The t-PA-encapsulated PLGA nanoparticles shelled with CS or CS-GRGD alter both permeation through and dissolving patterns of blood clots compared with t-PA solution: An in vitro thrombolysis study
Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t‐PA) encapsula...
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| Published in | Journal of biomedical materials research. Part A Vol. 91A; no. 3; pp. 753 - 761 |
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| Abstract | Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t‐PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS‐GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t‐PA encapsulated in NPs. The t‐PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS‐GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t‐PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS‐GRGD NPs revealed extremely rough surfaces to a depth of 100 μm, indicating that a cross‐permeation direction of clot lysis occurred, while those dissolved with t‐PA solution showed slightly rough surfaces to a depth of 12 μm. Permeation through and clot dissolution patterns of thrombolysis with t‐PA encapsulated in NPs shelled with CS or CS‐GRGD distinctly differed from those dissolved with t‐PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009 |
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| AbstractList | Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 [micro]m, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 [micro]m. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t‐PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS‐GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t‐PA encapsulated in NPs. The t‐PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS‐GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t‐PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS‐GRGD NPs revealed extremely rough surfaces to a depth of 100 μm, indicating that a cross‐permeation direction of clot lysis occurred, while those dissolved with t‐PA solution showed slightly rough surfaces to a depth of 12 μm. Permeation through and clot dissolution patterns of thrombolysis with t‐PA encapsulated in NPs shelled with CS or CS‐GRGD distinctly differed from those dissolved with t‐PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009 Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 mum, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 mum. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis.Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 mum, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 mum. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t‐PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS‐GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t‐PA encapsulated in NPs. The t‐PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS‐GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t‐PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS‐GRGD NPs revealed extremely rough surfaces to a depth of 100 μm, indicating that a cross‐permeation direction of clot lysis occurred, while those dissolved with t‐PA solution showed slightly rough surfaces to a depth of 12 μm. Permeation through and clot dissolution patterns of thrombolysis with t‐PA encapsulated in NPs shelled with CS or CS‐GRGD distinctly differed from those dissolved with t‐PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. © 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009 Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 Delta *mm, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 Delta *mm. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. [copy 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009 Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs) encapsulated liposomes or PEG microparticles. Recent reports have also described acceleration of thrombolysis using tissue type PA (t-PA) encapsulated in PLGA nanoparticles (NPs) coated with chitosan (CS) or CS-GRGD by interactions between the NPs and blood clots. However, the permeation through and dissolving patterns in thrombolysis with the aforementioned microparticles or NPs, which may be clinically relevant to the recovery status of the posttreatments, have not been reported. Therefore, this work studied such phenomena in thrombolysis with t-PA encapsulated in NPs. The t-PA solution and the NPs exhibited distinctly different permeation patterns of dissolved clots. Plasma permeates through clots showed a stream flow or burst flow phenomena when lyzed with NPs shelled with CS or CS-GRGD, respectively, whereas a diffusion pattern was observed in those lyzed with t-PA solution. At the outlet position of clots, the clots dissolved with PLGA/CS and PLGA/CS-GRGD NPs revealed extremely rough surfaces to a depth of 100 mum, indicating that a cross-permeation direction of clot lysis occurred, while those dissolved with t-PA solution showed slightly rough surfaces to a depth of 12 mum. Permeation through and clot dissolution patterns of thrombolysis with t-PA encapsulated in NPs shelled with CS or CS-GRGD distinctly differed from those dissolved with t-PA solutions in this in vitro thrombolysis model, These findings may be relevant to posttreatment of patients with conventional PA thrombolysis. |
