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Biocompatibility and biodistribution of dual-ligand chitosan nanocarrier modified with glycyrrhetinic acid and galatose in vivo
ChinaNanomedicine Abstracts / Nanomedicine: Nanotechnology, Biology, and Medicine 12 (2016) 449–575
Biocompatibility and biodistribution of dual-ligand chitosan nanocarrier modified with glycyrrhetinic acid and galatose in vivo Min Lia, Weijie Zhanga, Houxiang Chenb, Tao Wanb, Qi Chang Zhenga,⁎, a Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, bBiomedical Materials and Engineering Center of Wuhan University of Technology, Wuhan, China ⁎Corresponding author. E-mail address: [email protected] (Q.C. Zheng) Construction and development of novel liver targeted drug delivery systems is a highly desirable strategy to improve drug efficacy and reduce systematic side-effects for liver tumor. Our previous work synthesized a dual-ligand glycyrrhetinic acid and galatose modified chitosan (GCGA), which can target to hepatoma cells and enhance the cellular uptake in vitro via receptormediated endocytosis. Herein, we investigated the biocompatibility and biodistribution of the dualligand chitosan nanocarrier in vivo. Hemolysis assay demonstrated that GCGA nanoparticles (NPs) did not disrupt the morphology of red blood cells. Additionally, animal administration revealed that histological analysis of tissue showed no pathological changes and acute or chronic inflammation in the heart, lung, kidney, liver or spleen during 14 days after intravenous injection of GCGA NPs. Blood tests showed no abnormalities in liver or kidney function and blood routine. Moreover, the rats were sacrificed at 4 h or 24 h after intravenous injection and the distribution of NPs in each organ was observed under laser confocal fluorescence microscopy. The fluorescent intensity showed significantly higher accumulation in the liver than in other tissues at 4 h, indicating that glycyrrhetinic acid and galatose can improve the targeting property of NPs to liver. Figure shows that the fluorescence was enhanced in the liver at 24 h, indicating that more GCGA NPs accumulated into the liver. All results suggested that GCGA NPs is a potential drug or gene carrier for liver tumor.
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to the plain liposomes (PL) and the ratio of AUC in tumor to plasma increased 1.9-fold. However it remained long circulation characteristics in blood and did not distribute more than PL in normal tissues that indicated the stability and protection effect to CPP of PEG on liposomes in normal neutral physiological environment. The treatment for breast tumor on Balb/ C-nude mice showed that relative tumor growth ratio (T/C) was reduced significantly in comparison to PL. In addition, CPPL resulted in more cell apoptosis induced by DNA disruption than PL in TUNEL staining assay. Histological examination did not show any signs of necrosis or inflammation in normal tissues but a large area of cell dissolve in tumor. The findings of this study provide important and detailed information regarding the distribution of CPPL in vivo and accentuate their ability to demonstrate improved tumor penetration and treatment for breast tumor over PL.
http://dx.doi.org/10.1016/j.nano.2015.12.112
Biomolecular corona-shielded drug delivery based on ROS-responsive coordination assembly for enhanced therapeutic efficacy Hongzhi Qiaoab,c, Yahan Gaoc, Yang Shaoa, Qineng Pingc, Liuqing Dia,b,⁎, a Department of Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, China, bJiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China, cDepartment of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China ⁎Corresponding author. E-mail addresses: [email protected] (H. Qiaoa), [email protected] (L. Di)
http://dx.doi.org/10.1016/j.nano.2015.12.111
Biodistribution of doxorubicin-loaded cell penetrating peptide modified pH-sensitive liposomes and its treatment for breast tumor in Balb/c-nude mice Dan Sun, Yuang Ding, Guiling Wang, Ying Xie⁎, Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, China ⁎Corresponding author. E-mail address: [email protected] (Y. Xie) It is a potential strategy to increase the selectivity of cell penetrating peptide (CPP) to tumor by the regulation of PEG-Hz-DSPE on the surface of liposomes. In this work, we developed an efficient PEGylated liposomal nanocarrier (CPPL) containing CPP and pH-sensitive hydrazone bond to enhance doxorubicin (DOX) tumor-targeted delivery in vivo. The in vivo evaluation of the delivery vectors is essential for clinical translation. The biodistribution profile of DOX loaded liposomes was evaluated in Balb/Cnude mice bearing breast tumor after single intravenous injection at a dose of 5 mg DOX/kg body weight. We demonstrated that CPPL accumulated in breast tumor at significantly (P b 0.01) higher concentrations as compared
Stimuli-responsive drug delivery systems have been increasingly utilized to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we have developed a coordination supermolecule in response to reactive oxygen species (ROS) for sequential and site-specific delivery of triptolide. The supermolecule has a rigid core, comprising phenylboronic acid-derived carboxymethyl chitosan (PCC) and hydrocaffeoyl-carboxymethyl chitosan (HCC), crosslinked through coordination bond, and an electrostatic protein corona obtained from in-situ mice plasma, which is able to facilitate long retention in biological fluids. We demonstrate that supermolecule can stably cruise in the circulation and selectively release the intercalating triptolide via arylboronic ester switch once entering into ROSrich regions. The ROS-triggered supermolecule (ROS-triggered SM) shows a 3.8-fold increase in the cytotoxicity against MCF-7 cells compared with that of non-ROS-triggered supermolecule (ROS-triggered SM). Furthermore, a marked inhibition of tumor growth is observed in the xenograft MCF-7 tumor-bearing nude mice followed by intravenous injection of ROSresponsive coordination supermolecule. This ROS-triggered drug release system will open an avenue for the exploration of more sophisticated drug delivery system, which can differentiate ROS level to promote a superior anticancer effect.
