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Antitumoral activity of L-ascorbic acid-poly-D,L-(lactide-co-glycolide) nanoparticles containing violacein
Dorival Martins, Lucas Frungillo, Maristela C Anazzetti, et al
International Journal of Nanomedicine , 2010, DOI: http://dx.doi.org/10.2147/IJN.S7833
Abstract: ntitumoral activity of L-ascorbic acid-poly-D,L-(lactide-co-glycolide) nanoparticles containing violacein Original Research (5080) Total Article Views Authors: Dorival Martins, Lucas Frungillo, Maristela C Anazzetti, et al Published Date January 2010 Volume 2010:5 Pages 77 - 85 DOI: http://dx.doi.org/10.2147/IJN.S7833 Dorival Martins1, Lucas Frungillo2, Maristela C Anazzetti2, Patrícia S Melo3, Nelson Durán1 1Institute of Chemistry, Biological Chemistry Laboratory, Universidade Estadual de Campinas-UNICAMP, C.P. 6154, CE P 13083-970, Campinas, SP, Brazil; 2Institute of Biology, Cell Cultures and Biopharmaceutical Laboratory, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil; 3Campinas Integrated Metropolitan Faculties-METROCAMP, Campinas, SP, Brazil Abstract: It has been demonstrated that tumoral cells have a higher uptake of ascorbic acid compared to normal cells. This differential characteristic can be used as a way to improve the specificity of antitumoral compounds if combined with polymeric drug delivery systems. The aim of this study was to prepare, characterize and evaluate the antitumoral activity of poly-D,L-(lactide-co-glycolide) 50:50 loading the antitumoral compound violacein and capped with L-ascorbic acid. Nanoparticles were prepared using the nanoprecipitation method and morphologically characterized by scanning electron microscopy (SEM). The average diameter and Zeta potential were determined by photon correlation spectroscopy method (PCS), and assays were carried out to determine the content of ascorbic acid and in vitro drug release kinetics. The antitumoral activity of this system was also evaluated against HL-60 cells by tetrazolium reduction assay. Nanoparticles with size distribution between 300–400 nm and strong negative outer surface (-40 mV) were obtained by this method. Analysis of ascorbic acid content showed that this compound was mainly localized on the external surface of nanoparticles. Violacein loading efficiency was determined as 32% ± 1% and this drug was gradually released from nanoparticles at different rates depending on the composition of the release media. In addition, this system was observed to be 2 × more efficient as an antitumoral compared with free violacein.
Antitumoral activity of L-ascorbic acid-poly-D,L-(lactide-co-glycolide) nanoparticles containing violacein  [cached]
Dorival Martins,Lucas Frungillo,Maristela C Anazzetti,et al
International Journal of Nanomedicine , 2010,
Abstract: Dorival Martins1, Lucas Frungillo2, Maristela C Anazzetti2, Patrícia S Melo3, Nelson Durán11Institute of Chemistry, Biological Chemistry Laboratory, Universidade Estadual de Campinas-UNICAMP, C.P. 6154, CE P 13083-970, Campinas, SP, Brazil; 2Institute of Biology, Cell Cultures and Biopharmaceutical Laboratory, Universidade Estadual de Campinas, UNICAMP, Campinas, SP, Brazil; 3Campinas Integrated Metropolitan Faculties-METROCAMP, Campinas, SP, BrazilAbstract: It has been demonstrated that tumoral cells have a higher uptake of ascorbic acid compared to normal cells. This differential characteristic can be used as a way to improve the specificity of antitumoral compounds if combined with polymeric drug delivery systems. The aim of this study was to prepare, characterize and evaluate the antitumoral activity of poly-D,L-(lactide-co-glycolide) 50:50 loading the antitumoral compound violacein and capped with L-ascorbic acid. Nanoparticles were prepared using the nanoprecipitation method and morphologically characterized by scanning electron microscopy (SEM). The average diameter and Zeta potential were determined by photon correlation spectroscopy method (PCS), and assays were carried out to determine the content of ascorbic acid and in vitro drug release kinetics. The antitumoral activity of this system was also evaluated against HL-60 cells by tetrazolium reduction assay. Nanoparticles with size distribution between 300–400 nm and strong negative outer surface (-40 mV) were obtained by this method. Analysis of ascorbic acid content showed that this compound was mainly localized on the external surface of nanoparticles. Violacein loading efficiency was determined as 32% ± 1% and this drug was gradually released from nanoparticles at different rates depending on the composition of the release media. In addition, this system was observed to be 2 × more efficient as an antitumoral compared with free violacein.Keywords: violacein, ascorbic acid, nanoparticles, PLGA
