3 research outputs found

    Controlled Delivery of Functionalized Gold Nanoparticles by pH-Sensitive Polymersomes

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    The present study reports on the development of composite gold nanoparticles (AuNPs)/polymersome formulations, based on pH-responsive biocompatible polymer vesicles integrating prefunctionalized AuNPs, doped with a hydrophobic model probe for improved multimodal drug delivery. The polymer vesicles were prepared from an amphiphilic pentablock terpolymer poly­(ε-caprolactone)-<i>b</i>-poly­(ethylene oxide)-<i>b</i>-poly­(2-vinylpyridine)-<i>b</i>-poly­(ethylene oxide)-<i>b</i>-poly­(ε-caprolactone) (PCL-PEO-P2VP-PEO-PCL), consisting of a pH-sensitive and biodegradable P2VP/PCL membrane, surrounded by neutral hydrophilic PEO looping chains. Additionally, partial quaternization of the P2VP block has been performed to introduce cationic moieties. Water-dispersible AuNPs carrying a hydrophobic molecule were encapsulated in the hydrophilic aqueous lumen of the vesicles, and the release was monitored at pH conditions simulating physiological and tumor environments. The complex delivery of the cargos from these vesicles showed improved and controlled kinetics relative to the individual nanocarriers, which could be further tuned by pH and chemical modification of the membrane forming block

    Injectable Hydrogel: Amplifying the pH Sensitivity of a Triblock Copolypeptide by Conjugating the N‑Termini via Dynamic Covalent Bonding

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    We explore the self-assembly behavior of aqueous solutions of an amphiphilic, pH-sensitive poly­(l-alanine)-<i>b</i>-poly­(l-glutamic acid)-<i>b</i>-poly­(l-alanine), (A<sub>5</sub>E<sub>11</sub>A<sub>5</sub>) triblock copolypeptide, end-capped by benzaldehyde through Schiff base reaction. At elevated concentrations and under physiological pH (7.4) and ionic strength (0.15M), the bare copolypeptide aqueous solutions underwent a sol–gel transition after heating and slow cooling thermal treatment, forming opaque stiff gels due to a hierarchical self-assembly that led to the formation of β-sheet-based twisted super fibers (Popescu et al. <i>Soft Matter</i> <b>2015</b>, <i>11</i>, 331–342). The conjugation of the N-termini with benzaldehyde (Bz) through a Schiff base reaction amplifies the copolypeptide pH-sensitivity within a narrow pH window relevant for in vivo applications. Specifically, the dynamic character of the imine bond allowed coupling/decoupling of the Bz upon switching pH. The presence of Bz conjugates to the N-termini of the copolypeptide resulted in enhanced packing of the elementary superfibers into thick and short piles, which inhibited the ability of the system for gelation. However, partial cleavage of Bz upon lowering pH to 6.5 prompted recovery of the hydrogel. The sol–gel transition triggered by pH was reversible, due to the coupling/decoupling of the benzoic–imine dynamic covalent bonding, endowing thus the gelling system with injectability. Undesirably, the gelation temperature window was significantly reduced, which however can be regulated at physiological temperatures by using a suitable mixture of the bare and the Bz-conjugated coplypeptide. This triblock copolypeptide gelator was investigated as a scaffold for the encapsulation of polymersome nanocarriers, loaded with a hydrophilic model drug, calcein. The polymersome/polypeptide complex system showed prolonged probe release in pH 6.5, which is relevant to extracellular tumor environment, rendering the system potentially useful for sustained delivery of anticancer drugs locally in the tumor

    Stimuli-Responsive Amphiphilic Polyelectrolyte Heptablock Copolymer Physical Hydrogels: An Unusual pH-Response

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    An amphiphilic cationic polyelectrolyte based on poly­[2-(dimethylamino)­ethyl methacrylate] (polyDMA) and poly­(<i>n</i>-butyl methacrylate) (polyBuMA) with a BuMA–DMA–BuMA–DMA–BuMA–DMA–BuMA heptablock copolymer architecture was studied in aqueous media. This copolymer was found to form a physical hydrogel via the intermolecular hydrophobic association (physical cross-linking) of the BuMA blocks. The rheological properties of the heptablock hydrogels were investigated as a function of copolymer concentration, and pH. The results showed a peculiar pH-dependence of the rheological properties, remarkably different from those observed with associative telechelic polyelectrolytes. Aqueous solutions of this copolymer were free-flowing sols at low pH (below 2) and high pH (above 8), whereas they turned into gels at intermediate pH values. The rheological properties studied as a function of pH showed two additional stiff–soft–stiff gel transitions at pH 4.5 and 6.5. Small-angle neutron scattering revealed the formation of a 3D transient network of bridged flower-like micelles whose structural characteristics, i.e., micellar radius, hard-sphere radius and hard-sphere volume fraction, were smoothly evolving with the pD