30 results on '"Gou M"'
Search Results
2. Improved antitumor activity and reduced myocardial toxicity of doxorubicin encapsulated in MPEG-PCL nanoparticles.
- Author
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Sun C, Zhou L, Gou M, Shi S, Li T, and Lang J
- Subjects
- A549 Cells, Animals, Biological Transport drug effects, Cell Line, Tumor, Cell Survival drug effects, Doxorubicin adverse effects, Female, Humans, Mice, Mice, Inbred C57BL, Micelles, Myocardium pathology, Nanoparticles, Zebrafish, Antibiotics, Antineoplastic pharmacology, Cell Proliferation drug effects, Doxorubicin pharmacology, Drug Carriers pharmacology, Heart drug effects, Neoplasms drug therapy, Polyesters pharmacology, Polyethylene Glycols pharmacology
- Abstract
Doxorubicin (Dox) is a broad-spectrum antitumor drug used for the treatment of many types of malignant tumors. Although it possesses powerful antitumor activity, its clinical application is seriously encumbered by its unselective distribution and systemic toxicities, particularly myocardial toxicity. Thus, it is imperative to modify Dox to decrease its systemic toxicities and improve its therapeutic index. In the present study, we adopted a novel type of monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles to encapsulate Dox to prepare Dox-loaded MPEG-PCL (Dox/MPEG-PCL) nanoparticles by a controllable self-assembly process. The cellular uptake efficiency and cell proliferation inhibition of the Dox/MPEG-PCL nanoparticles were examined. The antitumor activity of the Dox/MPEG-PCL nanoparticles was tested on a multiple pulmonary metastasis model of melanoma on C57BL/6 mice. Systemic toxicities and survival time were compared between the mice treated with the Dox/MPEG-PCL nanoparticles and free Dox. The potential myocardial toxicity of the Dox/MPEG-PCL nanoparticles was investigated using a prolonged observation period. Encapsulation of Dox in MPEG-PCL nanoparticles significantly improved the cellular uptake and cell proliferation inhibition of Dox in vivo. Intravenous injection of Dox/MPEG-PCL nanoparticles obtained significant inhibition of the growth and metastasis of melanoma in the lung and prolonged survival time compared with free Dox (P<0.05). The Dox/MPEG-PCL nanoparticles did not show obvious additional systemic toxicities compared with free Dox during the treatment time. During the prolonged observation period, obvious decreased cardiac toxicity was observed in the Dox/MPEG-PCL nanoparticle-treated mice compared with that observed in the free Dox-treated mice. These results indicated that encapsulating Dox with MPEG-PCL micelles could significantly promote its antitumor activity and reduce its toxicity to the myocardium.
- Published
- 2016
- Full Text
- View/download PDF
3. Efficient Inhibition of Ovarian Cancer by Gelonin Toxin Gene Delivered by Biodegradable Cationic Heparin-polyethyleneimine Nanogels.
- Author
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Bai Y, Gou M, Yi T, Yang L, Liu L, Lin X, Su D, Wei Y, and Zhao X
- Subjects
- Animals, Apoptosis genetics, Biocompatible Materials, Cations, Cell Line, Female, Gene Transfer Techniques, Heparin administration & dosage, Humans, Mice, Inbred BALB C, Mice, Nude, Nanogels, Ovarian Neoplasms pathology, Polyethylene Glycols chemistry, Polyethylene Glycols toxicity, Polyethyleneimine chemistry, Polyethyleneimine toxicity, Ribosome Inactivating Proteins, Type 1 administration & dosage, Ribosome Inactivating Proteins, Type 1 genetics, Xenograft Model Antitumor Assays, Genetic Therapy methods, Heparin chemistry, Ovarian Neoplasms therapy, Polyethylene Glycols administration & dosage, Polyethyleneimine administration & dosage, Ribosome Inactivating Proteins, Type 1 pharmacology
- Abstract
The use of toxins for cancer therapy has great promise. Gelonin, a potent plant toxin, causes cell death by inactivating the 60S ribosomal subunit. Recently, we developed a novel gene delivery system using biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels. In the current study, the antitumor activity of a recombinant plasmid expressing gelonin (pGelonin) on human ovarian cancer was assessed. The application of HPEI nanogels, was also evaluated. Gelonin-cDNA was cloned into the pVAX1 plasmid vector and transfected into SKOV3 human ovarian cancer cells using biodegradable cationic HPEI nanogels. The expression of gelonin in vitro and in vivo was confirmed using RT-PCR and western blot analysis. Cell viability and apoptosis were examined using an MTT assay and flow cytometric analysis. For the in vivo study, an SKOV3 intraperitoneal ovarian carcinomatosis model was established, and nude mice were randomly assigned into four groups receiving i.p. administration of pGelonin/HPEI complexes, pVAX/HPEI complexes, HPEI alone and 5% glucose solution. The tumor weight was monitored, and a TUNEL assay and Ki-67 immunohistochemistry were performed to evaluate apoptosis and cell proliferation in the tumor tissue sections, respectively. Gelonin was efficiently expressed in SKOV3 cancer cells in vitro and in vivo using pGelonin incorporated with HPEI nanogels. The pGelonin/HPEI complexes inhibited cell viability and induced apoptosis in the cell culture. Treatment for intraperitoneal carcinomatosis with pGelonin/HPEI complexes reduced the tumor weight by ~58.55% compared to the control groups (P<0.05). The antitumor effect was accompanied by increased apoptosis and reduced cell proliferation (P<0.05). No significant side effects were observed with i.p. administration of the pGelonin/HPEI complexes. Our data indicate that HPEI nanogel-delivered pGelonin may have promising applications against human ovarian cancer.
- Published
- 2015
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4. Antitumor effects of heparin-polyethyleneimine nanogels delivering claudin-3-targeted short hairpin RNA combined with low-dose cisplatin on ovarian cancer.
- Author
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Liu L, Gou M, Yi T, Bai Y, Wei Y, and Zhao X
- Subjects
- Animals, Apoptosis drug effects, Blotting, Western, Cell Line, Tumor, Cisplatin administration & dosage, Female, Heparin administration & dosage, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Mice, Mice, Inbred BALB C, Mice, Nude, Nanogels, RNA, Small Interfering, Transfection, Xenograft Model Antitumor Assays, Antineoplastic Agents administration & dosage, Claudin-3 antagonists & inhibitors, Genetic Therapy methods, Ovarian Neoplasms pathology, Polyethylene Glycols administration & dosage, Polyethyleneimine administration & dosage
- Abstract
Cisplatin is normally administered in chemotherapy for ovarian cancer, but is accompanied by severe dose-dependent toxicity. The combination of cisplatin with other antitumor agents may be a useful alternative for achieving higher antitumor efficiency and lower toxicity. Claudin-3 (CLDN3), a commonly upregulated gene in 90% of ovarian cancers, has been identified as a novel therapeutic target of ovarian cancer. Therefore, in the present study, we constructed a recombinant plasmid carrying an shRNA targeting CLDN3 (pshCLDN3), and investigated the antitumor effects of the combination therapy of pshCLDN3 and a low-dose of cisplatin for the treatment of ovarian cancer. Heparin-polyethyleneimine (HPEI) nanogel, a novel gene carrier with superior biodegradability, excellent blood compatibility and low-toxicity, was used to deliver pshCLDN3 into ovarian cancer cells. The knockdown efficiency was determined by western blot analysis and CLDN3 immunostaining. Nude mice bearing intraperitoneal ovarian carcinomas were treated with pshCLDN3/HPEI complexes, low-dose cisplatin, pshCLDN3/HPEI plus low-dose cisplatin or control agents, respectively. The results showed that pshCLDN3/HPEI effectively suppressed the expression of CLDN3 in ovarian cancer. The combination therapy of pshCLDN3/HPEI and low-dose cisplatin exhibited enhanced antitumor activity, when compared with either agent alone, as evidenced by mean tumor weight analysis, Ki-67 immunostaining analysis and TUNEL assay, without obvious systemic toxicity. These results indicate that pshCLDN3/HPEI combined with low-dose cisplatin demonstrates apparent synergistic antitumor activity without marked toxicity. Our study offers a novel therapeutic strategy for the treatment of ovarian cancer.