The authors acknowledge financial support from A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
Biocompatibility and biodistribution of dual-ligand chitosan nanocarrier modified with glycyrrhetinic acid and galatose in vivo Min Lia, Weijie Zhanga, Houxiang Chenb, Tao Wanb, Qi Chang Zhenga,⁎, a Department of Hepatobiliary Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China, bBiomedical Materials and Engineering Center of Wuhan University of Technology, Wuhan, China ⁎Corresponding author. E-mail address: [email protected] (Q.C. Zheng) Construction and development of novel liver targeted drug delivery systems is a highly desirable strategy to improve drug efficacy and reduce systematic side-effects for liver tumor. Our previous work synthesized a dual-ligand glycyrrhetinic acid and galatose modified chitosan (GCGA), which can target to hepatoma cells and enhance the cellular uptake in vitro via receptormediated endocytosis. Herein, we investigated the biocompatibility and biodistribution of the dualligand chitosan nanocarrier in vivo. Hemolysis assay demonstrated that GCGA nanoparticles (NPs) did not disrupt the morphology of red blood cells. Additionally, animal administration revealed that histological analysis of tissue showed no pathological changes and acute or chronic inflammation in the heart, lung, kidney, liver or spleen during 14 days after intravenous injection of GCGA NPs. Blood tests showed no abnormalities in liver or kidney function and blood routine. Moreover, the rats were sacrificed at 4 h or 24 h after intravenous injection and the distribution of NPs in each organ was observed under laser confocal fluorescence microscopy. The fluorescent intensity showed significantly higher accumulation in the liver than in other tissues at 4 h, indicating that glycyrrhetinic acid and galatose can improve the targeting property of NPs to liver. Figure shows that the fluorescence was enhanced in the liver at 24 h, indicating that more GCGA NPs accumulated into the liver. All results suggested that GCGA NPs is a potential drug or gene carrier for liver tumor.
485
to the plain liposomes (PL) and the ratio of AUC in tumor to plasma increased 1.9-fold. However it remained long circulation characteristics in blood and did not distribute more than PL in normal tissues that indicated the stability and protection effect to CPP of PEG on liposomes in normal neutral physiological environment. The treatment for breast tumor on Balb/ C-nude mice showed that relative tumor growth ratio (T/C) was reduced significantly in comparison to PL. In addition, CPPL resulted in more cell apoptosis induced by DNA disruption than PL in TUNEL staining assay. Histological examination did not show any signs of necrosis or inflammation in normal tissues but a large area of cell dissolve in tumor. The findings of this study provide important and detailed information regarding the distribution of CPPL in vivo and accentuate their ability to demonstrate improved tumor penetration and treatment for breast tumor over PL.
http://dx.doi.org/10.1016/j.nano.2015.12.112
Biomolecular corona-shielded drug delivery based on ROS-responsive coordination assembly for enhanced therapeutic efficacy Hongzhi Qiaoab,c, Yahan Gaoc, Yang Shaoa, Qineng Pingc, Liuqing Dia,b,⁎, a Department of Pharmaceutics, Nanjing University of Chinese Medicine, Nanjing, China, bJiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, China, cDepartment of Pharmaceutics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China ⁎Corresponding author. E-mail addresses: [email protected] (H. Qiaoa), [email protected] (L. Di)
http://dx.doi.org/10.1016/j.nano.2015.12.111
Biodistribution of doxorubicin-loaded cell penetrating peptide modified pH-sensitive liposomes and its treatment for breast tumor in Balb/c-nude mice Dan Sun, Yuang Ding, Guiling Wang, Ying Xie⁎, Department of Pharmaceutics, School of Pharmaceutical Science, Peking University, Beijing, China ⁎Corresponding author. E-mail address: [email protected] (Y. Xie) It is a potential strategy to increase the selectivity of cell penetrating peptide (CPP) to tumor by the regulation of PEG-Hz-DSPE on the surface of liposomes. In this work, we developed an efficient PEGylated liposomal nanocarrier (CPPL) containing CPP and pH-sensitive hydrazone bond to enhance doxorubicin (DOX) tumor-targeted delivery in vivo. The in vivo evaluation of the delivery vectors is essential for clinical translation. The biodistribution profile of DOX loaded liposomes was evaluated in Balb/Cnude mice bearing breast tumor after single intravenous injection at a dose of 5 mg DOX/kg body weight. We demonstrated that CPPL accumulated in breast tumor at significantly (P b 0.01) higher concentrations as compared
Stimuli-responsive drug delivery systems have been increasingly utilized to promote physiological specificity and on-demand therapeutic efficacy of anticancer drugs. Here we have developed a coordination supermolecule in response to reactive oxygen species (ROS) for sequential and site-specific delivery of triptolide. The supermolecule has a rigid core, comprising phenylboronic acid-derived carboxymethyl chitosan (PCC) and hydrocaffeoyl-carboxymethyl chitosan (HCC), crosslinked through coordination bond, and an electrostatic protein corona obtained from in-situ mice plasma, which is able to facilitate long retention in biological fluids. We demonstrate that supermolecule can stably cruise in the circulation and selectively release the intercalating triptolide via arylboronic ester switch once entering into ROSrich regions. The ROS-triggered supermolecule (ROS-triggered SM) shows a 3.8-fold increase in the cytotoxicity against MCF-7 cells compared with that of non-ROS-triggered supermolecule (ROS-triggered SM). Furthermore, a marked inhibition of tumor growth is observed in the xenograft MCF-7 tumor-bearing nude mice followed by intravenous injection of ROSresponsive coordination supermolecule. This ROS-triggered drug release system will open an avenue for the exploration of more sophisticated drug delivery system, which can differentiate ROS level to promote a superior anticancer effect.
The authors acknowledge financial support from A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.