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1.
Materials (Basel) ; 17(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39124420

RESUMEN

Polyrotaxane (PR) has garnered increasing attention due to its unique structure and exceptional performance. In this study, a polypseudorotaxane (PPR) initiator was prepared through the self-assembly of bromine-capped Pluronic F68 and ß-cyclodextrins (ß-CD) in water. Polyrotaxane-containing triblock copolymers (PR copolymers) were successfully synthesized by atom transfer radical polymerization (ATRP) of butyl methacrylate (BMA) using the PPR initiator in the presence of Cu(I)Br/PMDETA. The structure of the PR copolymers was thoroughly characterized using infrared spectroscopy (IR), proton nuclear magnetic resonance (1H NMR), and gel permeation chromatography (GPC). The mobility of ß-CD in the PR copolymers was demonstrated through dielectric measurements. Mechanical tests, including tensile strength assessments, thermal mechanical analysis, and dynamic mechanical analysis, confirmed the excellent mechanical properties and good processability of the PR copolymer, attributed to the PBMA blocks. Furthermore, the mechanical properties were found to be modulated by the motility of the threaded ß-CDs. Consequently, the superior mechanical properties and the high mobility of the threaded ß-CDs suggest promising potential for the as-prepared PR polymer in various advanced applications.

2.
Int J Biol Macromol ; 267(Pt 2): 131667, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38636761

RESUMEN

A thiolated RGD was incorporated into the threaded allyl-ß-cyclodextrins (Allyl-ß-CDs) of the polyrotaxane (PR) through a thiol-ene click reaction, resulting in the formation of dynamic RGD ligands on the PR surface (dRGD-PR). When maintaining consistent RGD density and other physical properties, endothelial cells (ECs) cultured on dRGD-PR exhibited significantly increased cell proliferation and a larger cell spreading area compared to those on the non-dynamic RGD (nRGD-PCL). Furthermore, ECs on dRGD-PR demonstrated elevated expression levels of FAK, p-FAK, and p-AKT, along with a larger population of cells in the G2/M stage during cell cycle analysis, in contrast to cells on nRGD-PCL. These findings suggest that the movement of the RGD ligands may exert additional beneficial effects in promoting EC spreading and proliferation, beyond their essential adhesion and proliferation-promoting capabilities, possibly mediated by the RGD-integrin-FAK-AKT pathway. Moreover, in vitro vasculogenesis tests were conducted using two methods, revealing that ECs cultured on dRGD-PR exhibited much better vasculogenesis than nRGD-PCL in vitro. In vivo testing further demonstrated an increased presence of CD31-positive tissues on dRGD-PR. In conclusion, the enhanced EC spreading and proliferation resulting from the dynamic RGD ligands may contribute to improved in vitro vasculogenesis and in vivo vascularization.


Asunto(s)
Proliferación Celular , Ciclodextrinas , Oligopéptidos , Humanos , Adhesión Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ciclodextrinas/química , Ciclodextrinas/farmacología , Células Endoteliales/metabolismo , Células Endoteliales/efectos de los fármacos , Células Endoteliales/citología , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Ligandos , Neovascularización Fisiológica/efectos de los fármacos , Oligopéptidos/farmacología , Oligopéptidos/química , Poloxámero/química , Poloxámero/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Rotaxanos
3.
Tissue Eng Part C Methods ; 30(2): 53-62, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38019085

