Conventional treatment approaches fail to provide durable control over aggressive malignancies due to intrinsic or acquired drug resistance characteristic of high-risk disease. SN-38, a potent camptothecin analog specifically targeting DNA topoisomerase I cleavage complexes, has shown promise in preclinical studies against aggressive solid tumors. However, its clinical utility is limited by inadequate solubility in pharmaceutically acceptable vehicles and by poor chemical and metabolic stability. Micelles formulated from amphiphilic invertible polymers (AIPs) can address these issues by concomitantly enabling solubilization of waterinsoluble molecular cargoes and by protecting chemically labile agents from inactivation. Furthermore, the inversion of the AIP and disruption of the carrier−drug complexes triggered by contact with cell membranes makes it possible to deliver the therapeutic payload into the cell interior without compromising its biological activity. In the present study, we characterized a novel AIP-based micellar formulation of SN-38 and evaluated its growth inhibitory effect on neuroblastoma (NB) cells derived either at diagnosis or at relapse after intensive chemoradiotherapy. Colloidally stable, drug-loaded micellar assemblies with a uniform <100 nm size were prepared using an AIP consisting of alternating blocks of poly(ethylene glycol) and polytetrahydrofuran (PEG 600 -PTHF 650 ). The micellar drug applied in a low nanomolar range (10−50 nM) completely suppressed the growth of chemo-nai ̈ve NB cells even after a brief (10 min) exposure. Furthermore, extending the exposure to 24 h resulted in a profound and lasting inhibitory effect of the micellar formulation on the growth of NB cells exhibiting an acquired loss of p53 function. These results suggest that micelle-mediated delivery of SN-38 can potentially offer a new and effective strategy for treating different phases of high-risk disease, including those showing poor response to conventional therapies.
Renewable 3-allyl-5-vinylveratrole (AVV) has been evaluated and classified as a biobased cross-linkable vinyl monomer in free-radical chain polymerization. AVV can be readily synthesized in four steps from vanillin, a compound available from lignin. Retained during macromolecular backbone formation, allylic unsaturation can be utilized in post-polymerization crosslinking and contribute to polymer network formation. The glasstransition temperature of the homopolymer from AVV (T g = 77 °C) indicates that incorporating its fragments into copolymers might considerably change the intermolecular interactions and physicochemical properties of the resulting materials. Reactivity ratios (r 1 , r 2 ) obtained in AVV copolymerization with styrene and calculated Q − e parameters of AVV confirm that this monomer copolymerization is described with the classical Mayo−Lewis equation. In this work, latexes from AVV and a renewable acrylic monomer from high oleic soybean oil were synthesized using the miniemulsion process. When the resulting biobased latex films are oxidatively cured, thermomechanical properties of the latex network are determined by the cross-link density, controlled by the ratio of "rigid" and "soft" fragments of AVV and the high oleic soybean oil-based monomer, respectively. Depending on the monomer ratio in the feed, polymeric materials with essentially different viscoelastic behaviors were obtained. Being a structural analogue to styrene, 3-allyl-5-vinylveratrole may function as its renewable replacement in free-radical polymerization, particularly in sustainable latexes. Assuming a variety of plant/vegetable oil-based acrylic monomers available, combining such monomers with AVV can become a promising platform for controlling properties of biobased latex polymer networks and their performance.
We describe here the fabrication, characterization, and properties of tough bioplastics made of a babassu oil-based acrylic polymer (PBBM), hemicellulose xylan grafted with PBBM chains, and carnauba wax (CW). The plastic was primarily designed to obtain bioderived materials that can replace low-density polyethylene (LDPE) in certain food packaging applications. To obtain plastic, the radical polymerization of an original babassu oil-based acrylic monomer (BBM) in the presence of xylan macromolecules modified with maleic anhydride (X-MA) was conducted. The polymerization resulted in a material (PBBM-X) mostly consisting of highly branched PBBM/X-MA macromolecules. PBBM-X has a glass transition of 42 °C, a storage modulus of 130 MPa (at 25 °C, RT), and a Young’s modulus of 30 MPa at RT. To increase the moduli, we blended PBBM-X with carnauba wax, a natural material with a high modulus and a melting temperature of ~80 °C. It was found that PBBM-X is compatible with the wax, as evidenced by the alternation of the material’s thermal transitions and the co-crystallization of BBM side alkyl fragments with CW. As a result, the PBBM-X/CW blend containing 40% of the wax had a storage modulus of 475 MPa (RT) and a Young’s modulus of 248 MPa (RT), which is close to that of LDPE. As polyethylene, the PBBM-X and PBBM-X/CW bioplastics have the typical stress-strain behavior demonstrated by ductile (tough) plastics. However, the bioplastic’s yield strength and elongation-at-yield are considerably lower than those of LDPE. We evaluated the moisture barrier properties of the PBBM-X/(40%)CW material and found that the bioplastic’s water vapor permeability (WVP) is quite close to that of LDPE. Our bioderived material demonstrates a WVP that is comparable to polyethylene terephthalate and lower than the WVP of nylon and polystyrene. Taking into account the obtained results, the fabricated materials can be considered as polyethylene alternatives to provide sustainability in plastics production in the packaging areas where LDPE currently dominates.
This study demonstrated that polymerization behavior of plant oil-based acrylic monomers (POBMs) synthesized in one-step transesterification reaction from naturally rich in oleic acid olive, canola, and high-oleic soybean oils is associated with a varying mass fraction of polyunsaturated fatty acid fragments (linoleic (C18:2) and linolenic (C18:3) acid esters) in plant oil. Using miniemulsion polymerization, a range of stable copolymer latexes was synthesized from 60 wt.% of each POBM and styrene to determine the impact of POBM chemical composition (polyunsaturation) on thermal and mechanical properties of the resulted polymeric materials. The unique composition of each plant oil serves as an experimental tool to determine the effect of polyunsaturated fatty acid fragments on POBM polymerization behavior and thermomechanical properties of crosslinked films made from POBM-based latexes. The obtained results show that increasing polyunsaturation in the copolymers results in an enhanced crosslink density of the latex polymer network which essentially impacts the mechanical properties of the films (both Young’s modulus and toughness). Maximum toughness was observed for crosslinked latex films made from 50 wt.% of each POBM in the monomer feed.
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