title: NMR cryoporometry characterisation studies of the relation between drug release profile and pore structural evolution of polymeric nanoparticles.
abstract: PLGA/PLA polymeric nanoparticles could potentially enhance the effectiveness of convective delivery of drugs, such as carboplatin, to the brain, by enabling a more sustained dosage over a longer time than otherwise possible. However, the link between the controlled release nanoparticle synthesis route, and the subsequent drug release profile obtained, is not well-understood, which hinders design of synthesis routes and availability of suitable nanoparticles. In particular, despite pore structure evolution often forming a key aspect of past theories of the physical mechanism by which a particular drug release profile is obtained, these theories have not been independently tested and validated against pore structural information. Such validation is required for intelligent synthesis design, and NMR cryoporometry can supply the requisite information. Unlike conventional pore characterisation techniques, NMR cryoporometry permits the investigation of porous particles in the wet state. NMR cryoporometry has thus enabled the detailed study of the evolving, nanoscale structure of nanoparticles during drug release, and thus related pore structure to drug release profile in a way not done previously for nanoparticles. Nanoparticles with different types of carboplatin drug release profiles were compared, including burst release, and various forms of delayed release. ESEM and TEM images of these nanoparticles also provided supporting data showing the rapid initial evolution of some nanoparticles. Different stages, within a complex, varying drug release profile, were found to be associated with particular types of changes in the nanostructure which could be distinguished by NMR. For a core-coat nanoparticle formulation, the development of smaller nanopores, following an extended induction period with no structural change, was associated with the onset of substantial drug release. This information could be used to independently validate the rationale for a particular synthesis method. Hence, the specific reasons for the effectiveness of the synthesis route, for obtaining core-coat nanoparticles with delayed release, have been elucidated.
authors.affiliation: Department of Chemical and Environmental Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK.
authors.forename: Navin
authors.initials: N
authors.lastname: Gopinathan
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: John P
authors.initials: JP
authors.lastname: Lowe
authors.affiliation: Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Edler
authors.affiliation: Department of Chemical and Environmental Engineering, University of Nottingham, University Park, Nottingham NG7 2RD, UK. Electronic address: enzspr@exmail.nottingham.ac.uk.
authors.forename: Sean P
authors.initials: SP
authors.lastname: Rigby
mesh_terms: D016190:Carboplatin / Q000737:chemistry*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008956:Models, Chemical; D053758:Nanoparticles; D036103:Nanotechnology; D011091:Polyesters; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D012822:Silicon Dioxide / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods*; D044366:Transition Temperature
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide); D012822:Silicon Dioxide; D016190:Carboplatin
keywords: Controlled release; Cryoporometry; Diffusion; Drug; NMR; PLGA
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