RESUMEN

The effect and mechanism of type III recombinant humanized collagen (hCOLIII) on human vascular endothelial EA.hy926 cells at the cellular and molecular levels were investigated. The impact of hCOLIII on the proliferation of EA.hy926 cells was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid assay, the effect of hCOLIII on cell migration was investigated by scratch assay, the impact of hCOLIII on cell cycle and apoptosis was detected by flow cytometry, the ability of hCOLIII to induce angiogenesis of EA.hy926 cells was evaluated by angiogenesis assay, and the effect of hCOLIII on vascular endothelial growth factor (VEGF) expression was detected by real-time reverse transcription-polymerase chain reaction analysis. The hCOLIII at concentrations of 0.5, 0.25, and 0.125 mg/mL all showed specific effects on the proliferation and migration of human vascular endothelial cells. It could also affect the cell cycle, increase the proliferation index, and increase the expression level of VEGF in human vascular endothelial cells. In the meantime, hCOLIII at the concentration of 0.5 mg/mL also showed a promoting effect on vessel formation. hCOLIII can potentially promote the endothelization process of blood vessels, mainly by affecting the proliferation, migration, and vascular-like structure of human endothelial cells. At the same time, hCOLIII can promote the expression of VEGF. This collagen demonstrated its potential as a raw material for cardiovascular implants.


Asunto(s)
Células Endoteliales , Factor A de Crecimiento Endotelial Vascular , Humanos , Factor A de Crecimiento Endotelial Vascular/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Colágeno Tipo III/metabolismo , Colágeno Tipo III/farmacología , Colágeno/farmacología , Colágeno/metabolismo , Movimiento Celular , Proliferación Celular
4.
ACS Appl Bio Mater ; 6(12): 5252-5263, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37955977

RESUMEN

The surface modification of biologically active factors on tissue-engineering vascular scaffold fails to fulfill the mechanical property and bioactive compounds' sustained release in vivo and results in the inhibition of tissue regeneration of small-diameter vascular grafts in vascular replacement therapies. In this study, biodegradable poly(ε-caprolactone) (PCL) was applied for scaffold preparation, and poly(ethylene glycol) (PG) hydrogel was used to load heparin and hepatocyte growth factor (HGF). In vitro analysis demonstrated that the PCL scaffold could inhibit the heparin release from the PG hydrogel, and the PG hydrogel could inhibit heparin release during the process of PCL degradation. Finally, it results in sustained release of HGF and heparin from the PCL-PG-HGF scaffold. The mechanical property of this hybrid scaffold improved after being coated with the PG hydrogel. In addition, the PCL-PG-HGF scaffold illustrated no inflammatory lesions, organ damage, or biological toxicity in all primary organs, with rapid organization of the endothelial cell layer, smooth muscle regeneration, and extracellular matrix formation. These results indicated that the PCL-PG-HGF scaffold is biocompatible and provides a microenvironment in which a tissue-engineered vascular graft with anticoagulant properties allows regeneration of vascular tissue (Scheme 1). Such findings confirm the feasibility of creating hydrogel scaffolds coated with bioactive factors to prepare novel vascular grafts.


Asunto(s)
Materiales Biocompatibles , Factor de Crecimiento de Hepatocito , Factor de Crecimiento de Hepatocito/farmacología , Preparaciones de Acción Retardada/farmacología , Materiales Biocompatibles/farmacología , Polietilenglicoles/farmacología , Hidrogeles/farmacología , Heparina/farmacología
5.
Int J Biol Macromol ; 251: 126293, 2023 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-37591423

RESUMEN

Cardiovascular disease has become one of the main causes of death. It is the common goal of researchers worldwide to develop small-diameter vascular grafts to meet clinical needs. Collagen is a valuable biomaterial that has been used in the preparation of vascular grafts and has shown good results. Recombinant humanized collagen (RHC) has the advantages of clear chemical structure, batch stability, no virus hazard and low immunogenicity compared with animal-derived collagen, which can be developed as vascular materials. In this study, Poly (l-lactide- ε-caprolactone) with l-lactide/ε-caprolactone (PLCL) and type III recombinant humanized collagen (hCOLIII) were selected as raw materials to prepare vascular grafts, which were prepared by the same-nozzle electrospinning apparatus. Meanwhile, procyanidin (PC), a plant polyphenol, was used to cross-link the vascular grafts. The physicochemical properties and biocompatibility of the fabricated vascular grafts were investigated by comparing with glutaraldehyde (GA) crosslinked vascular grafts and pure PLCL grafts. Finally, the performance of PC cross-linked PLCL-hCOLIII vascular grafts were evaluated by rabbit carotid artery transplantation model. The results indicate that the artificial vascular grafts have good cell compatibility, blood compatibility, and anti-calcification performance, and can remain unobstructed after 30 days carotid artery transplantation in rabbits. The grafts also showed inhibitory effects on the proliferation of SMCs and intimal hyperplasia, demonstrating its excellent performance as small diameter vascular grafts.

