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ABSTRACT: A flexible and fibrous composite scaffold composed of poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) and 30 wt.% nano-hydroxyapatite (n-HA) was fabricated through electrospinning. In the present study, we investigated its in vitro and in vivo performance by means of hydrolytic degradation, muscle pouch implantation, as well as repair the calvarial defects in New Zealand white rabbits. The results demonstrated that the degradable scaffold held good biocompatibility. Qualitative analysis of bone regeneration process was performed by radiological examination and histological analysis. The results indicated that new bone formed originally from the margin of host bone, and then grew toward the center of defects. Moreover, the quantitative determination of newly formed bone was performed using statistical analysis of histological sections at predetermined time points. At 20th week, the defects of treatment group were covered with the new solid cortical bone. In comparison, the control group was filled with a large amount of cancelous bone and bone marrow. It suggested that the composite scaffold had better activity of guided bone regeneration than that of self-healing. So the electrospun PCEC/n-HA fibrous scaffold had the great potential application in bone tissue engineering.
Biomaterials 08/2012; 33(33):8363-71. · 7.40 Impact Factor
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ABSTRACT: A novel three-component biomimetic hydrogel composite was successfully prepared in this study, which was composed of triblock PEG-PCL-PEG copolymer (PECE), collagen and nano-hydroxyapatite (n-HA). The microstructure and thermo-responsibility of the obtained PECE/Collagen/n-HA hydrogel composite were characterized. Scanning electronic microscopy (SEM) showed that the composite exhibited an interconnected porous structure. The rheological analysis revealed that the composite existed good thermo-sensitivity. In vivo biocompatibility and biodegradability was investigated by implanting the hydrogel composite in muscle pouches of rats for 3, 7, and 14 days. Moreover, the osteogenic capacity was evaluated by means of implanting the composite material in cranial defects of New Zealand White rabbits for 4, 12 and 20 weeks. In vivo performances confirmed that the biodegradable PECE/Collagen/n-HA hydrogel composite had good biocompatibility and better performance in guided bone regeneration than the self-healing process. Thus the thermal-response PECE/Collagen/n-HA hydrogel composite had the great potential in bone tissue engineering.
Biomaterials 03/2012; 33(19):4801-9. · 7.40 Impact Factor
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ABSTRACT: The aim of this study was to prepare PCL-PEG-PCL (PCEC) microspheres to protect camptothecin from hydrolysis, to extend its release time and to enhance its treatment efficacy on colorectal peritoneal carcinomatosis and tumor growth in mice. Camptothecin (CPT)-loaded PCL-PEG-PCL (PCEC) microspheres were prepared by oil-in-water emulsion solvent evaporation method. The particle size, morphological characteristics, encapsulation efficiency, in vitro drug release studies and in vitro cytotoxicity of CPT-loaded PCEC microspheres have been investigated. In vivo studies were carried out on Balb/c male mice bearing colorectal peritoneal carcinomatosis. CPT-loaded PCEC microspheres were applied to abdominal cavity of mice once a week. Free CPT was used as a positive control. On 14th day of treatment, mice were sacrificed and antitumor activities of CPT-loaded PCEC microspheres were evaluated. Compared with control group, a significant decrease in the number of tumor nodes was observed in group treated with CPT-loaded PCEC microspheres. Immunohistochemistry staining of tumor tissues with CD34 revealed that MVD positive cells were significantly reduced in CPT-loaded PCEC microspheres treated group in contrast to other groups (P<0.05). The CPT-loaded PCEC microspheres were considered potentially useful to treat the abdominal metastases of colon carcinoma.
Cancer letters 08/2011; 312(2):189-96. · 4.86 Impact Factor
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ABSTRACT: The purpose of this work was to develop implantable curcumin-loaded poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) nanofibers, which might have potential application in cancer therapy. Curcumin was incorporated into biodegradable PCEC nanofibers by electrospinning method. The surface morphology of the composite nanofibers was characterized on Scanning Electron Microscope (SEM). The average diameter of the nanofibers was 2.3-4.5μm. In vitro release behavior of curcumin from the fiber mats was also studied in detail. The in vitro cytotoxicity assay showed that the PCEC fibers themselves did not affect the growth of rat Glioma 9L cells. Antitumor activity of the curcumin-loaded fibers against the cells was kept over the whole experiment process, while the antitumor activity of pure curcumin disappeared within 48 h. These results strongly suggested that the curcumin/PCEC composite nanofibers might have potential application for postoperative chemotherapy of brain cancers.
