body residence time and improved biodistribution via EPR effect were the main mechanisms of enhanced antitumor effect. SN-PMCNs have presented excellent tumor targeting properties and should be a promising carrier to address the systemic delivery of SNX-2112.
研究领域:
药学
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肿瘤学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2018
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IF 5.158
Xuan Liu,Xiaozhen Cheng,Fengzhe Wang,Longbao Feng,Yu Wang,Yanfang Zheng,Rui Guo
Graphene oxide (GO) is a promising material for biomedical applications, particularly in drug delivery, due to its exceptional chemical and physical properties. In this work, an innovative GO-based carrier was developed by modifying GO with chitosan (CHI) to improve the biocompatibility, and followed by the conjugation of hyaluronic acid (HA), the target ligand for CD44, to realize the specific recognition of tumor cells and improve the efficiency of anti-tumor drug delivery. The resulting product GO-CHI-HA was loaded with an anti-cancer drug SNX-2112, which is the Hsp90 inhibitor. The total release amount and release rate of SNX-2112 were significantly higher in acidic condition than in physiological condition. GO-CHI-HA with a low concentration had little impact on the lysis of red blood cells (RBCs) and blood coagulation and showed low toxicity in A549 cells and NHBE cells. The GO-CHI-HA/SNX-2112 proved to be effective in inhibiting and killing A549 cells while having lower cytotoxicity against normal human bronchial epithelial cells (NHBE cells). Furthermore, in vivo toxicity of the materials towards vital organs in SD rats were also studied through histological examinations and blood property analyses, the results of which showed that although inflammatory response was developed in the short-term, GO-CHI-HA/SNX-2112 caused no severe long-term injury. Therefore, this drug delivery system showed great potential as an effective and safe drug delivery system with little adverse side effects for cancer therapy.
研究领域:
药学
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纳米技术
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癌症研究
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
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2020
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IF 8.758
Xiangyu Deng,Wei Guan,Xiangcheng Qing,Wenbo Yang,Yimei Que,Lei Tan,Hang Liang,Zhicai Zhang,Baichuan Wang,Xiangmei Liu,Yanli Zhao,Zengwu Shao
Conventional therapeutic approaches to treat malignant tumors such as surgery, chemotherapy, or radiotherapy often lead to poor therapeutic results, great pain, economic burden, and risk of recurrence and may even increase the difficulty in treating the patient. Long-term drug administration and systemic drug delivery for cancer chemotherapy would be accompanied by drug resistance or unpredictable side effects. Thus, the use of photothermal therapy, a relatively rapid tumor elimination technique that regulates autophagy and exerts an antitumor effect, represents a novel solution to these problems. Heat shock protein 90 (HSP90), a protein that reduces photothermal or hypothermic efficacy, is closely related to AKT (protein kinase B) and autophagy. Therefore, it was hypothesized that autophagy could be controlled to eliminate tumors by combining exogenous light with a selective HSP90 inhibitor, for example, SNX-2112. In this study, an efficient tumor-killing strategy using graphene oxide loaded with SNX-2112 and folic acid for ultrafast low-temperature photothermal therapy (LTPTT) is reported. A unique mechanism that achieves remarkable therapeutic performance was discovered, where overactivated autophagy induced by ultrafast LTPTT led to direct apoptosis of tumors and enabled functional recovery of T cells to promote natural immunity for actively participating in the attack against tumors. This LTPTT approach resulted in residual tumor cells being rendered in an “injured” state, opening up the possibility of concurrent antitumor and antirecurrence treatment.
研究领域:
肿瘤学
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治疗学
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免疫学
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生物医学工程
✓ 已验证
DOI
PubMed
高影响因子
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