- Published
- 2014
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5. Anticancer effect and mechanism of polymer micelle-encapsulated quercetin on ovarian cancer.
- Author
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Gao X, Wang B, Wei X, Men K, Zheng F, Zhou Y, Zheng Y, Gou M, Huang M, Guo G, Huang N, Qian Z, and Wei Y
- Subjects
- Animals, Antineoplastic Agents therapeutic use, Antineoplastic Agents toxicity, Apoptosis drug effects, Caspase 3 metabolism, Caspase 9 metabolism, Cell Line, Tumor, Female, Humans, Membrane Potential, Mitochondrial drug effects, Mice, Mice, Nude, Mitogen-Activated Protein Kinases metabolism, Nanoparticles chemistry, Ovarian Neoplasms drug therapy, Ovarian Neoplasms metabolism, Ovarian Neoplasms pathology, Particle Size, Proto-Oncogene Proteins c-akt metabolism, Proto-Oncogene Proteins c-bcl-2 metabolism, Quercetin therapeutic use, Quercetin toxicity, Transplantation, Heterologous, bcl-2-Associated X Protein metabolism, Antineoplastic Agents chemistry, Micelles, Polyesters chemistry, Polyethylene Glycols chemistry, Quercetin chemistry
- Abstract
Encapsulation of hydrophobic agents in polymer micelles can improve the water solubility of cargos, contributing to develop novel drugs. Quercetin (QU) is a hydrophobic agent with potential anticancer activity. In this work, we encapsulated QU into biodegradable monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles and tried to provide proof-of-principle for treating ovarian cancer with this nano-formulation of quercetin. These QU loaded MPEG-PCL (QU/MPEG-PCL) micelles with drug loading of 6.9% had a mean particle size of 36 nm, rendering the complete dispersion of quercetin in water. QU inhibited the growth of A2780S ovarian cancer cells on a dose dependent manner in vitro. Intravenous administration of QU/MPEG-PCL micelles significantly suppressed the growth of established xenograft A2780S ovarian tumors through causing cancer cell apoptosis and inhibiting angiogenesis in vivo. Furthermore, the anticancer activity of quercetin on ovarian cancer cells was studied in vitro. Quercetin treatment induced the apoptosis of A2780S cells associated with activating caspase-3 and caspase-9. MCL-1 downregulation, Bcl-2 downregulation, Bax upregulation and mitochondrial transmembrane potential change were observed, suggesting that quercetin may induce apoptosis of A2780S cells through the mitochondrial apoptotic pathway. Otherwise, quercetin treatment decreased phosphorylated p44/42 mitogen-activated protein kinase and phosphorylated Akt, contributing to inhibition of A2780S cell proliferation. Our data suggested that QU/MPEG-PCL micelles were a novel nano-formulation of quercetin with a potential clinical application in ovarian cancer therapy.
- Published
- 2012
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6. Efficient inhibition of ovarian cancer by recombinant CXC chemokine ligand 10 delivered by novel biodegradable cationic heparin-polyethyleneimine nanogels.
- Author
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Yang F, Gou M, Deng H, Yi T, Zhong Q, Wei Y, and Zhao X
- Subjects
- Animals, Apoptosis genetics, Cell Growth Processes genetics, Cell Line, Tumor, Chemokine CXCL10 biosynthesis, Cystadenocarcinoma, Serous blood supply, Cystadenocarcinoma, Serous genetics, Cystadenocarcinoma, Serous pathology, Female, Heparin administration & dosage, Heparin chemistry, Human Umbilical Vein Endothelial Cells cytology, Humans, In Situ Nick-End Labeling, Mice, Mice, Inbred BALB C, Mice, Nude, Nanogels, Neovascularization, Pathologic genetics, Neovascularization, Pathologic pathology, Neovascularization, Pathologic therapy, Ovarian Neoplasms blood supply, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Plasmids administration & dosage, Plasmids genetics, Polyethylene Glycols chemistry, Polyethyleneimine chemistry, Transfection methods, Xenograft Model Antitumor Assays, Chemokine CXCL10 genetics, Cystadenocarcinoma, Serous therapy, Genetic Therapy methods, Ovarian Neoplasms therapy, Polyethylene Glycols administration & dosage, Polyethyleneimine administration & dosage
- Abstract
Currently, great interest is focused on the anti-neoplastic effects of CXC chemokine ligand 10 (IP-10/CXCL10). IP-10 has shown significant antitumor and anti-metastatic properties via immunological, antiangiogenic and anti-neoplastic mechanisms. However, very few studies on the antitumor activity of IP-10 in human ovarian cancer have been reported. The use of polymeric nanoparticles to deliver functional genes intraperitoneally holds much promise as an effective therapy for ovarian cancer. In our study, a recombinant plasmid expressing IP-10 (pVITRO-IP-10) was constructed, and biodegradable cationic heparin-polyethyleneimine (HPEI) nanogels were prepared to deliver pVITRO-IP-10 into SKOV3 human ovarian cancer cells. Transfection efficiency was detected by expression profiling of green fluorescent protein. The expression of IP-10 was determined using RT-PCR and western blot analysis. In vitro, cell proliferation was evaluated by MTT assay. Apoptosis was examined by Hoechst33258/PI staining and flow cytometry assays. The effect on the inhibition of angiogenesis was evaluated by tube formation assay using human umbilical vein endothelial cells (HUVECs). Moreover, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the antitumor activity of HPEI+pVITRO-IP-10 complexes in nude mice. Tumor weights were evaluated during the treatment course. Cell proliferation and apoptosis were evaluated by Ki-67 immunochemical staining and TUNEL assay, and the antiangiogenic effect of pVITRO-IP-10 was assessed by CD31 immunochemical staining and alginate-encapsulated tumor cell assay. pVITRO-IP-10 was efficiently transfected into SKOV3 cells by HPEI nanogels. Intraperitoneal administration of HPEI+pVITRO-IP-10 complexes led to effective growth inhibition of ovarian cancer, in which tumor weight decreased by ~69.92% in the treatment group compared with that in the empty vector control group. Meanwhile, decreased cell proliferation, increased tumor cell apoptosis and reduction in angiogenesis were observed in the HPEI+pVITRO-IP-10 group compared with those in the control groups. These results indicated that HPEI nanogel delivery of pVITRO-IP-10 may be of value in the treatment against human ovarian cancer.
- Published
- 2012
- Full Text
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7. Pharmacokinetics and disposition of nanomedicine using biodegradable PEG/PCL polymers as drug carriers.