Nanoscale 08/2011; 3(9):3825-32. · 5.91 Impact Factor
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ABSTRACT: In this study, nano-hydroxyapatite/poly(vinyl alcohol) (n-HA/PVA) composite membranes were prepared by solvent casting and evaporation method. The morphology, mechanical properties, water absorption behavior, contact angle measurement and biocompatibility of these membranes were examined by SEM, FTIR, XRD, MTT assay and etc. The results demonstrate that the surface of composite membranes is suitable for the adhesion and proliferation of osteogenic cells, and that n-HA and PVA are in uniform distribution when the content of n-HA is less than 20 wt%. Tests of swelling behavior and water contact angle show that the incorporation of n-HA into PVA matrix significantly reduces its hydrophilicity. Mechanical tests reveal that the addition of n-HA nanoparticles reduces tensile strength and elongation rate but increases Young's modulus of composite membranes. Cell attachment test and MTT assay prove that n-HA/PVA composite membranes have good biocompatibility. Therefore, the n-HA/PVA composite membranes possess potential application for guided bone regeneration (GBR).
Journal of Biomedical Nanotechnology 08/2011; 7(4):549-57. · 4.22 Impact Factor
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ABSTRACT: In this study, poly(lactic acid) (PLA) ultrafine fibers have been prepared by electrospinning method using mix-solvent. The results showed that the variation of solvent ratio (N,N-dimethylformamide (DMF)/Dichloromethane (DCM)) could change the surface morphology of PLA nanofibers. By adjusting the solvent ratio, the quercetin release rate from the fiber membranes could be controlled. Furthermore, by adjusting the PLA concentration, the nanofibers without beads could be obtained. After addition of quercetin to polymer solution, the spindle-shaped beads on the fiber disappeared, but surface morphology of the fiber changed little with increase in quercetin dosage, and the release rate of quercetin increased with increase of quercetin dosage.
Journal of Nanoscience and Nanotechnology 04/2011; 11(4):3659-68. · 1.56 Impact Factor
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ABSTRACT: In this paper, the poly(vinyl alcohol)/poly(epsilon-caprolactone)-PEG-poly(epsilon-caprolactone)/nano-hydroxyapatite (PVA/PCEC/n-HA) composite membranes were prepared by solution casting and evaporation methods. The effect of n-HA content on the properties of the composite membranes was studied. The PVA/PCEC/n-HA composite membranes were analyzed by FTIR spectroscopy, X-ray diffraction, water content measurement, contact angle, mechanical test, scanning electron microscopy. The results showed that the surface roughness of the composite membranes increased with the increase of n-HA contents. The n-HA content had obvious influence on the swelling ratio, tensile strength and elongation rate of the composite membranes. With the increase of n-HA contents, the swelling ratio increased at first, and then decreased; tensile strength and elongation rate decreased gradually. The PVA/PCEC/n-HA composite membranes may be applied in the field of tissue engineering.
Journal of Nanoscience and Nanotechnology 03/2011; 11(3):2354-60. · 1.56 Impact Factor
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ABSTRACT: Self-assembled polymeric micelles are widely applied in drug delivery system. In this study, Tacrolimus (FK506) loaded micelles were prepared based on biodegradable poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCEC) copolymers. Micelles were prepared by self-assembly of triblock copolymer PCEC in distilled water triggered by its amphiphilic characteristics. Drug loading and encapsulation efficiency were determined by adjusting the weight ratio of FK506 and PCEC. The particle size distribution and variation of obtained micelles were determined using Malvern laser particle size analyzer, while the spherical geometry was observed on transmission electron microscope (TEM), and the crystallographic assays were fulfilled by X-ray diffractometer (XRD). Besides, in vitro release profile demonstrated a significant difference between rapid release of free Tacrolimus and much slower and sustained release of FK506 loaded micelles. These results suggested that we have successfully prepared Tacrolimus loaded micelles in an improved method which is safer and more efficient. The prepared micelles might be potential carriers for Tacrolimus delivery in immunosuppressive therapy.
