Elaboration of densely functionalized polylactide nanoparticles from N -acryloxysuccinimide-based block copolymers (original) (raw)
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Reactive and Functional Polymers, 2012
Novel functionalized nanoporous polymeric materials could be derived from poly(D,L-lactide)-blockpolystyrene (PLA-b-PS) diblock copolymers with a sulfonyl group at the junction between both blocks were synthesized by a combination of ring-opening polymerization (ROP) and atom transfer radical polymerization (ATRP) using a synthetic difunctional initiator through a three-step sequential methodology. Different x-bromo PLA polymers with various molar masses ranging from 3640 to 11,440 g mol À1 were first produced by coupling x-hydroxy PLA precursors to a chlorosulfonyl-functionalized ATRP initiator previously prepared, thus leading to the formation of suitable macroinitiators for the subsequent ATRP polymerization of styrene. Consequently, PLA-b-PS diblock copolymers were obtained with a finely tuned PLA volume fraction (f PLA) in order to develop a microphased-separation morphology. The resulting copolymers as well as the intermediate compounds were carefully analyzed by size exclusion chromatography and 1 H NMR. Upon shear flow induced by a channel die processing, oriented copolymers were generally afforded as characterized by small-angle-X-ray scattering (SAXS). Such copolymers were finally submitted to mild alkaline conditions so as to hydrolyze the sacrificial PLA block, and the presence of the sulfonic acid functionality on the pore walls of the resulting nanoporous materials was evidenced by means of a post-modification reaction consisting in the corresponding sulfonamide formation.
Journal of Biomaterials Science, Polymer Edition, 2003
Fully biodegradable and surface-functionalized poly(D,L-lactide) (PLA) nanoparticles have been prepared by a co-precipitation technique. Novel amphiphilic random copolyesters P(CL-co-γXCL) were synthesized by controlled copolymerization of ε-caprolactone and ε-caprolactone substituted in the γ-position by a hydrophilic X group, where X is either a cationic pyridinium (γPyCL) or a non-ionic hydroxyl (γOHCL). Nanoparticles were prepared by co-precipitation of PLA with the P(CL-co-γXCL) copolyester from a DMSO solution. Small amounts of cationic P(CL-co-γPyCL) copolymers are needed to quantitatively form stable nanoparticles (ca. 10 mg/100 mg PLA), although larger amounts of non-ionic P(CL-co-γOHCL) copolymers are needed (≥12.5 mg/100 mg PLA). Copolymers with a low degree of polymerization (ca. 40) are more efficient stabilizers, probably because of faster migration towards the nanoparticle-water interface. The nanoparticle diameter decreases with the polymer concentration in DMSO, e.g. from ca. 160 nm (16 mg/ml) to ca. 100 nm (2 mg/ml) for PLA/P(CL-co-γPyCL) nanoparticles. Migration of the P(CL-co-γXCL) copolyesters to the nanoparticle surface was confirmed by measurement of the zeta potential, i.e. ca. +65 mV for P(CL-co-γPyCL) and-7 mV for P(CL-co-γOHCL). The polyamphiphilic copolyesters stabilize PLA nanoparticles by electrostatic or steric repulsions, depending on whether they are charged or not. They also impart functionality and reactivity to the surface, which opens up new opportunities for labelling and targeting purposes.