- Author
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Wang Y, Gou M, Gong C, Wang C, Qian Z, Lin YF, and Luo F
- Subjects
- Animals, Delayed-Action Preparations, Drug Carriers toxicity, Humans, Micelles, Nanomedicine, Polyesters toxicity, Polyethylene Glycols toxicity, Drug Carriers pharmacokinetics, Polyesters pharmacokinetics, Polyethylene Glycols pharmacokinetics
- Abstract
Micelles assembled from amphiphilic poly(ethylene glycol)/poly(-caprolactone) (PEG/PCL) copolymers are promised as safe and effective drug delivery systems. They offer the potential to achieve high solubility of hydrophobic drugs, long blood circulation time and effective delivery to target organs. These advantages contribute to their application as vehicles of a broad variation of therapeutic compounds. In this review, we discussed the safety of the copolymers, release behavior of PEG/PCL micelles in vitro, and pharmacokinetic profiles referring to the optimized fate in vascular system and targeting biodistribution.
- Published
- 2012
- Full Text
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8. Treating colon cancer with a suicide gene delivered by self-assembled cationic MPEG-PCL micelles.
- Author
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Duan X, Wang P, Men K, Gao X, Huang M, Gou M, Chen L, Qian Z, and Wei Y
- Subjects
- Adenocarcinoma genetics, Animals, Cell Line, Tumor, Colonic Neoplasms genetics, Drug Delivery Systems, Female, Gene Transfer Techniques instrumentation, Genetic Therapy instrumentation, Genetic Vectors chemistry, Mice, Mice, Inbred BALB C, Micelles, Models, Biological, Polyesters administration & dosage, Polyethylene Glycols administration & dosage, Transfection instrumentation, Transfection methods, Adenocarcinoma therapy, Colonic Neoplasms therapy, Genes, Transgenic, Suicide genetics, Genetic Therapy methods, Polyesters therapeutic use, Polyethylene Glycols therapeutic use
- Abstract
Biodegradable cationic micelles show promise for applications in gene delivery. In this article, we used DOTAP to modify monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL, MP) micelles in one step, creating novel cationic self-assembled DOTAP and MPEG-PCL hybrid micelles (DMP). These micelles had a mean particle size of 46 ± 5.6 nm and a zeta potential of 41.8 ± 0.5 mV, and had the capacity to bind DNA. Compared with PEI25K (the gold standard), DMP micelles had higher transfection efficiency and lower cytotoxicity. Moreover, we used DMP to deliver the Survivin-T34A gene (S-T34A, a suicide gene) to treat colon cancer. DMP delivered the Survivin-T34A gene (DMP/S-T34A) and could induce apoptosis in cancer cells, resulting in inhibition of the growth of C-26 colon cancer cells in vitro. An in vivo study indicated that intraperitoneal administration of DMP micelles delivered the Survivin-T34A gene and efficiently inhibited the growth of abdominal metastatic C-26 colon cancer and the malignant ascites. These data suggest that DMP may be a novel gene carrier, and its delivery of the S-T34A gene may have promising applications in the treatment of colon cancer., (This journal is © The Royal Society of Chemistry 2012)
- Published
- 2012
- Full Text
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9. Efficient inhibition of an intraperitoneal xenograft model of human ovarian cancer by HSulf-1 gene delivered by biodegradable cationic heparin-polyethyleneimine nanogels.
- Author
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Liu P, Gou M, Yi T, Xie C, Qi X, Zhou S, Deng H, Wei Y, and Zhao X
- Subjects
- Animals, Apoptosis genetics, Body Weight, Cations chemistry, Cell Line, Tumor, Cell Proliferation, Disease Models, Animal, Female, Gene Expression, Gene Expression Regulation, Neoplastic, Genetic Therapy, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Nanogels, Neoplasm Invasiveness genetics, Neovascularization, Pathologic therapy, Ovarian Neoplasms blood supply, Ovarian Neoplasms pathology, Polyethylene Glycols toxicity, Polyethyleneimine toxicity, Sulfotransferases metabolism, Xenograft Model Antitumor Assays, Gene Transfer Techniques, Heparin chemistry, Ovarian Neoplasms therapy, Polyethylene Glycols chemistry, Polyethyleneimine chemistry, Sulfotransferases genetics
- Abstract
The HSulf-1 (heparan sulfate 6-O-endosulfatase 1) gene is an important element that modulates the sulfation status of heparan sulfate proteoglycans (HSPGs), leading to the interference of HSPG-related signal transduction pathways. HSulf-1 plays a key role in regulating cell proliferation, tumorigenesis and angiogenesis. Recently, some studies have reported that HSulf-1 is a down-regulated gene in the majority of examined tumor types. In our present study, a recombinant plasmid DNA carrying HSulf-1-cDNA (pHSulf-1) was constructed. The antitumor effect of pHSulf-1 delivered by heparin-polyethyleneimine (HPEI) nanogels on human ovarian cancer and the possible mechanisms of the antitumor efficacy in vivo were further investigated. Heparin-polyethyleneimine (HPEI) nanogels, as a new safe non-viral gene delivery carrier, were prepared to deliver the plasmid expressing HSulf-1 into HSulf-1-deficient SKOV3 human ovarian cancer cells in vitro and in vivo. pHSulf-1 could be efficiently transfected into SKOV3 ovarian cancer cells by HPEI nanogels in vitro and in vivo. Stable expression of HSulf-1 in vitro and in vivo was verified by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. Furthermore, a SKOV3 intraperitoneal ovarian carcinomatosis model was established to investigate the growth inhibition function of pHSulf-1 in nude mice. Tumor weight was measured. An anti-angiogenesis effect of pHSulf-1 in vivo was detected by CD31 immunostaining and alginate-encapsulate tumor cell assay. Assessment of apoptotic cells and proliferation index in tumor tissues were performed by TUNEL assay and Ki‑67 immunostaining. Intraperitoneal injection of pHSulf-1/HPEI complexes efficiently reduced tumor weight by approximately 87% compared with control groups (P<0.01). Meanwhile, reduction in angiogenesis, inhibition of cell proliferation, as well as induction of tumor cell apoptosis were observed, without apparent systemic toxic effects. Collectively, these observations provide the first evidence that pHSulf-1 delivered by HPEI nanogels may become a promising therapeutic strategy against human ovarian cancer.
- Published
- 2012
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10. Adenoviral vectors modified by heparin-polyethyleneimine nanogels enhance targeting to the lung and show therapeutic potential for pulmonary metastasis in vivo.