International journal of pharmaceutics 01/2011; 407(1-2):184-9. · 2.96 Impact Factor
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ABSTRACT: Polylactide (PLA) electrospun fibers have been reported as a scaffold for bone tissue engineering application, however, the great hydrophobicity limits its broad application. In this study, the hybrid amphiphilic poly(ethylene glycol) (PEG)/hydrophobic PLA fibrous scaffolds exhibited improved morphology with regular and continuous fibers compared to corresponding blank PLA fiber mats. The prepared PEG/PLA fibrous scaffolds favored mesenchymal stem cell (MSC) attachment and proliferation by providing an interconnected porous extracellular environment. Meanwhile, MSCs can penetrate into the fibrous scaffold through the interstitial pores and integrate well with the surrounding fibers, which is very important for favorable application in tissue engineering. More importantly, the electrospun hybrid PEG/PLA fibrous scaffolds can enhance MSCs to differentiate into bone-associated cells by comprehensively evaluating the representative markers of the osteogenic procedure with messenger ribonucleic acid quantitation and protein analysis. MSCs on the PEG/PLA fibrous scaffolds presented better differentiation potential with higher messenger ribonucleic acid expression of the earliest osteogenic marker Cbfa-1 and mid-stage osteogenic marker Col I. The significantly higher alkaline phosphatase activity of the PEG/PLA fibrous scaffolds indicated that these can enhance the differentiation of MSCs into osteoblast-like cells. Furthermore, the higher messenger ribonucleic acid level of the late osteogenic differentiation markers OCN (osteocalcin) and OPN (osteopontin), accompanied by the positive Alizarin red S staining, showed better maturation of osteogenic induction on the PEG/PLA fibrous scaffolds at the mineralization stage of differentiation. After transplantation into the thigh muscle pouches of rats, and evaluating the inflammatory cells surrounding the scaffolds and the physiological characteristics of the surrounding tissues, the PEG/PLA scaffolds presented good biocompatibility. Based on the good cellular response and excellent osteogenic potential in vitro, as well as the biocompatibility with the surrounding tissues in vivo, the electrospun PEG/PLA fibrous scaffolds could be one of the most promising candidates in bone tissue engineering.
International Journal of Nanomedicine 01/2011; 6:3065-75. · 3.13 Impact Factor
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ABSTRACT: In this work, three-dimensional (3-D) porous scaffolds based on poly(ε-caprolactone)−poly(ethylene glycol)−poly(ε-caprolactone) (PCL-PEG-PCL, PCEC) and nano-hydroxyapatite (n-HA) were prepared by the electrospinning method. The physical−chemical properties of the composite membranes were investigated by Fourier transform infrared spectroscopy, X-ray diffraction, differential scanning calorimetry, water contact angle measurements, and a tensile test. Morphological study using scanning electron microscopy showed that the average fiber diameter decreased from about 1 μm (for pure PCEC membrane) to 0.6 μm (containing 30% HA) with the increase of HA contents. At high content (>10%), agglomeration of HA can be observed on the surfaces of composite membranes fibers, which decreased the tensile strength and elongation rate of the samples. In vitro osteoblast cell culture demonstrated the electrospun n-HA/PCEC composite scaffolds could provide a suitable environment for cell attachment, and MTT results revealed the scaffolds had good biocompatibility and nontoxicity. The results indicated that such n-HA/PCEC fibrous membranes might have potential applications in tissue engineering field.
10/2010;
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ABSTRACT: In this work a series of nano-hydroxyapatite/poly(epsilon-caprolactone)-Pluronic-poly(epsilon-caprolactone) (n-HA/ PCFC) nanocomposites has been prepared. Thermal properties of the nanocomposites are studied by thermogravimetry analysis (TGA) and differential scanning calorimetry (DSC). The TGA/DTG results reveal that thermal stability of n-HA/PCFC nanocomposites is improved by incorporation of n-HA into polymer matrix, and the thermo-degradation temperature increased slightly with increasing HA loading. DSC results show that the glass transition temperature (T(g)) changed by the addition of n-HA. The mechanical properties of the nanocomposites are investigated by tensile testing. The morphology for tensile-fractured surfaces of nanocomposites is observed by scanning electron microscopy. The effect of n-HA contents of nanocomposites on tensile strength and morphology is also discussed.
