A multifunctional biodegradable brush polymer-drug conjugate for paclitaxel/gemcitabine co-delivery and tumor imaging

Abstract

A unique nanosystem enabling paclitaxel/gemcitabine co-delivery and tumor imaging is reported.

Allyl group-containing polyvinylphosphonates as a flexible platform for the selective introduction of functional groups via polymer-analogous transformations

“…As shown in the literature allyl moieties represent flexible anchors to selectively incorporate biological moieties. 42 In addition, DAlVP-containing polymers are advantageous as two ester per monomer unit can double the loading capacity compared to other copolymer systems (polyethers 28,43 or polylactides 44 ). Additionally, the water-solubility can be easily tuned by the DEVP amount.…”

“…Therefore, no solubilizing motifs such as PEG or zwitterions are required. 44–46 In combination with their intrinsic biocompatibility and a polymerization technique, which enables predictable and reproducible polymerization results, these copolymer types emerge as model candidates for biomedical applications. In this study, we took advantage of the allylic groups introduced through DAlVP and explored a variety of organic transformations of unsaturated carbon–carbon bonds in form of polymer-analogous reactions with statistical P(DEVP- co -DAlVP).…”

A Tale of Drug-Carrier Optimization: Controlling Stimuli Sensitivity via Nanoparticle Hydrophobicity through Drug Loading

“…Over the past two decades of development of the field of nanomedicine, large bodies of work have sought to improve the performance of therapeutic agents by using nanoparticle carriers. − In general, emphasis has been on maximizing the drug payload to achieve transport and accumulation in a targeted tissue; − however, effects of the properties and extent of drug loading are often neglected. Drug loading may alter a nanocarrier’s physiochemical properties in a loading-dependent manner, thereby influencing efficacy.…”

“…Drug loading may alter a nanocarrier’s physiochemical properties in a loading-dependent manner, thereby influencing efficacy. For instance, loading of hydrophobic drug molecules within an amphiphilic nanoparticle framework may affect colloidal stability, size, shape, flexibility, internal accessibility, and other parameters, − each of which are important attributes affecting circulation time, clearance, biodistribution, and drug release. − Covalent drug conjugates enable sustained delivery without burst release during circulation, displaying minimized systemic toxicity and increased accumulations in targeted tissue. ,, Furthermore, stimuli-responsive properties provide a preferable spatiotemporal control over payload release, thereby improving therapeutic efficacy while reducing systemic toxicity. ,,,,, Therefore, a thorough knowledge of the role that therapeutics play on the properties of nanomedicines as a function of payload level is of great importance, and control over drug-carrier-media interactions may provide an additional opportunity to tune physicochemical characteristics and biological performance of nanoformulations. As a proof of concept in this study, hydrophobic drugs were conjugated via stimulus-sensitive linkers along the hydrophobic backbone of amphiphilic block copolymers and assembled into nanoscopic micelles to investigate the importance of payload level on stimulus accessibility, drug release, and therapeutic efficacy and selectivity in vitro .…”

“…17−21 Covalent drug conjugates enable sustained delivery without burst release during circulation, displaying minimized systemic toxicity and increased accumulations in targeted tissue. 3,9,16 Furthermore, stimuli-responsive properties provide a preferable spatiotemporal control over payload release, thereby improving therapeutic efficacy while reducing systemic toxicity. 2,5,7,8,22,23 Therefore, a thorough knowledge of the role that therapeutics play on the properties of nanomedicines as a function of payload level is of great importance, and control over drug-carrier-media interactions may provide an additional opportunity to tune physicochemical characteristics and bio-logical performance of nanoformulations.…”