- Author
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Wei W, Mu Y, Li X, Gou M, Zhang H, Luo S, Men K, Mao Y, Qian Z, and Yang L
- Subjects
- Animals, Cell Proliferation drug effects, Drug Carriers administration & dosage, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Drug Carriers pharmacology, Female, Genetic Therapy methods, Genetic Vectors genetics, Genetic Vectors pharmacokinetics, Genetic Vectors pharmacology, HeLa Cells, Heparin chemistry, Heparin pharmacokinetics, Histocytochemistry, Humans, Lung chemistry, Lung metabolism, Lung Neoplasms metabolism, Mice, Mice, Inbred BALB C, Nanogels, Neoplasm Metastasis, Polyethylene Glycols chemistry, Polyethylene Glycols pharmacokinetics, Polyethylene Glycols pharmacology, Polyethyleneimine chemistry, Polyethyleneimine pharmacokinetics, Polyethyleneimine pharmacology, Xenograft Model Antitumor Assays, Adenoviridae genetics, Genetic Vectors administration & dosage, Heparin administration & dosage, Lung Neoplasms secondary, Lung Neoplasms therapy, Polyethylene Glycols administration & dosage, Polyethyleneimine administration & dosage, Transfection methods
- Abstract
Polyethyleneimine (PEI) is a well-known cationic polymer that has previously been shown to have significant potential to deliver genes in vitro and in vivo. However, PEI is non-degradable and exhibits a high cytotoxicity as its molecular weight increases. The clinical application for systemic administration of adenoviral (Ad) vectors is limited, as these vectors do not efficiently penetrate solid tumor masses due to a common deficiency of Coxsackie Adenovirus Receptor (CAR) on the tumor surface. In this study, we conjugated low molecular weight PEI (Mn = 1,800) to heparin (Mn = 4,000-6,000) to create a new type of cationic degradable nanogel (HPEI) that was then used to modify Ad vectors. The resulting HPEI-Ad complexes were used to infect CT26 and HeLa cells in vitro. Additionally, the HPEI-Ad complexes were administrated in vivo via intravenous injection, and tissue distribution was assessed using luciferase assays; the therapeutic potential of HPEI-Ad complexes for pulmonary metastasis mediated by CT26 cells was also investigated. In vitro, HPEI-Ad complexes enhanced the transfection efficiency in CT26 cells, reaching 36.3% compared with 0.1% of the native adenovirus. In vivo, HPEI-Ad complexes exhibited greater affinity for lung tissue than the native adenovirus and effectively inhibited the growth of pulmonary metastases mediated by CT26 cells. Our results indicate that Ad vectors modified by HPEI nanogels to form HPEI-Ad complexes enhanced transfection efficiency in CT26 cells that lacked CAR, targeted to the lung and demostrated a potential therapy for pulmonary metastasis.
- Published
- 2011
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11. Preparation of core cross-linked PCL-PEG-PCL micelles for doxorubicin delivery in vitro.
- Author
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Zhang J, Men K, Gu Y, Wang X, Gou M, Guo G, Luo F, and Qian Z
- Subjects
- Animals, Antibiotics, Antineoplastic pharmacokinetics, Cell Line, Tumor, Cell Survival, Doxorubicin pharmacokinetics, Drug Delivery Systems methods, Drug Stability, HEK293 Cells, Humans, Hydrogen-Ion Concentration, Mice, Microscopy, Electron, Transmission, Nanoparticles chemistry, Nanoparticles ultrastructure, Nuclear Magnetic Resonance, Biomolecular, Particle Size, Polyesters pharmacokinetics, Polyethylene Glycols pharmacokinetics, Spectrometry, Fluorescence, Antibiotics, Antineoplastic administration & dosage, Antibiotics, Antineoplastic chemistry, Doxorubicin administration & dosage, Doxorubicin chemistry, Micelles, Polyesters administration & dosage, Polyesters chemistry, Polyethylene Glycols administration & dosage, Polyethylene Glycols chemistry
- Abstract
Doxorubicin has been widely used in cancer treatment, but its severe side-effects restrict its clinical application greatly. So, we hope to design a novel delivery system to decrease its side-effects. In this paper, we prepared core cross-linked micelle based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (CCPCEC) at about 30 nm in diameter with a narrow distribution. The prepared core cross-linked PCL-PEG-PCL micelles were employed to load doxorubicin by pH-induced self-assembly method. Doxorubicin-loading did not obviously affect the micelle size or size distribution. Furthermore, these micelles exhibited a significantly enhanced thermodynamic stability against dilution with aqueous solvents and showed CMC in the range of 1 x 10(-3) to 2 x 10(-3) mg/mL. Cytotoxicity study confirmed great biocompatibility of the micelles and showed that the encapsulated doxorubicin in CCPCEC micelles enhanced the cytotoxicity of doxorubicin on C26 cell line in vitro. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free doxorubicin and much slower and sustained release of doxorubicin-loaded core cross-linked micelles. In addition, a faster DOX-release from micelles at pH 5.5 than that at pH 7.4 was also observed. These results suggested that this new biodegradable Core Cross-linked PCL-PEG-PCL Micelles might be potential carriers for drug delivery in cancer chemotherapy.
- Published
- 2011
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12. Preparation of anti-CD40 antibody modified magnetic PCL-PEG-PCL microspheres.
- Author
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Gao X, Kan B, Gou M, Zhang J, Guo G, Huang N, Zhao X, and Qian Z
- Subjects
- Antibodies immunology, Antibodies metabolism, CD40 Antigens immunology, CD40 Antigens metabolism, Cell Separation, Humans, Microscopy, Electron, Transmission, Microscopy, Fluorescence, Nanotechnology, Nuclear Magnetic Resonance, Biomolecular, Antibodies chemistry, CD40 Antigens chemistry, Magnetite Nanoparticles chemistry, Microspheres, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
Antibody modified magnetic polymeric microspheres have potential biomedical application. In this paper, anti-CD40 antibody modified magnetic poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) microspheres were prepared. First, PCL-PEG-PCL triblock copolymer was synthesized by ring-opening polymerization, followed by reaction with succinic anhydride, creating carboxylated PCL-PEG-PCL copolymer. Then, magnetite nanoparticles were encapsulated into carboxylated PCL-PEG-PCL microspheres, forming magnetic PCL-PEG-PCL microspheres with carboxyl group on their surface. Catalyzed by EDC/NHS, the anti-CD40 antibody was linked to these magnetic PCL-PEG-PCL microspheres, thus forming anti-CD40 modified PCL-PEG-PCL microspheres. These anti-CD40 antibody modified magnetic PCL-PEG-PCL microspheres may have potential application in cell separation.
- Published
- 2011
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13. Improving anticancer activity and reducing systemic toxicity of doxorubicin by self-assembled polymeric micelles.
- Author
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Gou M, Shi H, Guo G, Men K, Zhang J, Zheng L, Li Z, Luo F, Qian Z, Zhao X, and Wei Y
- Subjects
- Animals, Antibiotics, Antineoplastic adverse effects, Antibiotics, Antineoplastic chemistry, Antibiotics, Antineoplastic therapeutic use, Cell Line, Tumor, Doxorubicin adverse effects, Female, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Micelles, Treatment Outcome, Colonic Neoplasms drug therapy, Colonic Neoplasms pathology, Doxorubicin chemistry, Doxorubicin therapeutic use, Drug Carriers chemistry, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
In an attempt to improve anticancer activity and reduce systemic toxicity of doxorubicin (Dox), we encapsulated Dox in monomethoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) micelles by a novel self-assembly procedure without using surfactants, organic solvents or vigorous stirring. These Dox encapsulated MPEG-PCL (Dox/MPEG-PCL) micelles with drug loading of 4.2% were monodisperse and ∼ 20 nm in diameter. The Dox can be released from the Dox/MPEG-PCL micelles; the Dox-release at pH 5.5 was faster than that at pH 7.0. Encapsulation of Dox in MPEG-PCL micelles enhanced the cellular uptake and cytotoxicity of Dox on the C-26 colon carcinoma cell in vitro, and slowed the extravasation of Dox in the transgenic zebrafish model. Compared to free Dox, Dox/MPEG-PCL micelles were more effective in inhibiting tumor growth in the subcutaneous C-26 colon carcinoma and Lewis lung carcinoma models, and prolonging survival of mice bearing these tumors. Dox/MPEG-PCL micelles also induced lower systemic toxicity than free Dox. In conclusion, incorporation of Dox in MPEG-PCL micelles enhanced the anticancer activity and decreased the systemic toxicity of Dox; these Dox/MPEG-PCL micelles are an interesting formulation of Dox and may have potential clinical applications in cancer therapy.
