Smart branched polymer drug conjugates as nano-sized drug delivery systems

Duro‐Castaño, Aroa; Movellan, Julie; Vicent, Marı́a J.

doi:10.1039/c5bm00166h

Cited by 90 publications

(72 citation statements)

References 145 publications

(173 reference statements)

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“…In addition, the microstructure of the side chains can be controlled to yield core–shell structures with compartments of different polarity. This precise control over size and internal structure may provide solutions to tackle some of the limitations of other drug delivery systems, for example in cancer therapy, where intratumoral pressure substantially limits their penetration . In general, a nanodrug delivery system (NanoDDS) for chemotherapeutics designed with regard to cancer therapy needs to deliver its cargo to the tumor cells.…”

Section: Introductionmentioning

confidence: 99%

“…systems, for example in cancer therapy, where intratumoral pressure substantially limits their penetration. [1][2][3] In general, a nanodrug delivery system (NanoDDS) for chemotherapeutics designed with regard to cancer therapy needs to deliver its cargo to the tumor cells. While for many solid tumors extravasation into intestinal space takes place for nanoparticles and retention is ensured by poor lymphatic drainage, [4,5] deep penetration into the tumor is hardly realized.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis and Characterization of Stimuli‐Responsive Star‐Like Polypept(o)ides: Introducing Biodegradable PeptoStars

Holm

Weber

Heller

et al. 2017

Macromolecular Bioscience

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Star-like polymers are one of the smallest systems in the class of core crosslinked polymeric nanoparticles. This article reports on a versatile, straightforward synthesis of three-arm star-like polypept(o)ide (polysarcosine-block-polylysine) polymers, which are designed to be either stable or degradable at elevated levels of glutathione. Polypept(o)ides are a recently introduced class of polymers combining the stealth-like properties of the polypeptoid polysarcosine with the functionality of polypeptides, thus enabling the synthesis of materials completely based on endogenous amino acids. The star-like homo and block copolymers are synthesized by living nucleophilic ring opening polymerization of the corresponding N-carboxyanhydrides (NCAs) yielding polymeric stars with precise control over the degree of polymerization (X = 25, 50, 100), Poisson-like molecular weight distributions, and low dispersities (Đ = 1.06-1.15). Star-like polypept(o)ides display a hydrodynamic radius of 5 nm (μ < 0.05) as determined by dynamic light scattering (DLS). While star-like polysarcosines and polypept(o)ides based on disulfide containing initiators are stable in solution, degradation occurs at 100 × 10 m glutathione concentration. The disulfide cleavage yields the respective polymeric arms, which possess Poisson-like molecular weight distributions and low dispersities (Đ = 1.05-1.12). Initial cellular uptake and toxicity studies reveal that PeptoStars are well tolerated by HeLa, HEK 293, and DC 2.4 cells.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synthesis and Characterization of Stimuli‐Responsive Star‐Like Polypept(o)ides: Introducing Biodegradable PeptoStars

Holm

Weber

Heller

et al. 2017

Macromolecular Bioscience

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show abstract

“…Polymeric conjugates have received considerable attention in polymer therapeutics wherein the therapeutic molecule is not encapsulated but covalently linked to a polymeric macromolecular backbone via a biodegradable spacer . The conjugation of therapeutic molecules onto polymeric carriers has several advantages, such as enhancement of aqueous solubility, enhanced blood circulation time, protection against proteolytic enzymes, and reduction in renal clearance . Moreover, the biodegradable linkages used to connect these therapeutic molecules to polymers (e.g., amide, ester, hydrazone, and keto) are designed to release the molecules under specific cleavage conditions.…”

Section: Nanoformulations For Betulinic Acid Deliverymentioning

confidence: 99%

Therapeutic applications of betulinic acid nanoformulations

Saneja

Arora

Kumar

et al. 2018

Annals of the New York Academy of Sciences

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Betulinic acid (BA), a naturally occurring plant-derived pentacyclic triterpenoid, has gained attention in recent years owing to its broad-spectrum biological and medicinal properties. Despite the pharmacological activity of BA, it has been associated with some drawbacks, such as poor aqueous solubility and short half-life in vivo, which limit therapeutic application. To solve these problems, much work in recent years has focused on enhancing BA's aqueous solubility, half-life, and efficacy by using nanoscale drug delivery systems. Several different kinds of nanoscale delivery systems-including polymeric nanoparticles, magnetic nanoparticles, liposomes, polymeric conjugates, nanoemulsions, cyclodextrin complexes, and carbon nanotubes-have been developed for the delivery of BA. Here, we focus on the recent developments of novel nanoformulations used to deliver BA in order to improve its efficacy.

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“…Among various parenteral drug delivery systems, dendrimers are attractive materials used in antithrombotic agent delivery. Dendrimers possess a precise control on molecule size, shape, dimension, polarity, flexibility, and solubility by choosing different branching units and surface functional groups, which make them promising new scaffolds for drug delivery system . In particular, peptide dendrimer is a sort of dendritic polymer, which contains peptide bonds in the structure .…”

Section: Introductionmentioning

confidence: 99%

Multiarm‐polyethylene glycol‐polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus

Zhang

Lü

Gao

et al. 2018

J Biomedical Materials Res

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Thrombotic events affect many individuals in a number of ways, all of which can cause significant morbidity and mortality. Nattokinase (NK), as a novel thrombolytic drug, has been used for thrombolytic therapy. It not only possesses plasminogen activator activity, but also directly digests fibrin through limited proteolysis. However, it may undergo inactivation and denaturation in the harsh external environment. In this study, a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer was fabricated and used as a carrier for NK protection and delivery. Different arm numbers of polyethylene glycol-polyglutamic acid peptide dendrimers (x-PEG(G ) , x = 2, 4, 6, 8) were designed, prepared, and characterized by H NMR and FTIR. Then, x-PEG(G ) were loaded with NK to form nanocomposites. Their size and morphology were determined by dynamic light scattering and transmission electron microscopy. Enzyme activity was evaluated via UV-Vis absorbance spectra, fluorescence spectra, circular dichroism spectra, and zeta potential measurements. The study reveals that the obtained x-PEG(G ) /NK nanocomposites possess high enzyme activity. In addition, the nanocomposites show increased viability of rat macrophage cells, and excellent thrombolysis ability in vitro and in vivo. This work establishes a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer with potential application in NK carrier and thrombolytic therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1687-1696, 2018.

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Smart branched polymer drug conjugates as nano-sized drug delivery systems

Abstract: Branched polymers own special properties derived from their intrinsic characteristics. These properties make them ideal candidates to be used as carriers for an improved generation of polymer-drug conjugates.

Cited by 90 publications

References 145 publications

Synthesis and Characterization of Stimuli‐Responsive Star‐Like Polypept(o)ides: Introducing Biodegradable PeptoStars

Synthesis and Characterization of Stimuli‐Responsive Star‐Like Polypept(o)ides: Introducing Biodegradable PeptoStars

Therapeutic applications of betulinic acid nanoformulations

Multiarm‐polyethylene glycol‐polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus

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