| Author | Chung, Tze-Wen Chou, Nai-Kuan Wang, Shoei-Shen |
| Author_xml | – sequence: 1 givenname: Shoei-Shen surname: Wang fullname: Wang, Shoei-Shen organization: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China – sequence: 2 givenname: Nai-Kuan surname: Chou fullname: Chou, Nai-Kuan organization: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan, Republic of China – sequence: 3 givenname: Tze-Wen surname: Chung fullname: Chung, Tze-Wen email: twchung@yuntech.edu.tw organization: Department of Chemical Engineering, National Yunlin University of Science and Technology, Dou-Liu, Yunlin, Taiwan, Republic of China |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/19051299$$D View this record in MEDLINE/PubMed |
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| References_xml | – reference: D'souza SE,Ginsberg MH,Plow EF. RGD: A cell adhesion motif. Trends Biol Sci 1991; 16: 246-250. – reference: Chung TW,Lu YF,Wang SS,Lin YS,Chu SH. Growth of human endothelial cells on the photo-chemically grafted Gly-Arg-Gly-Asp (GRGD) chitosans. Biomaterials 2002; 23: 4803-4804. – reference: Ouriel K Thrombolytic therapy acute arterial occlusion. J Am Coll Surg 2002; 194( Suppl 1): 32-39. – reference: Anand S,Kudallur V,Pitma EB,Diamond SL. Mechamisms by which thrombolytic therapy results in nonuniform lysis and residual thrombus after reperfusion. Ann Biomed Eng 1997; 25: 964-974. – reference: Kumar RMNV,Bakowsky U,Lehr CM. Preparation and characterization of cationic PLGA nanoparticles as DNA carriers. Biomaterials 2004; 25: 1771-1777. – reference: Ruoslahti E,Pierschbacher MD. New perspectives in cell adhesion: RGD and integrins. Science 1987; 238: 491-497. – reference: Panyam J,Labhasetwar V. Biodegradable nanoparticles for drug and gene delivery to cells and tissue. Adv Drug Deliv Rev 2003; 55: 329-347. – reference: Heeremans JLM,Prevost R,Bekkers MEA,Los P,Emeis JJ,Kluft C,Crommelin DJ. Thrombolytic treatment with tissue-type plasminogen activators (t-PA) containing liposomes in rabbit: A comparison with free t-PA. Thromb Haemost 1995; 73: 488-494. – reference: Wang SS,Yang MG,Chung TW. Liposomes/chitosan scaffold/human fibrin gel composite system for delivery hydrophilic drugs-release behaviors of Tirofiban in vitro. Drug Deliv 2008; 15: 148-157. – reference: Leach JK,Patterson E,O'Rear EA. Distributed intraclot thrombolysis: Mechanism of accelerated thrombolysis with encapsulated plasminogen activators. J Thromb Haemost 2004; 2: 1548-1555. – reference: Lanza RP,Langer R,Vancanti J, editors. Principles of Tissue Engineering,2nd ed. San Diego, CA: Academic Press; 2000. – reference: Marder V. Thrombolytic therapy. Blood Rev 2001; 15: 143-157. – reference: Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev 2007; 21: 131-142. – reference: Chung TW,Liu DZ,Yang JD,Hsieh JH,Fan XCJ.H Chen JH. Characterizing poly(ϵ-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for Doxorubicin (DOX) delivery: Effects of crosslinked of amine groups. J Nanosci Nanotechnol 2006; 6: 2915-2927. – reference: Yamamoto H,Kuno Y,Sugimoto S,Takeuchi H,Kawashima Y. Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions. J Control Rel 2005; 102: 373-382. – reference: Andersen HR,Nielsen TT,Rasmussen K,Thuesen L,Kelbaek H,Thayssen P,Abildgaard U,Pedersen F,Madsen JK,Grande P,Villadsen AB,Krusell LR,Haghfelt T,Lomholt P,Husted SE,Vigholt E,Kjaergard HK,Mortensen LS,for the DANAMI-2 Investigators. A comparison of coronary angioplasty with fibrinolytic therapy in acute myocardial infarction. N Engl J Med 2003; 349: 733-742. – reference: Xu Y,Du Y. Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles. Int J Pharm 2003; 250: 215-226. – reference: Leach JK,O'Rear EA,Patterson E,Miao Y,Johnson AE. Accelerated thrombolysis in a rabbit model of carotid artery thrombosis with liposome-encapsulated and microencapsulated streptokinase. Thromb Haemost 2003; 90: 64-70. – reference: Wu J-H,Siddiqui K,Diamond SL. Transport phenomena and clot dissolving therapy: An experimental investigation of diffusion-controlled and permeation-enhanced fibrinolysis. Thromb Haemost 1994; 72: 105-112. – reference: Anand S,Wu JH,Diamond SL. Enzyme-mediated proteolysis of fibrous biopolymers: Dissolution front movement in fibrin or collagen under conditions of diffusive or convective transport. Biotech Bioeng 1995; 48: 89-107. – reference: Chung TW,Wang SSTsai WJ. Accelerating thrombolysis with chitosan-coated plasminogen activators encapsulated in poly(lactide-co-glycolide) (PLGA) nanoparticles. 