- Published
- 2011
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14. Co-delivery honokiol and doxorubicin in MPEG-PLA nanoparticles.
- Author
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Wang B, Gou M, Zheng X, Wei X, Gong C, Wang X, Zhao Y, Luo F, Chen L, Qian Z, and Yang L
- Subjects
- Cell Line, Tumor, Humans, Polyesters, Antineoplastic Agents administration & dosage, Biphenyl Compounds administration & dosage, Doxorubicin administration & dosage, Lactic Acid chemistry, Lignans administration & dosage, Nanoparticles, Polyethylene Glycols chemistry, Polymers chemistry
- Abstract
The combination chemotherapy is an important protocol in cancer therapy. Honokiol shows synergistic anticancer effect with doxorubicin. In this paper, honokiol and doxorubicin co-loaded MPEG-PLA nanoparticles were prepared. The particle size, morphology, in vitro release profile, cytotoxicity and cell proliferation study were studied in detail. The results indicated that honokiol and doxorubicin could be efficiently loaded into MPEG-PLA nanoparticles simultaneously, and could be released out in an extended period in vitro. Meanwhile, honokiol and doxorubicin in MPEG-PLA nanoparticle could efficiently suppress cancer cell proliferation in vitro. The described honokiol and doxorubicin co-loaded MPEG-PLA nanoparticle might be a novel anticancer agent.
- Published
- 2010
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15. Polymeric matrix for drug delivery: honokiol-loaded PCL-PEG-PCL nanoparticles in PEG-PCL-PEG thermosensitive hydrogel.
- Author
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Gou M, Gong C, Zhang J, Wang X, Wang X, Gu Y, Guo G, Chen L, Luo F, Zhao X, Wei Y, and Qian Z
- Subjects
- Animals, Biocompatible Materials pharmacology, Hydrophobic and Hydrophilic Interactions, Mice, Polyesters chemical synthesis, Polyethylene Glycols chemical synthesis, Biphenyl Compounds pharmacology, Drug Delivery Systems, Hydrogel, Polyethylene Glycol Dimethacrylate chemistry, Lignans pharmacology, Nanoparticles chemistry, Polyesters chemistry, Polyethylene Glycols chemistry, Temperature
- Abstract
In this article, we demonstrated a novel injectable polymer matrix: honokiol (HK) loaded poly (epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles in thermosensitive poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) hydrogel for the drug local delivery. First, HK, as a model hydrophobic drug, was loaded into PCL-PEG-PCL nanoparticles by emulsion solvent evaporation method to overcome its poor water solubility. Then, the HK-loaded PCEC nanoparticles (HK-PCEC) were incorporated into thermosensitive PEG-PCL-PEG hydrogel, which was sol at low temperature and could gel as a depot for sustained release of drug in situ after topical injection. The HK-PCEC incorporated PECE hydrogel (HK-PCEC-PECE) was biodegradable and could be gradually eliminated from the injection site in about 2 weeks after subcutaneously injected into mice. The in vitro release studies indicated that HK could be released from HK-PCEC and HK-PCEC-PECE in a sustained manner. Such biodegradable smart drug-delivery system might have great potential application in injectable hydrophobic drug local delivery system.
- Published
- 2010
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16. Preparation of MPEG-PLA nanoparticle for honokiol delivery in vitro.
- Author
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Zheng X, Kan B, Gou M, Fu S, Zhang J, Men K, Chen L, Luo F, Zhao Y, Zhao X, Wei Y, and Qian Z
- Subjects
- Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Chemistry, Pharmaceutical, Chromatography, Gel, Dose-Response Relationship, Drug, Female, Hemolysis drug effects, Humans, Kinetics, Magnetic Resonance Spectroscopy, Molecular Structure, Molecular Weight, Nanotechnology, Ovarian Neoplasms pathology, Particle Size, Polyesters toxicity, Polyethylene Glycols toxicity, Solubility, Solvents chemistry, Surface Properties, Technology, Pharmaceutical methods, Antineoplastic Agents, Phytogenic chemistry, Biphenyl Compounds chemistry, Drug Carriers, Lignans chemistry, Nanoparticles, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
Honokiol (HK) shows potential application in cancer treatment, but its poor water solubility restricts clinical application greatly. In this paper, monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) was synthesized by ring-opening polymerization and processed into nanoparticle for honokiol delivery. Chemical structure of the synthesized polymer was confirmed by (1)H NMR, and its molecular weight was determined by gel permeation chromatography (GPC). Honokiol loaded MPEG-PLA nanoparticles were prepared by solvent extract method. And particle size distribution, morphology, drug loading, drug release profile and anticancer activity in vitro were studied in detail. The described honokiol loaded MPEG-PLA nanoparticles in this paper might be a novel formulation for honokiol delivery., (Copyright 2009 Elsevier B.V. All rights reserved.)
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- 2010
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17. Acute toxicity and genotoxicity studies on poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) nanomaterials.
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Huang Y, Gao H, Gou M, Ye H, Liu Y, Gao Y, Peng F, Qian Z, Cen X, and Zhao Y
- Subjects
- Animals, Female, Male, Mutagenicity Tests, Rats, Rats, Sprague-Dawley, Drug Carriers toxicity, Mutagens toxicity, Nanostructures toxicity, Polyesters toxicity, Polyethylene Glycols toxicity
- Abstract
In the present study, we prepared poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) nanomaterials by solvent-extraction method. The obtained PCEC nanomaterials were studied extensively for acute toxicity and genotoxicity using bacterial reverse mutation test (Ames test), chromosomal aberration test and mouse micronucleus test. All of the Sprague-Dawley rats did not show any mortality and clinical signs of toxicity after intravenous injection at the level of 2.4g/kg body weight. Thus, the LD(50) of PCEC nanomaterials was determined to be greater than 2.4g/kg. In Ames test, PCEC nanomaterials were negative in Salmonellatyphimurium strains TA97, TA98, TA100, TA102, and TA1535 with or without metabolic activation. PCEC nanomaterials did not induce chromosomal aberrations in cultured Chinese hamster lung cells up to 5000mug/mL with or without metabolic activation. Micronucleus assay demonstrated that PCEC nanomaterials did not significantly increase micronucleated polychromatic erythrocytes (MNPCE) in the bone marrow of ICR mice or suppress bone marrow, indicating they did not cause chromosome aberrations. In conclusion, our results indicated that PCEC nanomaterials did not cause any acute toxicity and genotoxicity in our experimental conditions. Its potential to be a candidate of drug carrier is worth being further investigated., (Copyright © 2010 Elsevier B.V. All rights reserved.)
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- 2010
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18. Biodegradable in situ gel-forming controlled drug delivery system based on thermosensitive PCL-PEG-PCL hydrogel. Part 2: sol-gel-sol transition and drug delivery behavior.