6.
Bioengineered ; 13(3): 7925-7938, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-35358008

RESUMEN

A completely confluent endothelial cell (EC) monolayer is required to maintain proper vascular function in small diameter tissue-engineered vascular graft (TEVG). However, the most effective method for EC attachment to the luminal surface and formation of an entire endothelium layer that works in vitro remains a complicated challenge that requires urgent resolution. Although pulsatile flow has been shown to be better suited for the generation of functional endothelium, the optimal frequency setting is unknown. Several pulsatile flow frequencies were used to implant rat bone mesenchymal stem cells (MSC) into the lumen of decellularized porcine carotid arteries. The endothelium's integrity and cell activity were investigated in order to determine the best pulse frequency settings. The results showed that MSC were maximally preserved and exhibited maximal morphological changes with improved endothelialization performance in response to increased pulse stimulation frequency. Increased pulse frequency stimulation stimulates the expression of mechanoreceptor markers, cytoskeleton reorganization in the direction of blood flow, denser skeletal proteins fibronectin, and stronger intercellular connections when compared to constant pulse frequency stimulation. MSC eventually develops an intact endothelial layer with anti-thrombotic properties on the inner wall of the decellularized tubular lumen. Conclusion: The decellularized vessels retain the three-dimensional structure of the vasculature, have a surface topography suitable for MSC growth, and have good mechanical properties. By increasing the frequency of pulsed stimulation, MSC endothelialize the lumen of the decellularized vasculature. It is expected to have anti-thrombotic and anti-neointimal hyperplasia properties after implantation, ultimately improving the patency of TEVG.


Asunto(s)
Prótesis Vascular , Células Madre Mesenquimatosas , Animales , Reactores Biológicos , Células Endoteliales , Ratas , Estrés Mecánico , Porcinos , Ingeniería de Tejidos/métodos , Andamios del Tejido/química
7.
J Biomed Mater Res A ; 109(12): 2493-2505, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34096176

RESUMEN

Long-term in vivo observation in large animal model is critical for evaluating the potential of small diameter tissue engineering vascular graft (SDTEVG) in clinical application, but is rarely reported. In this study, a SDTEVG is fabricated by the electrospinning of poly(ε-caprolactone) and subsequent heparin modification. SDTEVG is implanted into canine's abdominal aorta for 511 days in order to investigate its clinical feasibility. An active and robust remodeling process was characterized by a confluent endothelium, macrophage infiltrate, extracellular matrix deposition and remodeling on the explanted graft. The immunohistochemical and immunofluorescence analysis further exhibit the regeneration of endothelium and smooth muscle layer on tunica intima and tunica media, respectively. Thus, long-term follow-up reveals viable neovessel formation beyond graft degradation. Furthermore, the von Kossa staining exhibits no occurrence of calcification. However, although no TEVG failure or rupture happens during the follow-up, the aneurysm is found by both Doppler ultrasonic and gross observation. Consequently, as-prepared TEVG shows promising potential in vascular tissue engineering if it can be appropriately strengthened to prevent the occurrence of aneurysm.


