A new biocompatible nanoparticle delivery system for the release of fibrinolytic drugs.
The preparation of novel biocompatible polymeric nanoconstructs suitable to load sensitive bioactive protein agents is reported. Nanoparticles were prepared as based on hybrid polymeric matrices consisting of synthetic bioerodible alternating copolymers of maleic anhydride and n-butylvinylether hemiesterified with 2-methoxyethanol and grafted with poly(ethylene glycol) segments and monoclonal antibody single chain fragment specific for fibrin clot. The prepared nanoparticles were loaded with proteolytic enzymes (trypsin and urokinase), encapsulating up to 2500UI of urokinase/mg of dried nanoparticles. The release of the enzyme from nanoparticles resulted time controlled and it was assessed that in case of administration of urokinase-loaded nanoparticles, the enzyme would preserve its thrombolytic properties more efficiently in respect to free drug administration. Moreover, the nanoparticles showed a good in vitro biocompatibility, suitable for biomedical applications. The stability (shelf life) of the prepared nanostructured dosage forms was evaluated. The drug-loaded nanoparticles resulted stable under stressed conditions (35 degrees C for 13 weeks) in a lyophilized form and preserved their morphological and functional characteristics when stored in suspension for 18 months at 4 degrees C.
Piras
Anna Maria
AM
Laboratory of Bioactive Polymeric Materials for Biomedical and Environmental Applications (BIOlab)-UdR INSTM, Department of Chemistry & Industrial Chemistry, University of Pisa, Via Vecchia Livornese 1291, 56010 S. Piero a Grado, Pisa, Italy.
Chiellini
Federica
F
Fiumi
Chiara
C
Bartoli
Cristina
C
Chiellini
Emo
E
Fiorentino
Bruno
B
Farina
Claudio
C
D016475:3T3 Cells; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics; D001672:Biocompatible Materials; D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D004563:Electrochemistry; D005026:Ethylene Glycols; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007202:Indicators and Reagents; D008299:Maleic Anhydrides; D051379:Mice; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D010316:Particle Size; D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D011208:Powders; D012709:Serum Albumin / Q000737:chemistry; D012995:Solubility; D014357:Trypsin / Q000008:administration & dosage / Q000737:chemistry; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000737:chemistry
D000911:Antibodies, Monoclonal; D001672:Biocompatible Materials; D005026:Ethylene Glycols; D005343:Fibrinolytic Agents; D007140:Immunoglobulin Fab Fragments; D007202:Indicators and Reagents; D008299:Maleic Anhydrides; D014677:Pharmaceutical Vehicles; D011208:Powders; D012709:Serum Albumin; D011092:Polyethylene Glycols; D014357:Trypsin; D014568:Urokinase-Type Plasminogen Activator; C005219:methyl cellosolve