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Gong C, Shi S, Wu L, Gou M, Yin Q, Guo Q, Dong P, Zhang F, Luo F, Zhao X, Wei Y, and Qian Z
- Subjects
- Anesthetics, Local administration & dosage, Anesthetics, Local chemistry, Animals, Biocompatible Materials chemistry, Biocompatible Materials metabolism, Lidocaine administration & dosage, Lidocaine chemistry, Materials Testing, Micelles, Molecular Weight, Pain Measurement, Phase Transition, Porosity, Rats, Rats, Sprague-Dawley, Rheology, Temperature, Absorbable Implants, Drug Carriers chemistry, Drug Carriers metabolism, Drug Delivery Systems, Hydrogel, Polyethylene Glycol Dimethacrylate chemistry, Hydrogel, Polyethylene Glycol Dimethacrylate metabolism, Polyesters chemistry, Polyesters metabolism, Polyethylene Glycols chemistry, Polyethylene Glycols metabolism, Polymers chemistry, Polymers metabolism
- Abstract
In this work, a biodegradable and injectable in situ gel-forming controlled drug delivery system based on thermosensitive poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) hydrogel was studied. The prepared PCEC hydrogel undergoes temperature-dependent sol-gel-sol transition, which is a flowing sol at ambient temperature and turns into a non-flowing gel at around physiological body temperature. Furthermore, the sol-gel phase transition mechanism was investigated using (13)C-nuclear magnetic resonance imaging and a laser diffraction particle size analyzer. The in vitro release behaviors of several model drugs, including a hydrophilic small-molecule drug, a hydrophobic small-molecule drug and a macromolecular protein drug, from PCEC hydrogel were also investigated in detail. The results showed that the model drugs could be released from the PCEC hydrogel system over a sustained period. In addition, an anaesthesia assay was conducted using the tail flick latency (TFL) test to evaluate the in vivo controlled drug delivery effect of the PCEC hydrogel system. In the TFL assay, a lidocaine-loaded PCEC hydrogel produced significantly longer-lasting local anaesthetic effects compared with lidocaine aqueous solution at the same dose. Therefore, PCEC hydrogel is promising for use as an injectable local drug delivery system.
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- 2009
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19. Poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) nanoparticles: preparation, characterization, and application in doxorubicin delivery.
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Gou M, Zheng X, Men K, Zhang J, Zheng L, Wang X, Luo F, Zhao Y, Zhao X, Wei Y, and Qian Z
- Subjects
- Animals, Antibiotics, Antineoplastic toxicity, Cell Line, Doxorubicin toxicity, Drug Carriers, Female, Humans, Hydrogen-Ion Concentration, Mice, Mice, Inbred BALB C, Nanoparticles toxicity, Neoplasms drug therapy, Rats, Antibiotics, Antineoplastic chemistry, Doxorubicin chemistry, Nanoparticles chemistry, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
Biodegradable poly(epsilon-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymer nanoparticles showed potential application in drug delivery systems. In this article, monodisperse poly(epsilon-caprolactone)/poly(ethylene glycol)/poly(epsilon-caprolactone) (PCL/PEG/PCL, PCEC) nanoparticles, approximately 40 nm, were prepared by solvent extraction method using acetone as the organic solvent. These PCL/PEG/PCL nanoparticles did not induce hemolysis in vitro and did not show toxicity in vitro or in vivo. The prepared PCL/PEG/PCL nanoparticles were employed to load doxorubicin by a pH-induced self-assembly method. In vitro release study indicated that doxorubicin release from nanoparticles at pH 5.5 was faster than that at pH 7.0. The encapsulation of doxorubicin in PCL/PEG/PCL nanoparticles enhanced the cytotoxicity of doxorubicin on a C-26 cell line in vitro. Meanwhile, compared with free doxorubicin, doxorubicin in nanoparticles could more efficiently treat mice bearing subcutaneous C-26 tumors. The doxorubicin-loaded PCL/PEG/PCL nanoparticles might be a novel doxorubicin formulation for cancer therapy.
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- 2009
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20. Self-assembled hydrophobic honokiol loaded MPEG-PCL diblock copolymer micelles.
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Gou M, Zheng X, Men K, Zhang J, Wang B, Lv L, Wang X, Zhao Y, Luo F, Chen L, Zhao X, Wei Y, and Qian Z
- Subjects
- Animals, Chromatography, Gel, Chromatography, High Pressure Liquid, Microscopy, Electron, Transmission, Rats, Rats, Sprague-Dawley, X-Ray Diffraction, Micelles, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
Purpose: Honokiol showed potential application in cancer treatment, but its poor water solubility restricts its clinical application greatly. So, we designed a self-assembled monomethoxy poly(ethylene glycol)-poly(epsilon-caprolactone) (MPEG-PCL) micelle to load honokiol to overcome its poor water solubility., Methods: We synthesized MPEG-PCL diblock copolymer that could self-assemble into monodisperse micelles at the particle size of ca.18 nm in water. Honokiol was loaded into MPEG-PCL micelle by direct dissolution method assisted by ultrasound, without any surfactants, organic solvents, and vigorous stirring., Results: The blank MPEG-PCL micelles (100 mg/mL) did not induce any hemolysis in vitro and showed very low toxicity ex vivo and in vivo. Honokiol could be molecularly incorporated into MPEG-PCL micelles at the drug loading of about 20% by direct dissolution method assisted by ultrasound. After loaded into MPEG-PCL micelles, honokiol maintained its molecular structure and anticancer activity in vitro. Honokiol could be sustained released from MPEG-PCL micelles in vitro. The honokiol loaded MPEG-PCL micelles could be lyophilized without any adjuvant., Conclusion: The prepared honokiol formulation based on self-assembled MPEG-PCL micelle was stable, safe, effective, easy to produce and scale up, and showed potential clinical application.
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- 2009
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21. Poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) nanoparticles for honokiol delivery in vitro.
- Author
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Gou M, Zheng L, Peng X, Men K, Zheng X, Zeng S, Guo G, Luo F, Zhao X, Chen L, Wei Y, and Qian Z
- Subjects
- Animals, Antineoplastic Agents, Phytogenic administration & dosage, Cell Line, Cell Line, Tumor, Drug Carriers chemistry, Drugs, Chinese Herbal administration & dosage, Erythrocytes drug effects, Erythrocytes metabolism, Female, Hemolysis drug effects, Humans, Nanoparticles, Ovarian Neoplasms drug therapy, Ovarian Neoplasms pathology, Particle Size, Rabbits, Solvents chemistry, Biphenyl Compounds administration & dosage, Lignans administration & dosage, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
In this article, poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL, PCEC) nanoparticles were successfully prepared for honokiol delivery in vitro. Blank or honokiol loaded PCL-PEG-PCL nanoparticles were prepared in moderate condition by solvent diffusion method without using any surfactants. The prepared blank PCL-PEG-PCL nanoparticles are mono-dispersed and smaller than 200 nm. The particle size increased with increase in polymer concentration and oil-water (O/W) ratio. The prepared PCL-PEG-PCL nanoparticles (40 mg/mL, ca. 106 nm) did not induce hemolysis in vitro. And the 50% inhibiting concentration (IC50) of it (48 h) on HEK293 cells was higher than 5 mg/mL. Honokiol could be efficiently loaded into PCL-PEG-PCL nanoparticles and released from these nanoparticles in an extended period in vitro. After honokiol (HK) was entrapped into PCL-PEG-PCL nanoparticles, the particle size increased with the increase in HK/PCEC mass ratio in feed, and the encapsulated honokiol retained potent anticancer activity in vitro. The PCL-PEG-PCL nanoparticle was suitable for honokiol delivery, and such honokiol loaded PCL-PEG-PCL nanoparticle was a novel honokiol formulation.