Asunto(s)
Prótesis Vascular , Vasos Sanguíneos/trasplante , Heparina/química , Poliésteres/química , Aneurisma/prevención & control , Animales , Aorta Abdominal/trasplante , Perros , Endotelio Vascular/crecimiento & desarrollo , Matriz Extracelular/ultraestructura , Humanos , Macrófagos , Músculo Liso Vascular/crecimiento & desarrollo , Proyectos Piloto , Andamios del Tejido , Túnica Íntima , Túnica Media
8.
Mater Sci Eng C Mater Biol Appl ; 116: 111169, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32806292

RESUMEN

In order to accelerate the healing of chronic wound, a hydrogel dressing encapsulating with heparin and basic fibroblast growth factor is prepared by the Michael addition of 4-arm acrylated polyethylene glycol and dithiothreitol. As-prepared hydrogel dressing can combine the advantages of wet healing theory and exogenous growth factor supplement. Furthermore, the encapsulated heparin can play a role in diminishing inflammation and accelerating wound healing in addition to its well-known function of stabilizing basic fibroblast growth factor. In vitro release test shows the hydrogel network is able to sustainably release basic fibroblast growth factor within 10 days by the regulation of heparin, while released growth factor can significantly promote fibroblast's proliferation in vitro. Moreover, the wound healing in rat shows that as-prepared hydrogel dressing could accelerate wound healing in vivo much more effectively compared with blank hydrogel dressing and negative control. Hematoxylin-eosin and Masson's Trichrome staining exhibit the formation of complete and uniform epidermis. Immunohistochemical staining exhibits heparin can help hydrogel dressing to possess low inflammation in early stage, which is beneficial for accelerating wound healing as well as preventing the production of scar tissue. The enzyme-linked immunosorbent assay results demonstrate the exogenous bFGF in hydrogel can significantly upgrade the expressing of vascular endothelial growth factor and transforming growth factor-ß in wound site, which indicate better angiogenesis, and better on-site cell proliferation in wound site, respectively. Those results are further demonstrated by immunohistochemical and immunofluorescence staining. Consequently, as-prepared hydrogel dressing shows promising potential to perform better therapy efficacy in clinic for accelerating wound healing.


Asunto(s)
Heparina , Hidrogeles , Animales , Vendajes , Factor 2 de Crecimiento de Fibroblastos/farmacología , Heparina/farmacología , Hidrogeles/farmacología , Ratas , Factor A de Crecimiento Endotelial Vascular , Cicatrización de Heridas
9.
Soft Matter ; 16(25): 5906-5909, 2020 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-32555865

RESUMEN

Supramolecular hydrogels derived from the self-assembly of α-cyclodextrin with pluronic F127 were found to be built up with polypseudorotaxane nanosheets with a thickness of 30-40 nm and possessed flower-like hierarchically assembled structures. The findings in this work could provide critical guidance for material design for biomedical purposes.

10.
Carbohydr Polym ; 230: 115592, 2020 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-31887923

RESUMEN

The complicated preparation procedure and carrier's suspicious biocompatibility are two major limitations for traditional drug carrier. In this manuscript, a novel polyion complex (PIC) was prepared by simply mixing two biocompatible components, thiolated heparin and doxorubicin (DOX), and subsequently crosslinking under atmosphere, so that it can overcome the above limitations. The PIC's particle size kept stable for one week storage in PBS, and the particles wouldn't decomposed by the dilution, indicating excellent storage and anti-dilution stability resulting from the crosslinking. The PIC can release the larger amount of DOX in acidic environment than psychological environment, and largest amount in acidic and glutathione (GSH) environment, showing the pH and GSH dual sensitive drug release behavior. Furthermore, the PIC exhibited obvious tumor inhibition effect in vivo as well as long circulation ability and low heart toxicity by anti-tumor tests on tumor-bearing mice. Consequently, as-prepared PIC shows promising potential in drug carrier application.