Physicochemical stability of poly(lactide-co-glycolide) nanocapsules containing the local anesthetic Bupivacaine
Moraes, Carolina M.;Paula, Eneida de;Rosa, André H.;Fraceto, Leonardo F.;
Journal of the Brazilian Chemical Society , 2010, DOI: 10.1590/S0103-50532010000600008
Abstract: this paper describes the preparation of poly(dl-lactide-co-glicolide) (plga) nanocapsules as a drug carrier system for the local anesthetic bupivacaine. the system was characterized and its stability investigated. the results showed a size distribution with a polydispersity index of 0.12, an average diameter of 148 nm, a zeta potential of -43.5 mv and an entrapment efficiency of 75.8%. the physicochemical properties of polymeric nanocapsule suspensions (average diameter, polydispersity, zeta potential and drug association efficiency) were evaluated as a function of time to determine the formulation stability. the formulation did not display major changes in these properties over the time, and it was considered stable up to 120 days of storage at room temperature. the results reported here which refer to the initial characterization of these new formulations for the local anesthetic bupivacaine show a promising potential for future in vivo studies.
Synthesis and Physicochemical Characterization of Biodegradable Star-Shaped Poly Lactide-Co-Glycolide-β-Cyclodextrin Copolymer Nanoparticles Containing Albumin  [PDF]
Soodabeh Davaran, Akbar Rezaei, Somayeh Alimohammadi, Amir Ahmad Khandaghi, Kazem Nejati-Koshki, Hamid Tayefi Nasrabadi, Abolfazl Akbarzadeh
Advances in Nanoparticles (ANP) , 2014, DOI: 10.4236/anp.2014.31003
Abstract:

The purposes of this research were to synthesize and characterize star-shaped poly lactide-co-glycolide-β-cyclo-dextrin (PLGA-β-CD) copolymer by reacting L-lactide, glycolide and β-cyclodextrin in the presence of stannous octoate as a catalyst. The structure of PLGA-β-CD copolymer was confirmed with 1H-NMR, 13C-NMR and FT-IR spectra. Albumin as a model peptide drug was encapsulated within nanoparticles made of PLGA-β-CD with a modified double emulsion method. Transmission electron microscopy (TEM) and scanning electron microscopy (SEM) photomicrographs showed that the nanoparticles have the mean diameter within the range of 80 - 210 nm. Also they were almost spherical in shape. Effects of the experimental parameters, such as copolymer composition, copolymer concentration, and reaction temperature, on particular size and encapsulation efficiency were investigated.

Nanoparticles of Poly(Lactide-Co-Glycolide)-d-a-Tocopheryl Polyethylene Glycol 1000 Succinate Random Copolymer for Cancer Treatment  [cached]
Ma Yuandong,Zheng Yi,Liu Kexin,Tian Ge
Nanoscale Research Letters , 2010,
Abstract: Cancer is the leading cause of death worldwide. Nanomaterials and nanotechnologies could provide potential solutions. In this research, a novel biodegradable poly(lactide-co-glycolide)-d-a-tocopheryl polyethylene glycol 1000 succinate (PLGA-TPGS) random copolymer was synthesized from lactide, glycolide and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS) by ring-opening polymerization using stannous octoate as catalyst. The obtained random copolymers were characterized by 1H NMR, FTIR, GPC and TGA. The docetaxel-loaded nanoparticles made of PLGA-TPGS copolymer were prepared by a modified solvent extraction/evaporation method. The nanoparticles were then characterized by various state-of-the-art techniques. The results revealed that the size of PLGA-TPGS nanoparticles was around 250 nm. The docetaxel-loaded PLGA-TPGS nanoparticles could achieve much faster drug release in comparison with PLGA nanoparticles. In vitro cellular uptakes of such nanoparticles were investigated by CLSM, demonstrating the fluorescence PLGA-TPGS nanoparticles could be internalized by human cervix carcinoma cells (HeLa). The results also indicated that PLGA-TPGS-based nanoparticles were biocompatible, and the docetaxel-loaded PLGA-TPGS nanoparticles had significant cytotoxicity against Hela cells. The cytotoxicity against HeLa cells for PLGA-TPGS nanoparticles was in time- and concentration-dependent manner. In conclusion, PLGA-TPGS random copolymer could be acted as a novel and promising biocompatible polymeric matrix material applicable to nanoparticle-based drug delivery system for cancer chemotherapy.