Journal of Biomaterials Science Polymer Edition 06/2010; · 1.69 Impact Factor
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Shaozhi Fu,
Gang Guo,
Xinlong Wang,
Liangxue Zhou,
Tingting Liu,
Pengwei Dong,
Feng Luo,
Yingchun Gu,
Xingyu Shi,
Xia Zhao,
Yuquan Wei,
Zhiyong Qian
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ABSTRACT: In this paper, a new kind of polymeric nanocomposite materials based on nano-hydroxyapatite (n-HA) and PCL-Pluronic-PCL (PCFC) copolymer were prepared by in situ combination method. Firstly, the PCFC copolymer was synthesized by ring-opening polymerization of epsilon-caprolactone initiated by Pluronic (PEG-PPG-PEG); Secondly, n-HA powder were combined with PCFC to form polymeric composites in the presence of hexamethylene diisocyanate (HDI). The obtained composites were characterized by 1H-NMR, FTIR, XRD, TEM, SEM, DTA/TGA, and tensile testing. The results revealed that n-HA could be dispersed into polymer matrix uniformly, and the n-HA/PCFC composite showed great mechanical properties when the content of n-HA was 10 wt%. The microstructure and thermal properties of the composites were discussed in the paper too. The experimental results suggested that this polymeric nanocomposite might have great potential application in the field of tissue engineering.
Journal of Nanoscience and Nanotechnology 02/2010; 10(2):711-8. · 1.56 Impact Factor
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XiuLing Zheng,
Bing Kan,
MaLing Gou, ShaoZhi Fu,
Juan Zhang,
Ke Men,
LiJuan Chen,
Feng Luo,
YingLan Zhao,
Xia Zhao,
YuQuan Wei,
ZhiYong Qian
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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.
International journal of pharmaceutics 11/2009; 386(1-2):262-7. · 2.96 Impact Factor
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ABSTRACT: In this study, we synthesized a biodegradable triblock copolymer poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) by ring-opening copolymerization, and nanohydroxyapatite (n-HA) powder was prepared by a hydrothermal precipitation method. The obtained n-HA was incorporated into the PECE matrix to prepare injectable thermosensitive hydrogel nanocomposites. (1)H NMR, FT-IR, XRD, DSC, and TEM were used to investigate the properties of PECE copolymer and n-HA/PECE nanocomposites. The rheological measurements for n-HA/PECE nanocomposites revealed that the gelation temperature was approximately 36 degrees C. The sol-gel-sol transition behavior and phase transition diagrams were recorded through a test tube inverting method. The results showed that n-HA/PECE nanocomposites still had thermoresponsivity like that of PECE thermosensitive hydrogel. The morphology of the nanocomposites was observed by SEM; the results showed that the nanocomposites had a 3D network structure. In addition, the effects of n-HA contents on the properties of n-HA/PECE nanocomposites are also discussed in the paper. From the results, n-HA/PECE hydrogel is believed to be promising for injectable orthopedic tissue engineering due to its good thermosensitivity and injectability.
The Journal of Physical Chemistry B 11/2009; 113(52):16518-25. · 3.70 Impact Factor
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ABSTRACT: This paper prepared novel biodegradable and pH-sensitive microgels based on Poly(epsilon-caprolactone)-Pluronic-Poly(epsilon-caprolactone)-dimethacrylate (PCFC-DMA), Poly(ethylene glycol) dimethacrylate (PEG-DMA) and methylacrylic acid (MAA) cross-linked with N,N'-methylenebisacrylamide (BIS), initiated by NaHSO(3), K(2)S(2)O(8). The blank microgels were prepared by inversed-phase suspension polymerization method and pH sensitivity of microgels was characterized. Then the blank microgels were loaded with hydrophilic model drug vitamin-12 (VB-12) and in vitro drug release behaviour was also studied here.