Asunto(s)
Doxorrubicina/farmacología , Liberación de Fármacos , Glutatión/química , Heparina/farmacología , Neoplasias/tratamiento farmacológico , Animales , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/química , Glutatión/genética , Heparina/química , Humanos , Concentración de Iones de Hidrógeno , Ratones , Micelas , Neoplasias/genética , Compuestos de Sulfhidrilo/química
11.
J Phys Chem B ; 123(23): 5004-5013, 2019 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-31117613

RESUMEN

Compared with polypseudorotaxanes (PPRs) formed from the self-assembly of ß-cyclodextrins (ß-CDs) with poly(propylene glycol) (PPG) and γ-CDs with poly( N-isopropylacrylamide) (PNIPAAm), the ratio of the inner cavity size of ß-CD to the cross-sectional area of PNIPAAm appears not appropriate for their self-assembly. For a better understanding of the possibility of ß-CDs including PNIPAAm and the crystal structure of PPRs formed therefrom, the PNIPAAm homo- and copolymers were subjected to self-assembly with ß-CDs in an aqueous solution at room temperature. The results revealed that when ß-CDs meet thicker PNIPAAms, the self-assembly takes place, not only giving rise to PPRs by a manner of main-chain inclusion complexation but also presenting the PPRs a matched over-fit crystal structure different from those of either a matched tight-fit ß-CD-PPG PPR or a mismatched over-fit γ-CD-PNIPAAm PPR. This is most likely due to the thicker PNIPAAm adapting its unfavorable main-chain cross-sectional area to fit into the cavity of ß-CDs by changing the side-chain conformations. Based on the X-ray diffraction patterns, a monoclinic crystal system was created from these PPRs and the unit cell parameters calculated were as follows: a = 15.3 Å, b = 10.3 Å, and c = 21.2 Å; ß = 110.3°; and space group P2. It suggested that this matched over-fit crystal structure would possess a Mosaic crystal structure rather than a typical channel-like one.

12.
Carbohydr Polym ; 211: 370-379, 2019 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-30824101

RESUMEN

Heparin as negative polysaccharide is a universal building block to form polyion complex with different cationic counterparts. In this paper, three different cations, including chitosan, benzyldodecyldimethyl ammonium bromide and doxorubicin hydrochloride, were used to prepare heparin-based polyion complexes (HPICs). Their morphologies could be tuned by heparin content in HPIC, and they also showed pH-sensitive decomposition. Doxorubicin was further encapsulated into micelle and vesicle carrier made from heparin-benzyldodecyl dimethyl ammonium bromide PIC, whereas heparin-doxorubicin PIC could be directly used as drug carrier. In vitro drug release proved the drug carriers exhibit obvious pH sensitive release behaviour. Cytotoxicity indicated the drug carrier possessed significant cytotoxicity to tumor cells. The cell uptake observed by CLSM showed the carrier was able to deliver antitumor drug into tumor cell's nucleus. Consequently, these results showed the promising potential of HPIC in drug carrier application.


Asunto(s)
Portadores de Fármacos , Heparina , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/química , Compuestos de Benzalconio/administración & dosificación , Compuestos de Benzalconio/química , Transporte Biológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Quitosano/administración & dosificación , Quitosano/química , Doxorrubicina/administración & dosificación , Doxorrubicina/química , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Liberación de Fármacos , Heparina/administración & dosificación , Heparina/química , Humanos , Concentración de Iones de Hidrógeno , Micelas
13.
Langmuir ; 34(46): 14076-14084, 2018 11 20.
Artículo en Inglés | MEDLINE | ID: mdl-30372624

RESUMEN

A syndiotactic-rich PHEMA oligomer ( rr = 74%, DP = 29, PDI = 1.19) was synthesized and subsequently subjected to self-assembly with a varying amount of γ-CDs in its aqueous solution to create mismatched overfit polypseudorotaxanes (PPRs). The inclusion complexation proceeded in an obvious mismatched manner between the cavity of γ-CDs and the cross-sectional area of an incoming PHEMA chain. The 2D-NOESY NMR analysis provided direct evidence indicating that two adjacent pendant hydroxyethyl groups in PHEMA preferably adopt a curled conformation to pass through the cavity of γ-CDs, giving the PPRs characteristics of a mismatched overfit instead of a matched tight-fit crystal structure. The results suggested that the mutual adaption of pendant side chains of HEMA units with the cavity geometry of γ-CDs would play a dominant role in this unfavorable overfit inclusion complexation besides the size of γ-CDs and the stereoregularity of the PHEMA chain.