- Published
- 2009
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22. Self-assembled honokiol-loaded micelles based on poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) copolymer.
- Author
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Wei X, Gong C, Shi S, Fu S, Men K, Zeng S, Zheng X, Gou M, Chen L, Qiu L, and Qian Z
- Subjects
- Antineoplastic Agents, Phytogenic administration & dosage, Cell Line, Tumor, Delayed-Action Preparations, Drug Carriers chemistry, Drug Delivery Systems, Humans, Lasers, Lung Neoplasms drug therapy, Micelles, Microscopy, Atomic Force, Particle Size, Temperature, Biphenyl Compounds administration & dosage, Lignans administration & dosage, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
Self-assembled polymeric micelles are widely applied in drug delivery system (DDS). In this study, honokiol (HK) loaded micelles were prepared from biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) copolymers. Micelles were prepared by self-assembly of triblock copolymer PCEC in distilled water triggered by its amphiphilic character without any organic solvent. Drug loading and encapsulation efficiency were determined by adjusting the weight ratio of HK and PCEC. The particle size and zeta potential distribution of obtained micelles were determined using Malvern laser particle sizer, and spherical geometry were observed on atomic force microscope (AFM). Otherwise, the thermo-sensitivity of honokiol-loaded micelles was monitored. And the cytotoxicity results of drug loaded micelles showed that the encapsulated honokiol remained potent antitumor effect. Moreover, in vitro release profile demonstrated a significant difference between rapid release of free honokiol and much slower and sustained release of HK-loaded micelles. These results suggested that we have successfully prepared honokiol-loaded micelles in an improved method which is safer and more efficient. The prepared micelles might be potential carriers for honokiol delivery in cancer chemotherapy.
- Published
- 2009
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23. Synthesis and characterization of PEG-PCL-PEG thermosensitive hydrogel.
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Gong C, Shi S, Dong P, Kan B, Gou M, Wang X, Li X, Luo F, Zhao X, Wei Y, and Qian Z
- Subjects
- Animals, Cell Line, Delayed-Action Preparations, Drug Delivery Systems, Humans, Hydrophobic and Hydrophilic Interactions, Injections, Subcutaneous, Mice, Polyesters chemical synthesis, Polyesters toxicity, Polyethylene Glycols chemical synthesis, Polyethylene Glycols toxicity, Temperature, Toxicity Tests, Hydrogels, Phase Transition, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
In this work, a series of biodegradable triblock poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers were successfully synthesized by ring-opening copolymerization, and were characterized by (1)H NMR, FT-IR, GPC, and DSC. Aqueous solutions of PECE copolymers underwent thermosensitive sol-gel-sol transition as temperature increases when the concentration was above corresponding critical gel concentration (CGC). Sol-gel-sol phase transition diagrams were recorded using test tube inverting method, which depended on hydrophilic/hydrophobic balance in macromolecular structure, as well as some other factors, including topology of triblock copolymers and solution composition of the hydrogel. As a result, the sol-gel-sol transition temperature range could be varied, which might be very useful for its application as injectable drug delivery systems. The in vivo gel formation and degradation behavior was conducted by injecting aqueous PECE solution into KunMing mice subcutaneously. In vitro degradation behavior, in vitro drug release behavior, and cytotoxicity were also investigated in this paper. Therefore, owing to great thermosensitivity and biodegradability of these copolymers, PECE hydrogel is believed to be promising for in situ gel-forming controlled drug delivery system.
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- 2009
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24. Preparation of biodegradable polycaprolactone/poly (ethylene glycol)/polycaprolactone (PCEC) nanoparticles.
- Author
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Jia W, Gu Y, Gou M, Dai M, Li X, Kan B, Yang J, Song Q, Wei Y, and Qian Z
- Subjects
- Animals, Cattle, Microscopy, Electron, Scanning, Polyesters chemical synthesis, Polyesters chemistry, Polyethylene Glycols chemical synthesis, Polyethylene Glycols chemistry, Drug Delivery Systems, Nanoparticles, Polyesters administration & dosage, Polyethylene Glycols administration & dosage
- Abstract
Biodegradable polyetherester copolymer (PCL/PEG/PCL, PCEC) was synthesized by ring-opening polymerization of epsilon-caprolactone initiated by poly(ethylene glycol) (PEG). The PCEC nanoparticles were prepared by solvent diffusion method or w/o/w double emulsion method. The obtained particles' morphology was observed on scanning electron microscopy, and the particle size distribution was determined using Malvern laser particle sizer. Bovine serum albumin was used as the model water-soluble protein drug, which was successfully encapsulated in PCEC nanoparticles, the drug release behavior was studied in detail. The hydrolytic degradation behavior of the PCEC nanoparticles was also studied.
- Published
- 2008
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25. A novel injectable local hydrophobic drug delivery system: Biodegradable nanoparticles in thermo-sensitive hydrogel.
- Author
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Gou M, Li X, Dai M, Gong C, Wang X, Xie Y, Deng H, Chen L, Zhao X, Qian Z, and Wei Y
- Subjects
- Animals, Delayed-Action Preparations, Drug Delivery Systems, Emulsions, Hydrogels, Hydrophobic and Hydrophilic Interactions, Injections, Subcutaneous, Mice, Poloxamer chemistry, Solvents chemistry, Temperature, Biphenyl Compounds chemistry, Excipients chemistry, Lignans chemistry, Nanoparticles, Polyesters chemistry, Polyethylene Glycols chemistry
- Abstract
In this article, a novel local hydrophobic drug delivery system: nanoparticles in thermo-sensitive hydrogel, was demonstrated. First, honokiol, as a model hydrophobic drug, loaded poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) nanoparticles were prepared by emulsion solvent evaporation method, and then were incorporated into thermo-sensitive F127 hydrous matrix. The obtained injectable hydrophobic drug delivery system can act as a depot for sustained release of honokiol in situ. The lower critical solution temperature (LCST) of the composite matrix increases with increase in the mass of incorporated nanoparticles, or with decrease in the amount of residual organic solvent in the system. Honokiol release profile in vitro was studied, and the results showed that honokiol could be sustained released from the system. The described injectable drug delivery system might have great potential application for local delivery of hydrophobic drugs such as honokiol.
- Published
- 2008
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26. Preparation of mannan modified anionic PCL-PEG-PCL nanoparticles at one-step for bFGF antigen delivery to improve humoral immunity.
