title: Block copolypeptide nanoparticles for the delivery of ocular therapeutics.
abstract: Self-assembling block copolypeptides were prepared by sequential ring-opening polymerization of N-carboxyanhydride (NCA) derivatives of γ-benzyl-L-glutamic acid and ε-carbobenzyloxy-L-lysine, followed by selective deprotection of the benzyl glutamate block. The synthesized polymers had number average molecular weights close to theoretical values, and had low dispersities (ĐM  = 1.15-1.28). Self-assembly of the amphiphilic block copolymers into nanoparticles was achieved using the "solvent-switch" method, whereby the polymer was dissolved in THF and water and the organic solvent removed by rotary evaporation. The type of nanostructures formed varied from spherical micelles to a mixture of spherical and worm-like micelles, depending on copolymer composition. The spherical micelles had an average diameter of 43 nm by dynamic light scattering, while the apparent diameter of the mixed phase system was around 200 nm. Reproducibility of nanoparticle preparation was demonstrated to be excellent; almost identical DLS traces were obtained over three repeats. Following qualitative dye-solubilization experiments, the nanoparticles were loaded with the ocular anti-inflammatory drug dexamethasone. Loading efficiency of the nanoparticles was 90% and the cumulative drug release was 94% over 16 d, with a 20% burst release in the first 24 h.
authors.affiliation: Department of Chemistry, Durham University, South Road, Durham, DH1 3LE, UK.
authors.forename: Timo
authors.initials: T
authors.lastname: Stukenkemper
authors.forename: Anica
authors.initials: A
authors.lastname: Dose
authors.forename: Maria
authors.initials: M
authors.lastname: Caballo Gonzalez
authors.forename: Alexander J J
authors.initials: AJ
authors.lastname: Groenen
authors.forename: Sarah
authors.initials: S
authors.lastname: Hehir
authors.forename: Vanessa
authors.initials: V
authors.lastname: Andrés-Guerrero
authors.forename: Rocio
authors.initials: R
authors.lastname: Herrero Vanrell
authors.forename: Neil R
authors.initials: NR
authors.lastname: Cameron
mesh_terms: D000812:Anhydrides / Q000138:chemical synthesis / Q000737:chemistry*; D003907:Dexamethasone; D004337:Drug Carriers / Q000138:chemical synthesis*; D015195:Drug Design; D005128:Eye Diseases / Q000188:drug therapy*; D005971:Glutamates / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D008823:Micelles; D015394:Molecular Structure; D050997:Nanomedicine / Q000379:methods* / Q000639:trends; D053758:Nanoparticles / Q000737:chemistry* / Q000627:therapeutic use; D010078:Oxazines; D010455:Peptides / Q000737:chemistry*; D011099:Polyglutamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D000812:Anhydrides; D004337:Drug Carriers; D005971:Glutamates; D008823:Micelles; D010078:Oxazines; D010455:Peptides; C568827:gamma-benzylglutamyl-N-carboxy anhydride; C003172:poly-gamma-benzyl-L-glutamate; D011099:Polyglutamic Acid; D003907:Dexamethasone; C044808:nile red
keywords: block copolymers; drug delivery systems; nanoparticles; polypeptides; ring-opening polymerization