14.
Carbohydr Polym ; 140: 260-8, 2016 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-26876853

RESUMEN

Heparin based polymer drug which could self-assemble into sphere micelle in water was firstly prepared by grafting paclitaxel (PTX) into the hydroxyl of heparin via aconitic bond as pH sensitive spacer. Positive charged drug DOX·HCl and cationic folic acid (CFA) can be further loaded into the polymer drug via electrostatic interaction in aqueous solution so as to prepare smart drug carrier. The drug carrier was able to release more PTX and DOX at pH 4.8 than that at pH 7.4, exhibiting pH sensitivity for two drugs. Furthermore, tumor cell cytotoxicity test proved it possessed significant cytotoxicity against tumor cells MDA-MB-231 as well as its active tumor targeting ability resulting from the loading of CFA. Cellular uptake and intracellular distribution were further revealed by confocal laser scanning microscopy (CLSM). In conclusion, this paper not only provided a simple strategy but also indicated heparin is a versatile platform for the design of smart drug carrier. The as-prepared drug carrier also showed promising potential in chemotherapy.


Asunto(s)
Portadores de Fármacos/química , Portadores de Fármacos/síntesis química , Heparina/química , Heparina/síntesis química , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/farmacología , Transporte Biológico , Línea Celular Tumoral , Técnicas de Química Sintética , Liberación de Fármacos , Ácido Fólico/química , Humanos , Paclitaxel/química , Paclitaxel/metabolismo , Paclitaxel/farmacología
15.
Beilstein J Org Chem ; 10: 2461-9, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25383117

RESUMEN

A pentablock copolymer was prepared via the atom transfer radical polymerization of 2-hydroxyethyl methacrylate (HEMA) initiated by 2-bromoisobutyryl end-capped PPO-PEO-PPO as a macroinitiator in DMF. Attaching PHEMA blocks altered the self-assembly process of the pentablock copolymer with γ-CDs in aqueous solution. Before attaching the PHEMA, the macroinitiator was preferentially bent to pass through the inner cavity of γ-CDs to give rise to tight-fit double-chain stranded polypseudorotaxanes (PPRs). After attaching the PHEMA, the resulting pentablock copolymer was single-chain stranded into the interior of γ-CDs to form more stable, loose-fit PPRs. The results of (1)H NMR, WXRD, DSC, TGA, (13)C CP/MAS NMR and FTIR analyses indicated that γ-CDs can accommodate and slip over PHEMA blocks to randomly distribute along the entire pentablock copolymer chain. This results in unique, single-chain stranded PPRs showing no characteristic channel-type crystal structure.

16.
J Biomed Mater Res A ; 102(3): 880-9, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-23554308

RESUMEN

PCL-heparin conjugates were synthesized by coupling mono-hydroxyl terminated PCL (Mn = 2000-10000 g/mol) with heparin via EDC/NHS chemistry. The conjugates enabled to self-assemble into the core-shell nanoparticles in around 100 nm diameter to load binary anti-cancer drugs. Lipophilic and neutral paclitaxel (PTX) was first encapsulated in the core, and then hydrophilic and positive charged doxorubicin (DOX) was incorporated into the negative charged shell of PTX loaded nanoparticles via the electrostatic interaction. The in vitro release profiles of the binary-drug loaded nanoparticles revealed that both PTX and DOX were sustainably released from the particles but behaved differently. The release of DOX was pH dependent, ensuring more drug to be released in the tumor cells than in the normal ones. Hence these particles were featured by a sequential controlled drug delivery behavior with a significant cytotoxicity to cervical cancer (Hela cell) and breast cancer (MDA-MB-321) cells. The CLSM observations clearly indicated that both loaded PTX and DOX aggregated in the nucleus of tumor cells to exert their anti-tumor pharmacodynamic effect on the cells.