Nanofibrous poly(lactide-co-glycolide) membranes loaded with diamond nanoparticles as promising substrates for bone tissue engineering
Parizek M, Douglas TEL, Novotna K, Kromka A, Brady MA, Renzing A, Voss E, Jarosova M, Palatinus L, Tesarek P, Ryparova P, Lisa V, dos Santos AM, Bacakova L
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S26665
Abstract: nofibrous poly(lactide-co-glycolide) membranes loaded with diamond nanoparticles as promising substrates for bone tissue engineering Original Research (7037) Total Article Views Authors: Parizek M, Douglas TEL, Novotna K, Kromka A, Brady MA, Renzing A, Voss E, Jarosova M, Palatinus L, Tesarek P, Ryparova P, Lisa V, dos Santos AM, Bacakova L Video presented by Lucie Bacakova. Views: 234 Published Date April 2012 Volume 2012:7 Pages 1931 - 1951 DOI: http://dx.doi.org/10.2147/IJN.S26665 Received: 01 October 2011 Accepted: 17 December 2011 Published: 18 April 2012 Martin Parizek1, Timothy EL Douglas2, Katarina Novotna1, Alexander Kromka3, Mariea A Brady4, Andrea Renzing4, Eske Voss4, Marketa Jarosova3, Lukas Palatinus3, Pavel Tesarek5, Pavla Ryparova5, Vera Lisa1, Ana M dos Santos2, Lucie Bacakova1 1Department of Biomaterials and Tissue Engineering, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 2Polymer Chemistry and Biomaterials Group, Ghent University, Ghent, Belgium; 3Institute of Physics, Academy of Sciences of the Czech Republic, Prague, Czech Republic; 4Department of Oral and Maxillofacial Surgery, University of Kiel, Kiel, Germany; 5Czech Technical University in Prague, Faculty of Civil Engineering, Prague, Czech Republic Background: Nanofibrous scaffolds loaded with bioactive nanoparticles are promising materials for bone tissue engineering. Methods: In this study, composite nanofibrous membranes containing a copolymer of L-lactide and glycolide (PLGA) and diamond nanoparticles were fabricated by an electrospinning technique. PLGA was dissolved in a mixture of methylene chloride and dimethyl formamide (2:3) at a concentration of 2.3 wt%, and nanodiamond (ND) powder was added at a concentration of 0.7 wt% (about 23 wt% in dry PLGA). Results: In the composite scaffolds, the ND particles were either arranged like beads in the central part of the fibers or formed clusters protruding from the fibers. In the PLGA-ND membranes, the fibers were thicker (diameter 270 ± 9 nm) than in pure PLGA meshes (diameter 218 ± 4 nm), but the areas of pores among these fibers were smaller than in pure PLGA samples (0.46 ± 0.02 μm2 versus 1.28 ± 0.09 μm2 in pure PLGA samples). The PLGA-ND membranes showed higher mechanical resistance, as demonstrated by rupture tests of load and deflection of rupture probe at failure. Both types of membranes enabled the attachment, spreading, and subsequent proliferation of human osteoblast-like MG-63 cells to a similar extent, although these values were usually lower than on polystyrene dishes. Nevertheless, the cells on both types of membranes were polygonal or spindle-like in shape, and were distributed homogeneously on the samples. From days 1–7 after seeding, their number rose continuously, and at the end of the experiment, these cells were able to create a confluent layer. At the same time, the cell viability, evaluated by a LIVE/DEAD viability/cytotoxicity kit, ranged from 92% to
ROS-inducing potential, influence of different porogens and in vitro degradation of poly (D,L-lactide-co-glycolide)-based material
eXPRESS Polymer Letters , 2011, DOI: 10.3144/expresspolymlett.2011.97
Abstract: Porous, poly(D,L-lactide-co-glycolide) (PLGA) materials were prepared by physicochemical solvent/non-solvent method with polyvinyl pyrrolidone (PVP) as a stabilizer and with silicone oil, paraffin, hydrogen peroxide or sodium chloride as a porogen. The obtained PLGA particles without porogens are non-agglomerated, uniform and with particle size on the submicron scale. The formation of intracellular reactive oxygen species (ROS) was measured spectrophotometrically using a fluorescent probe, 2,7-dichlorofluorescein diacetate (DCFH-DA) and it is shown that PLGA nanospheres are not inducers of intracellular formation. Porous PLGA scaffolds obtained in the experiment with sodium chloride as porogen and water as solvent of the porogen had apparently uniform pore morphology with spheroidal pore in shape and well controlled three-dimensional interconnected network. PLGA scaffolds are highly porous with similar porosity values. The degradation of PLGA nanoparticles and PLGA porous materials were studied in phosphate buffered saline as a degradation medium. The samples were characterized by Infrared Spectroscopy (IR), X-ray difractometry, Zeta potential measurements, Scanning Electron Microscopy (SEM) and Ultraviolet Spectroscopy (UV).
Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4
Wang M, Zhang Y, Feng J, Gu T, Dong Q, Yang X, Sun Y, Wu Y, Chen Y, Kong W
International Journal of Nanomedicine , 2013, DOI: http://dx.doi.org/10.2147/IJN.S41457
Abstract: eparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4 Original Research (142) Total Article Views Authors: Wang M, Zhang Y, Feng J, Gu T, Dong Q, Yang X, Sun Y, Wu Y, Chen Y, Kong W Published Date March 2013 Volume 2013:8 Pages 1141 - 1154 DOI: http://dx.doi.org/10.2147/IJN.S41457 Received: 11 December 2012 Accepted: 29 January 2013 Published: 20 March 2013 Mengshu Wang,1* Yong Zhang,1* Jiao Feng,1 Tiejun Gu,1 Qingguang Dong,1 Xu Yang,2 Yanan Sun,1 Yongge Wu,1 Yan Chen,1 Wei Kong1 1National Engineering Laboratory for AIDS Vaccine, College of Life Science, Jilin University, Changchun, People’s Republic of China; 2BCHT Biopharm Co, Ltd, Changchun, People’s Republic of China *These authors contributed equally to this work Background: Exendin-4 is an incretin mimetic agent approved for type 2 diabetes treatment. However, the required frequent injections restrict its clinical application. Here, the potential use of chitosan-coated poly (d,l-lactide-co-glycolide) (CS-PLGA) nanoparticles was investigated for intestinal delivery of exendin-4. Methods and results: Nanoparticles were prepared using a modified water–oil–water (w/o/w) emulsion solvent-evaporation method, followed by coating with chitosan. The physical properties, particle size, and cell toxicity of the nanoparticles were examined. The cellular uptake mechanism and transmembrane permeability were performed in Madin-Darby canine kidney-cell monolayers. Furthermore, in vivo intraduodenal administration of exendin-4-loaded nanoparticles was carried out in rats. The PLGA nanoparticle coating with chitosan led to a significant change in zeta potential, from negative to positive, accompanied by an increase in particle size of ~30 nm. Increases in both the molecular weight and degree of deacetylation of chitosan resulted in an observable increase in zeta potential but no apparent change in the particle size of ~300 nm. Both unmodified PLGA and chitosan-coated nanoparticles showed only slight cytotoxicity. Use of different temperatures and energy depletion suggested that the cellular uptake of both types of nanoparticles was energy-dependent. Further investigation revealed that the uptake of PLGA nanoparticles occurred via caveolin-mediated endocytosis and that of CS-PLGA nanoparticles involved both macropinocytosis and clathrin-mediated endocytosis, as evidenced by using endocytic inhibitors. However, under all conditions, CS-PLGA nanoparticles showed a greater potential to be transported into cells, as shown by flow cytometry and confocal microscopy. Transmembrane permeability analysis showed that unmodified and modified PLGA nanoparticles could improve the transport of exendin-4 by up to 8.9- and 16.5-fold, respectively, consistent with the evaluation in rats. Conclusion: The chitosan-coated nanoparticles have a higher transport potential over both free drug and unmodified particles,
Development of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol
Sanna V, Roggio AM, Siliani S, Piccinini M, Marceddu S, Mariani A, Sechi M
International Journal of Nanomedicine , 2012, DOI: http://dx.doi.org/10.2147/IJN.S36684
Abstract: pment of novel cationic chitosan- and anionic alginate–coated poly(D,L-lactide-co-glycolide) nanoparticles for controlled release and light protection of resveratrol Original Research (2155) Total Article Views Authors: Sanna V, Roggio AM, Siliani S, Piccinini M, Marceddu S, Mariani A, Sechi M Published Date October 2012 Volume 2012:7 Pages 5501 - 5516 DOI: http://dx.doi.org/10.2147/IJN.S36684 Received: 07 August 2012 Accepted: 12 September 2012 Published: 17 October 2012 Vanna Sanna,1 Anna Maria Roggio,1 Silvia Siliani,1 Massimo Piccinini,1 Salvatore Marceddu,2 Alberto Mariani,3 Mario Sechi3 1Porto Conte Ricerche, Alghero, Italy; 