International Journal of Pharmaceutics, 2010
In order to evaluate the solubility effect of grafted moiety on the physicochemical properties of poly(d,llactide) (PLA) based nanoparticles (NPs), two materials of completely different aqueous solubility, polyethylene glycol (PEG) and palmitic acid were grafted on PLA backbone at nearly the same grafting density, 2.5% (mol of grafted moiety/mol of lactic acid monomer). Blank and ibuprofen-loaded NPs were fabricated from both polymers and their properties were compared to PLA homopolymer NPs as a control. NPs were analyzed for major physicochemical parameters such as encapsulation efficiency, size and size distribution, surface charge, thermal properties, surface chemistry, % poly(vinyl alcohol) (PVA) adsorbed at the surface of NPs, and drug release pattern. Encapsulation efficiency of ibuprofen was found to be nearly the same for both polymers ∼36% and 39% for PEG2.5%-g-PLA and palmitic acid2.5%-g-PLA NPs, respectively. Lyophilized NPs of palmitic acid2.5%-g-PLA either blank or loaded showed larger hydrodynamic diameter (∼180 nm) than PEG2.5%-g-PLA NPs (∼135 nm). PEG2.5%-g-PLA NPs showed lower % of PVA adsorbed at their surface (∼5%, w/w) than palmitic acid2.5%-g-PLA NPs (∼10%, w/w). Surface charge of palmitic acid2.5%-g-PLA NPs seems to be influenced by the large amount of PVA remains associated within their matrix. Thermal analysis using DSC revealed possible drug crystallization inside NPs. Both AFM phase imaging and XPS studies revealed the tendency of PEG chains to migrate towards the surface of PEG2.5%-g-PLA NPs. While, XPS analysis of palmitic acid2.5%-g-PLA NPs showed the tendency of palmitate chains to position themselves into the inner core of the forming particle avoiding facing the aqueous phase during NPs preparation using O/W emulsion method. The in vitro release pattern showed that PEG2.5%-g-PLA NPs exhibited faster release rates than palmitic acid2.5%-g-PLA NPs. PEG and palmitate chains when grafted onto PLA backbone, different modes of chain organization during NPs formation were obtained, affecting the physicochemical properties of the obtained NPs. The obtained results suggest that the properties of PLA-based NPs can be tuned by judicious selection of both chemistry and solubility profile of grafted material over PLA backbone.
Polymer Chemistry, 2021
Polymerization-induced self-assembly (PISA) is widely recognized to be a powerful technique for the preparation of diblock copolymer nano-objects in various solvents. Herein a highly unusual non-aqueous emulsion polymerization formulation is reported. More specifically, the reversible addition-fragmentation chain transfer (RAFT) polymerization of N-(2-acryloyloxy)ethyl pyrrolidone (NAEP) is conducted in n-dodecane using a poly(stearyl methacrylate) (PSMA) precursor to produce sterically-stabilized spherical nanoparticles at 90°C. This relatively high polymerization temperature was required to ensure sufficient background solubility for the highly polar NAEP monomer, which is immiscible with the non-polar continuous phase. A relatively long PSMA precursor (mean degree of polymerization, DP = 36) was required to ensure colloidal stability, which meant that only kinetically-trapped spheres could be obtained. Dynamic light scattering (DLS) studies indicated that the resulting PSMA 36-PNAEP x (x = 60 to 500) spheres were relatively well-defined (DLS polydispersity <0.10) and the z-average diameter increased linearly with PNAEP DP up to 261 nm. Differential scanning calorimetry studies confirmed a relatively low glass transition temperature (T g) for the core-forming PNAEP block, which hindered accurate sizing of the nanoparticles by TEM. However, introducing ethylene glycol diacrylate (EGDA) as a third block to covalently crosslink the nanoparticle cores enabled a spherical morphology to be identified by transmission electron microscopy studies. This assignment was confirmed by small angle X-ray scattering studies of the linear diblock copolymer nanoparticles. Finally, hydrophobic linear PSMA 36-PNAEP 70 spheres were evaluated as a putative Pickering emulsifier for n-dodecane-water mixtures. Unexpectedly, addition of an equal volume of water followed by high-shear homogenization always produced oil-in-water (o/w) emulsions, rather than water-in-oil (w/o) emulsions. Moreover, core-crosslinked PSMA 36-PNAEP 60-PEGDA 10 spheres also produced o/w Pickering emulsions, suggesting that such Pickering emulsions must be formed by nanoparticle adsorption at the inner surface of the oil droplets. DLS studies of the continuous phase obtained after either creaming (o/w emulsion) or sedimentation (w/o emulsion) of the droplet phase were consistent with this interpretation. Furthermore, certain experimental conditions (e.g. ≥0.5% w/w copolymer concentration for linear PSMA 36-PNAEP x nanoparticles, ≥0.1% w/w for core-crosslinked nanoparticles, or n-dodecane volume fractions ≤0.60) produced w/o/w double emulsions in a single step, as confirmed by fluorescence microscopy studies. † Electronic supplementary information (ESI) available. See