Asunto(s)
Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada/química , Doxorrubicina/administración & dosificación , Heparina/química , Paclitaxel/administración & dosificación , Poliésteres/química , Antineoplásicos/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/farmacología , Femenino , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Paclitaxel/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico
17.
Biomater Sci ; 1(12): 1282-1291, 2013 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-32481983

RESUMEN

A pH-sensitive nano antitumor drug delivery system was prepared by conjugating doxorubicin (DOX) to amphiphilic polyrotaxane (PR)-based block copolymers through a pH-sensitive cis-aconityl moiety. The resulting polymer-drug conjugates were able to self-assemble into polymeric micelles in an aqueous solution with diameters varying from 297 nm to 178 nm after the conjugation as evidenced by DLS measurements. The pH-sensitive cis-aconityl linkage provided a controlled and sustained release of DOX over a period of more than 5 days in an acidic environment mimicking the tumor microenvironment, and a negligible amount of release in an environment with physiological pH. The nanoparticles had lower cytotoxicity than the free drug and can efficiently transfer and release the drug into HeLa cells. With these promising properties, the PR-based block copolymers have the potential to be carriers for the controlled release of antitumor drugs.

18.
J Biomed Mater Res A ; 100(12): 3251-8, 2012 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22733560

RESUMEN

Poly(ε-caprolactone) (PCL) was conjugated with heparin and fabricated into nonwoven tubular scaffold by electrospinning. The dynamic contact angle analysis revealed the hydrophilicity improvement due to heparin concentrating on the conjugate surface. The microbicinchoninic acid and quartz crystal microbalance measurements implied that the conjugate can significantly reduce the absorption of plasma protein, such as albumin and fibrinogen, indicative of the good blood biocompatibility. As evidenced by Enzyme Linked Immunosorbent Assay, the electrospun conjugate scaffolds possessed a higher loading capability of vascular endothelial growth factor (VEGF) than that of the blank PCL in aqueous solution via static interaction. The viability of loaded VEGF was evaluated by cell culture and adhesion tests. The amount and morphology of cells were substantially improved after VEGF was loaded into scaffolds exhibiting excellent cell biocompatibility. To assess the in vivo biocompatibility, a tubular scaffold (L = 4 cm, D = 2 mm) was transplanted into dog's femoral artery. The scaffold patency was inspected by carotid artery angiography 4 weeks after implantation. The explanted scaffold was also investigated by histological analysis including hematoxyline eosin, Millere Masson (collagen and elastin), and von Kossa (calcium) stain. Furthermore, von Willebrand factor immunohistochemical stain was performed to examine the formation of endothelial layer. The conjugate shows the potential to be used as scaffold materials in vascular tissue engineering.


Asunto(s)
Materiales Biocompatibles/farmacología , Vasos Sanguíneos/efectos de los fármacos , Heparina/farmacología , Ensayo de Materiales/métodos , Poliésteres/farmacología , Ingeniería de Tejidos/métodos , Andamios del Tejido/química , Adsorción , Angiografía , Animales , Células Cultivadas , Perros , Células Endoteliales/citología , Células Endoteliales/efectos de los fármacos , Células Endoteliales/ultraestructura , Heparina/química , Humanos , Inmunohistoquímica , Masculino , Poliésteres/química , Coloración y Etiquetado , Factor A de Crecimiento Endotelial Vascular/farmacología
19.
Macromol Rapid Commun ; 33(13): 1143-8, 2012 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-22492506

