title: Poly(ethylene glycol)--oligolactates with monodisperse hydrophobic blocks: preparation, characterization, and behavior in water.
abstract: Methoxypoly(ethylene glycol)-b-oligo-L-lactate (mPEG-b-OLA) diblock oligomers with monodisperse OLA blocks were obtained by fractionation of polydisperse block oligomers using preparative HPLC. The fractionated oligomers were composed of an mPEG block with a molecular weight of 350, 550, or 750 and an OLA block with a degree of polymerization of 4, 6, 8, or 10. The diblock oligomers with a low PEG content were fully amorphous, with glass transition temperatures ranging from -60 to -20 degrees C, indicating that the blocks were miscible. Upon heating aqueous dispersions of the block oligomers, cloud points, depending on the PEG/OLA ratio of the block oligomer, were observed at temperatures above 40 degrees C. The monodispersity of the hydrophobic block enabled the amphiphilic molecules to form nanoparticles in water with a hydrodynamic radius of 130-300 nm, at concentrations above the critical aggregation concentration (0.4-1 mg/mL), whereas polydisperse mPEG-b-OLAs gave formation of large aggregates. Static light scattering measurements showed that the nanoparticles have a low density (0.6-25 mg/mL), indicating that the particles are highly hydrated. In agreement herewith, the (1)H NMR spectra of nanoparticles in D2O closely resembled spectra in a good solvent for both blocks (CDCl3). It is therefore suggested that the nanoparticles contain a hydrated core of mPEG-b-OLA block oligomers, stabilized by a thin outer PEG layer. The particles were stable for two weeks, except for the mPEG350 series and mPEG750-b-OLA4, indicating that both the PEG block size and the PEG weight fraction of the oligomers determine their stability. The evident self-emulsifying properties of mPEG-b-oligo-l-lactates with monodisperse hydrophobic blocks as demonstrated in this study, together with their expected biocompatibility and biodegradability, make these systems well suitable for pharmaceutical applications.
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Pharmaceutical Sciences, Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands.
authors.forename: Myrra G
authors.initials: MG
authors.lastname: Carstens
authors.forename: Cornelus F
authors.initials: CF
authors.lastname: van Nostrum
authors.forename: Aissa
authors.initials: A
authors.lastname: Ramzi
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Meeldijk
authors.forename: Ruud
authors.initials: R
authors.lastname: Verrijk
authors.forename: Leo L
authors.initials: LL
authors.lastname: de Leede
authors.forename: Daan J A
authors.initials: DJ
authors.lastname: Crommelin
authors.forename: Wim E
authors.initials: WE
authors.lastname: Hennink