Journal of Applied Polymer Science, 2008
The effects of the monomer ratio, surfactant, and crosslinker contents on the particle size and phase-transition behavior of the copolymer poly(N-isopropylacrylamide-co-methacrylic acid) (PNIPAAm-MAA) were investigated with Fourier transform infrared, differential scanning calorimetry, and dynamic laser scattering techniques. In addition to the thermoresponsive property of poly(N-isopropylacrylamide), ionized methacrylic acid groups brought pH sensitivity to the PNIPAAm-MAA copolymer particles. The polymer particle size varied with the amounts of the monomer ratio, surfactant, and crosslinker. As the monomer ratio and crosslinker content increased and the amount of the surfactants decreased, the particle size increased. The influence of the crosslinker content on the particle size was less significant than the effect of the monomer ratio and surfactants. When the temperature increased, the particles tended to shrink and decreased in size to near or below 100 nm. Particle sizes at 208C decreased to less than 100 nm with increased surfactant content. The control of the particle size within the 100-nm range makes PNIPAAm-MAA copolymer particles useful for biomedical and heavy-metal-ion adsorption applications.
European Polymer Journal, 2010
A new kind of thermo-responsive particles were prepared by the self-assembly technique, comprising poly(hydroxyvalerate-co-hydroxybutirate)-b-poly(N-isopropylacrylamide)/ (PHBHV-b-PNIPAAm) block copolymers. The hydrophilic part PNIPAAm was synthesized by Reversible Addition-Fragmentation chain Transfer (RAFT) polymerization. Particles with core-shell morphology were obtained with hydrophilic outer shells and hydrophobic inner cores. Dexametasone acetate (DexAc) was used as a model drug with an encapsulation efficiency of 77%. The release of DexAc in aqueous solution was strongly dependent on temperature, suggesting that PHBHV-b-PNIPAAm particles can be used as a thermo-responsive carrier material with external control in a drug release system.
Colloids and Surfaces A-physicochemical and Engineering Aspects, 2007
Amphiphilic triblock copolymer, poly(p-dioxanone-co-caprolactone)-block-poly(ethylene oxide)-block-poly(p-dioxanone-co-caprolactone) (PPDO-co-PCL-b-PEO-b-PPDO-co-PCL) was synthesized by ring opening polymerization (ROP) of p-dioxanone and -caprolactone initiated through the hydroxyl end of poly(ethylene glycol) (PEG) in the presence of stannous 2-ethyl hexanoate [Sn(oct) 2 ] as a catalyst. Polymerization and structural features of the polymers were analyzed by different physicochemical techniques (GPC, 1 H NMR, 13 C NMR, FT-IR, DSC and TGA). The splitting of 1 H NMR resonance at δ 2.3 and δ 4.1 ppm reveals the random copolymerization. Polymeric nanoparticles were prepared in phosphate buffer (pH 7.4) by co-solvent evaporation technique at room temperature (25 • C). Existence of hydrophobic domains as cores of the micelles were characterized by 1 H NMR spectroscopy and further confirmed with fluorescence technique using pyrene as a probe. Critical micelle concentration (CMC) of the polymer in phosphate buffer (pH. 7.4) was decreased from 2.3 × 10 −3 to 7.6 × 10 −4 g/L with the fraction of PCL. Polymeric nanoparticles observed by atomic force microscopy (AFM) were uniform and spherical, with smooth textured of around 50-30 nm diameter. Dynamic light scattering (DLS) and electrophoretic light scattering (ELS) measurements showed a monodisperse size distribution of around 113-90 nm hydrodynamic diameters and negative zeta (ζ) potential (−4 to −14 mV), respectively. The investigations for the polymeric nanoparticles in aqueous medium showed that the composition of the hydrophobic segment of amphiphilic block copolymer makes a significant influence on its physicochemical characteristics.