RESUMEN

A polypseudorotaxane (PPR) comprising γ-cyclodextrin (γ-CD) as host molecules and poly(N-isopropylacrylamide) (PNIPAM) as a guest polymer is prepared via self-assembly in aqueous solution. Due to the bulky pendant isopropylamide group, PNIPAM exhibits size-selectivity toward self-assembly with α-, ß-, and γ-CDs. It can fit into the cavity of γ-CD to give rise to a PPR, but cannot pass through α-CD and ß-CD under the same conditions. The ratio of the number of γ-CD molecules to entrapped NIPAM repeat units is kept at 1:2.2 or 1:2.4, determined by (1) H NMR spectroscopy and TGA analysis, respectively, indicating that there are more than 2 but less than 3 NIPAM repeat units included by one γ-CD molecule. This finding opens new avenues to PPR-based supramolecular polymers to be used as solid, stimuli-responsive materials.


Asunto(s)
Acrilamidas/química , Polímeros/síntesis química , Rotaxanos/química , gamma-Ciclodextrinas/química , Resinas Acrílicas , Estructura Molecular , Polimerizacion , Polímeros/química , beta-Ciclodextrinas/química
20.
Artículo en Chino | MEDLINE | ID: mdl-20839451

RESUMEN

OBJECTIVE: To explore the method of preparing the electrospinning of synthesized triblock copolymers of epsilon-caprolactone and L-lactide (PCLA) for the biodegradable vascular tissue engineering scaffold and to investigate its biocompatibility in vitro. METHODS: The biodegradable vascular tissue engineering scaffold was made by the electrospinning process of PCLA. A series of biocompatibility tests were performed. Cytotoxicity test: the L929 cells were cultured in 96-well flat-bottomed plates with extraction media of PCLA in the experimental group and with the complete DMEM in control group, and MTT method was used to detect absorbance (A) value (570 nm) every day after culture. Acute general toxicity test: the extraction media and saline were injected into the mice's abdominal cavity of experimental and control groups, respectively, and the toxicity effects on the mice were observed within 72 hours. Hemolysis test: anticoagulated blood of rabbit was added into the extracting solution, saline, and distilled water in 3 groups, and MTT method was used to detect A value in 3 groups. Cell attachment test: the L929 cells were seeded on the PCLA material and scanning electron microscope (SEM) observation was performed 4 hours and 3 days after culture. Subcutaneous implantation test: the PCLA material was implanted subcutaneously in rats and the histology observation was performed at 1 and 8 weeks. RESULTS: Scaffolds had the characteristics of white color, uniform texture, good elasticity, and tenacity. The SEM showed that the PCLA ultrafine fibers had a smooth surface and proper porosity; the fiber diameter was 1-5 microm and the pore diameter was in the range of 10-30 microm. MTT detection suggested that there was no significant difference in A value among 3 groups every day after culturing (P > 0.05). The mice in 2 groups were in good physical condition and had no respiratory depression, paralysis, convulsion, and death. The hemolysis rate was 1.18% and was lower than the normal level (5%). The SEM showed a large number of attached L929 cells were visible on the surface of the PCLA material at 4 hours after implantation and the cells grew well after 3 days. The PCLA material was infiltrated by the inflammatory cells after 1 week. The inflammatory cells reduced significantly and the fiber began abruption after 8 weeks. CONCLUSION: The biodegradable vascular tissue engineering scaffold material made by the electrospinning process of PCLA has good microstructure without cytotoxicity and has good biocompatibility. It can be used as an ideal scaffold for vascular tissue engineering.


Asunto(s)
Materiales Biocompatibles , Ensayo de Materiales , Poliésteres , Andamios del Tejido , Animales , Vasos Sanguíneos , Línea Celular , Femenino , Masculino , Ratones , Ratones Endogámicos ICR , Conejos , Ratas , Ratas Sprague-Dawley , Ingeniería de Tejidos/métodos
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