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treatment with tissue‐type plasminogen activators (t‐PA) containing liposomes in rabbit: A comparison with free t‐PA publication-title: Thromb Haemost – volume: 29 start-page: 228 year: 2008 end-page: 237 article-title: Accelerating thrombolysis with chitosan‐coated plasminogen activators encapsulated in poly(lactide‐ ‐glycolide) (PLGA) nanoparticles publication-title: Biomaterials – volume: 48 start-page: 89 year: 1995 end-page: 107 article-title: Enzyme‐mediated proteolysis of fibrous biopolymers: Dissolution front movement in fibrin or collagen under conditions of diffusive or convective transport publication-title: Biotech Bioeng – volume: 23 start-page: 4803 year: 2002 end-page: 4804 article-title: Growth of human endothelial cells on the photo‐chemically grafted Gly‐Arg‐Gly‐Asp (GRGD) chitosans publication-title: Biomaterials – volume: 16 start-page: 246 year: 1991 end-page: 250 article-title: RGD: A cell adhesion motif publication-title: Trends Biol Sci – volume: 21 start-page: 131 year: 2007 end-page: 142 article-title: Thrombin generation and fibrin clot structure publication-title: Blood Rev – year: 2000 – volume: 250 start-page: 215 year: 2003 end-page: 226 article-title: Effect of molecular structure of chitosan on protein delivery properties of chitosan nanoparticles publication-title: Int J Pharm – volume: 102 start-page: 373 year: 2005 end-page: 382 article-title: Surface‐modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions publication-title: J Control Rel – volume: 15 start-page: 148 year: 2008 end-page: 157 article-title: Liposomes/chitosan scaffold/human fibrin gel composite system for delivery hydrophilic drugs‐release behaviors of Tirofiban in vitro publication-title: Drug Deliv – volume: 55 start-page: 329 year: 2003 end-page: 347 article-title: Biodegradable nanoparticles for drug and gene delivery to cells and tissue publication-title: Adv Drug Deliv Rev – volume: 6 start-page: 2915 year: 2006 end-page: 2927 article-title: Characterizing poly(ϵ‐caprolactone)‐ ‐chitooligosaccharide‐ ‐poly(ethylene glycol) (PCP) copolymer micelles for Doxorubicin (DOX) delivery: Effects of crosslinked of amine groups publication-title: J Nanosci Nanotechnol – volume: 72 start-page: 105 year: 1994 end-page: 112 article-title: Transport phenomena and clot dissolving therapy: An experimental investigation of diffusion‐controlled and permeation‐enhanced fibrinolysis publication-title: Thromb Haemost – volume: 2 start-page: 1548 year: 2004 end-page: 1555 article-title: Distributed intraclot thrombolysis: Mechanism of accelerated thrombolysis with encapsulated plasminogen activators publication-title: J Thromb Haemost – volume: 194 start-page: 32 issue: Suppl 1 year: 2002 end-page: 39 article-title: Thrombolytic therapy acute arterial occlusion publication-title: J Am Coll Surg – volume: 25 start-page: 964 year: 1997 end-page: 974 article-title: Mechamisms by which thrombolytic therapy results in nonuniform lysis and residual thrombus after reperfusion publication-title: Ann Biomed Eng – ident: e_1_2_7_17_2 doi: 10.1016/S0142-9612(02)00231-4 – ident: e_1_2_7_9_2 doi: 10.1055/s-0038-1653802 – ident: e_1_2_7_10_2 doi: 10.1055/s-0037-1613600 – ident: e_1_2_7_8_2 doi: 10.1056/NEJMoa025142 – ident: e_1_2_7_11_2 doi: 10.1111/j.1538-7836.2004.00884.x – ident: e_1_2_7_5_2 doi: 10.1016/j.jconrel.2004.10.010 – ident: e_1_2_7_22_2 doi: 10.1016/S1072-7515(01)01053-5 – volume-title: Principles of Tissue Engineering year: 2000 ident: e_1_2_7_14_2 – ident: e_1_2_7_4_2 doi: 10.1016/j.biomaterials.2003.08.069 – ident: e_1_2_7_18_2 doi: 10.1166/jnn.2006.450 – ident: e_1_2_7_2_2 doi: 10.1016/S0169-409X(02)00228-4 – ident: e_1_2_7_13_2 doi: 10.1002/bit.260480203 – ident: e_1_2_7_16_2 doi: 10.1016/0968-0004(91)90096-E – ident: e_1_2_7_20_2 doi: 10.1007/BF02684132 – volume: 72 start-page: 105 year: 1994 ident: e_1_2_7_12_2 article-title: Transport phenomena and clot dissolving therapy: An experimental investigation of diffusion‐controlled and permeation‐enhanced fibrinolysis publication-title: Thromb Haemost doi: 10.1055/s-0038-1648820 – ident: e_1_2_7_6_2 doi: 10.1016/j.biomaterials.2007.09.027 – ident: e_1_2_7_15_2 doi: 10.1126/science.2821619 – ident: e_1_2_7_19_2 doi: 10.1080/10717540801952456 – ident: e_1_2_7_21_2 doi: 10.1016/j.blre.2006.11.001 – ident: e_1_2_7_7_2 doi: 10.1054/blre.2001.0161 – ident: e_1_2_7_3_2 doi: 10.1016/S0378-5173(02)00548-3 |
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| Snippet | Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs)... Accelerated thrombolysis by pressure‐driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs)... Accelerated thrombolysis by pressure-driven permeation has been demonstrated in in vitro and in vivo animal models by using plasminogen activators (PAs)... |
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| SubjectTerms | Animals Biomedical materials Blood Coagulation - drug effects Cattle Chitosan - chemistry Dissolution dissolving patterns of clots Drug Delivery Systems Encapsulation Humans In Vitro Techniques In vitro testing in vitro thrombolysis model Lactic Acid - chemistry Mathematical models Nanoparticles - chemistry Nanotechnology - methods Oligopeptides - chemistry Penetration Permeation permeation through patterns PLGA/CS-GRGD NPs Polyglycolic Acid - chemistry Recombinant Proteins - therapeutic use Spectroscopy, Fourier Transform Infrared Surgical implants Thrombolytic Therapy - methods Tissue Plasminogen Activator - chemistry |
| Title | The t-PA-encapsulated PLGA nanoparticles shelled with CS or CS-GRGD alter both permeation through and dissolving patterns of blood clots compared with t-PA solution: An in vitro thrombolysis study |
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