- Author
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Gou M, Dai M, Li X, Yang L, Huang M, Wang Y, Kan B, Lu Y, Wei Y, and Qian Z
- Subjects
- Animals, Antigens immunology, Fibroblast Growth Factor 2 immunology, Humans, Injections, Subcutaneous, Mice, Mice, Inbred C57BL, Antigens administration & dosage, Drug Delivery Systems, Fibroblast Growth Factor 2 administration & dosage, Immunoglobulin G biosynthesis, Mannans, Nanoparticles, Polyesters chemical synthesis, Polyethylene Glycols chemical synthesis
- Abstract
In this article, blank anionic poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) and anionic mannan modified PCEC (MPCEC) nanoparticles with nearly the same particle size and zeta potential were prepared by emulsion solvent evaporation method. Human basic fibroblast growth factor (bFGF) was absorbed onto anionic nanoparticles surface due to electrostatic interaction. The obtained bFGF-nanoparticles complexes were injected subcutaneously into C57BL/6 mice at 20 microg of bFGF/dose on week 0, 1, 2 and 3. The mice serum was collected on week 4, and bFGF-specific autoantibody total IgG, IgG1 and IgG2a titer in serum was determined by ELISA. The results indicated that the autoantibody IgG, IgG1 and IgG2a titer of the mice immunized by bFGF-MPCEC complexes were higher than that immunized by either bFGF-PCEC or bFGF-Alum. This phenomenon might be due to that mannan functionalized MPCEC nanoparticles could be targeted to dendritic cells (DCs) to improve humoral immunity. The prepared anionic mannan modified PCEC nanoparticles (MPCEC) might have great potential application in vaccine delivery systems.
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- 2008
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27. Basic fibroblast growth factor loaded biodegradable PCL-PEG-PCL copolymeric nanoparticles: preparation, in vitro release and immunogenicity study.
- Author
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Gou M, Dai M, Gu Y, Li X, Wen Y, Yang L, Wang K, Wei Y, and Qian Z
- Subjects
- Animals, Antibody Formation, Female, Fibroblast Growth Factor 2 immunology, Humans, Mice, Mice, Inbred BALB C, Microscopy, Electron, Scanning, Fibroblast Growth Factor 2 administration & dosage, Nanoparticles, Polyesters administration & dosage, Polyethylene Glycols administration & dosage
- Abstract
In this article, human basic fibroblast growth factor (bFGF) loaded PCL-PEG-PCL (PCEC) nanoparticles were prepared by modified W1/O/W2 double emulsion solvent evaporation method. The bFGF encapsulated in PCEC nanoparticles could be released in sustained release behavior in vitro. After subcutaneous single-dose injection of bFGF loaded PCEC nanoparticles at 20 microg of bFGF per dose in mice, the anti-bFGF special autoantibody IgG continued to grow until 8 weeks after the immunization and was still kept at high level at week 11. At the same time, HK293 cell viability assay in vitro indicated that the cytotoxicity of blank PCEC nanoparticles was low but dose dependent. For some success in controlling tumor growth had been met by neutralizing bFGF reported previously, the bFGF loaded PCEC nanoparticles prepared in this paper might have potential application as anti-tumor vaccine.
- Published
- 2008
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28. Acute oral toxicity evaluation of biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA).
- Author
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Chen X, Qian Z, Gou M, Chao G, Zhang Y, Gu Y, Huang M, Wang J, Pan Y, Wei Y, Chen J, and Tu M
- Subjects
- Absorbable Implants, Administration, Oral, Animals, Female, Hydrogels administration & dosage, Hydrogels chemistry, Hydrogen-Ion Concentration, Male, Mice, Mice, Inbred BALB C, Organ Specificity, Polyesters administration & dosage, Polyesters chemistry, Polyethylene Glycols administration & dosage, Polyethylene Glycols chemistry, Polymethacrylic Acids administration & dosage, Polymethacrylic Acids chemistry, Hydrogels toxicity, Polyesters toxicity, Polyethylene Glycols toxicity, Polymethacrylic Acids toxicity
- Abstract
In this article, a novel biodegradable and pH-sensitive hydrogel based on polycaprolactone, poly(ethylene glycol) and methylacrylic acid (MAA), was prepared by UV-initiated free radical polymerization. The obtained hydrogel was characterized by (1)H NMR and FTIR. The acute toxicity tests and histopathological study were performed in BALB/c mice. In acute oral toxicity test, mice were orally administered with a total 15 g/kg body weight (b.w.) of P(CL-MAA-EG) hydrogels, and were observed continuously for 14 days. For histopathologic study, samples including heart, liver, lung, kidneys, spleen, stomach, and intestine, were histochemically prepared and stained with hematoxylin-eosin for histopathologic examination. No mortality or significant signs of acute toxicity was observed during the whole observation period, and no macroscopic alteration was found in the organs. Histopathological analysis of various organs also did not show any significant pathological changes. Thus, the maximal tolerance dose of P(CL-MAA-EG) hydrogels was calculated to be higher than 15 g/kg b.w. in BALB/c mice. It was suggested that the studied P(CL-MAA-EG) hydrogel in this article were nontoxic after acute oral administration and it might be a promising candidate as a novel oral drug carrier., ((c) 2007 Wiley Periodicals, Inc.)
- Published
- 2008
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29. Synthesis, characterization and hydrolytic degradation study of polyetheresteramide copolymers based on epsilon-caprolactone, 6-aminocaproic acid, and poly(ethylene glycol).
- Author
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Liu C, Qian Z, Jia W, Huang M, Chao G, Gong C, Deng H, Wen Y, Yang J, Gou M, and Tu M
- Subjects
- Absorption, Hydrogen-Ion Concentration, Hydrolysis, Materials Testing, Models, Biological, Water metabolism, Aminocaproic Acid chemistry, Caproates chemistry, Lactones chemistry, Polyethylene Glycols chemistry, Polymers chemical synthesis, Polymers metabolism
- Abstract
In this paper, a new kind of biodegradable aliphatic polyetheresteramide copolymers (PEEA) based on epsilon-caprolactone, 6-aminocaproic acid, and poly(ethylene glycol) (PEG) were synthesized by melt polymerization method. The obtained copolymers were characterized by 1H-NMR. The thermal properties of PEEA copolymers were studied by DSC and TGA/DTA under nitrogen atmosphere. The water absorption and hydrolytic degradation behavior was also studied in detail. With the increase in PEG content or the decrease in caprolactone content, the water absorption of the copolymers increased accordingly. For the hydrolytic degradation behavior, with the increase in PEG content or caprolactone content, the degradation rate increased then.
- Published
- 2007
- Full Text
- View/download PDF
30. Synthesis, characterization and hydrolytic degradation of degradable poly(butylene terephthalate)/poly(ethylene glycol) (PBT/PEG) copolymers.
- Author
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Chao G, Fan L, Jia W, Qian Z, Gu Y, Liu C, Ni X, Li J, Deng H, Gong C, Gou M, Lei K, Huang A, Huang C, Yang J, Kan B, and Tu M
- Subjects
- Crystallization, Esterification, Hydrogen-Ion Concentration, Hydrolysis, Magnetic Resonance Spectroscopy, Materials Testing, Molecular Weight, Thermodynamics, Biocompatible Materials chemical synthesis, Biocompatible Materials chemistry, Polyesters chemical synthesis, Polyesters chemistry, Polyethylene Glycols chemical synthesis, Polyethylene Glycols chemistry
- Abstract
Hydrolytic degradable PBT/PEG copolymer was synthesized by macromolecular transesterification method from PBT and PEG macromonomers. The resultant copolymers were characterized by (1)H-NMR and GPC. The non-isothermal crystallization behavior of these copolymers was studied by differential scanning calorimetry (DSC). The water absorption and hydrolytic degradation behavior of PBT/PEG copolymers were also studied in detail.
- Published
- 2007
- Full Text
- View/download PDF
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