2Istituto di Scienze delle Produzioni Alimentari (ISPA), Consiglio Nazionale delle Ricerche (CNR), Sezione di Sassari, Italy; 3Department of Chemistry and Pharmacy, University of Sassari, Sassari, Italy Background: Resveratrol, like other natural polyphenols, is an extremely photosensitive compound with low chemical stability, which limits the therapeutic application of its beneficial effects. The development of innovative formulation strategies, able to overcome physicochemical and pharmacokinetic limitations of this compound, may be achieved via suitable carriers able to associate controlled release and protection. In this context, nanotechnology is proving to be a powerful strategy. In this study, we developed novel cationic chitosan (CS)- and anionic alginate (Alg)-coated poly(d,l-lactide-co-glycolide) nanoparticles (NPs) loaded with the bioactive polyphenolic trans-(E)-resveratrol (RSV) for biomedical applications. Methods: NPs were prepared by the nanoprecipitation method and characterized in terms of morphology, size and zeta potential, encapsulation efficiency, Raman spectroscopy, swelling properties, differential scanning calorimetry, and in vitro release studies. The protective effect of the nanosystems under the light-stressed RSV and long-term stability were investigated. Results: NPs turned out to be spherical in shape, with size ranging from 135 to about 580 nm, depending on the composition and the amount of polyelectrolytes, while the encapsulation efficiencies increased from 8% of uncoated poly(d,l-lactide-co-glycolide) (PLGA) to 23% and 32% of Alg- and CS-coated PLGA NPs, respectively. All nanocarriers are characterized by a biphasic release pattern, and more effective controlled release rates are obtained for NPs formulated with higher polyelectrolyte concentrations. Stability studies revealed that encapsulation provides significant protection against light-exposure degradation, by reducing the trans–cis photoisomerization reaction. Moreover, the nanosystems are able to prevent the degradation of trans isoform and the leakage of RSV from the carrier for a period of 6 months. Conclusion: Our findings indicated that the newly developed CS- and Alg-coated PLGA NPs are suitable to be used for the delivery of bioactive RSV. The encapsulation of RSV into optimized polymeric NPs provides improved drug loading
Synthesis and Characterization of Poly(D,L-Lactide-co-Glycolide) Copolymer  [PDF]
Cynthia D’Avila Carvalho Erbetta, Ricardo José Alves, Jarbas Magalh?es Resende, Roberto Fernando de Souza Freitas, Ricardo Geraldo de Sousa
Journal of Biomaterials and Nanobiotechnology (JBNB) , 2012, DOI: 10.4236/jbnb.2012.32027
Abstract: The copolymer poly(D,L-lactide-co-glycolide) is one of the most interesting polymers for medical applications. This interest is justified by the fact that it is bioreabsorbable, biocompatible and non-toxic, while its degradation kinetics can be modified by the copolymerization ratio of the monomers. In this study, copolymers were synthesised at 175?C by opening the rings of the cyclic dimers of the D,L-lactide and glycolide monomers in the presence of stannous octoate initiator and lauryl alcohol co-initiator. The application of vacuum to the reaction medium, coupled with adequate stirring, is essential for obtaining good results. The following analytical techniques were used to characterise the synthesised copolymers: Differential Scanning Calorimetry (DSC), Thermogravimetry (TG), Nuclear Magnetic Resonance Spectroscopy (NMR) and Fourier Transform Infrared Spectroscopy (FTIR). Both the input monomers and the reaction products were analysed. Important characteristics, such as melting temperature, glass transition temperature, thermal stability, chemical composition and the ratio of the monomers in the synthesised copolymer, were obtained from these analyses. These results helped to infer the absence of residual monomers in the synthesised copolymers.
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