Journal of Microencapsulation 11/2009; 26(7):642-8. · 1.55 Impact Factor
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ABSTRACT: Poly(epsilon-caprolactone)-poly(ethylene glycol) (PCL-PEG) copolymers are important synthetic biomedical materials with amphiphilicity, controlled biodegradability, and great biocompatibility. They have great potential application in the fields of nanotechnology, tissue engineering, pharmaceutics, and medicinal chemistry. This review introduced several aspects of PCL-PEG copolymers, including synthetic chemistry, PCL-PEG micro/nanoparticles, PCL-PEG hydrogels, and physicochemical and toxicological properties.
International journal of pharmaceutics 09/2009; 381(1):1-18. · 2.96 Impact Factor
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ABSTRACT: This study aims to develop a novel composite drug delivery system (CDDS) for hydrophobic honokiol delivery: honokiol loaded micelles in thermosensitive hydrogel (honokiol micelles/hydrogel) based on biodegradable poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) copolymers. In our work, we found that PECE copolymers with different molecular weight and PEG/PCL ratios could be administered to form micelles or thermosensitive hydrogel, respectively. Honokiol loaded PECE micelles (honokiol micelles) were prepared by self-assembly of biodegradable PECE copolymer (PEG5000-PCL5000-PEG5000) triggered by its amphiphilic characteristic assisted by ultrasonication without using any organic solvents and surfactants. Meanwhile, biodegradable and injectable thermosensitive PECE hydrogel (PEG550-PCL2400-PEG550) with a lower sol-gel transition temperature at around physiological temperature was also prepared successfully. Furthermore, the obtained honokiol micelles/hydrogel CDDS was a free-flowing sol at ambient temperature and became a nonflowing gel at body temperature. The cytotoxicity results showed that the CDDS was a safe carrier and the encapsulated honokiol retained its potent antitumor effect. In addition, the in vitro release profile demonstrated a significant difference between rapid release of free honokiol and much slower and sustained release of honokiol micelles/hydrogel. The results suggested that the CDDS might have great potential applications in cancer chemotherapy.
The Journal of Physical Chemistry B 08/2009; 113(30):10183-8. · 3.70 Impact Factor
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ABSTRACT: Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.
A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(epsilon-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 microg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.
The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.
BMC Biotechnology 03/2009; 9:8. · 2.35 Impact Factor
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Shuai Shi,
QingFa Guo,
Bing Kan, ShaoZhi Fu,
XiuHong Wang,
ChangYang Gong,
HongXin Deng,
Feng Luo,
Xia Zhao,
YuQuan Wei,
ZhiYong Qian
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ABSTRACT: Polyethyleneimine (PEI), a cationic polymer, is one of the successful and widely used vectors for non-viral gene transfection in vitro. However, its in vivo application was greatly limited due to its high cytotoxicity and short duration of gene expression. To improve its biocompatibility and transfection efficiency, PEI has been modified with PEG, folic acid, and chloroquine in order to improve biocompatibility and enhance targeting.
Poly(epsilon-caprolactone)-Pluronic-Poly(epsilon-caprolactone) (PCFC) was synthesized by ring-opening polymerization, and PCFC-g-PEI was obtained by Michael addition reaction with GMA-PCFC-GMA and polyethyleneimine (PEI, 25 kD). The prepared PCFC-g-PEI was characterized by 1H-NMR, SEC-MALLS. Meanwhile, DNA condensation, DNase I protection, the particle size and zeta potential of PCFC-g-PEI/DNA complexes were also determined. According to the results of flow cytometry and MTT assay, the synthesized PCFC-g-PEI, with considerable transfection efficiency, had obviously lower cytotoxicity against 293 T and A549 cell lines compared with that of PEI 25 kD.
The cytotoxicity and in vitro transfection study indicated that PCFC-g-PEI copolymer prepared in this paper was a novel gene delivery system with lower cytotoxicity and considerable transfection efficiency compared with commercial PEI (25 kD).
BMC Biotechnology 02/2009; 9:65. · 2.35 Impact Factor
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XiaWei Wei,
ChangYang Gong,
Shuai Shi, ShaoZhi Fu,
Ke Men,
Shi Zeng,
XiuLing Zheng,
MaLing Gou,
LiJuan Chen,
LiYan Qiu,
ZhiYong Qian
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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.
International journal of pharmaceutics 12/2008; 369(1-2):170-5. · 2.96 Impact Factor
