pH-responsive hydrogel cubes for release of doxorubicin in cancer cells

Kozlovskaya, Veronika; Chen, Jun; Tedjo, Chrysanty; Lü, Xing; Campos-Gómez, Javier; Oh, Ji Su; Saeed, Mohammad; Lungu, Claudiu T.; Kharlampieva, Eugenia

doi:10.1039/c4tb00165f

Cited by 64 publications

(89 citation statements)

References 91 publications

(85 reference statements)

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“…The (PMAA CS ) 5 hydrogel particles showed a swelling profile similar to that of our previously demonstrated nondegradable EDA-linked hydrogel particles. 16 However, the overall swelling ratios (the ratio of the particle size at a certain pH to the minimum size of the hydrogel particle at pH = 5) were smaller than those of the EDA-crosslinked cubes or spheres, which underwent a nearly twofold reversible swell/shrink response to pH variations. 16 The lower 1.5−1.2-fold swelling ratios of the (PMAA CS ) 5 biodegradable hydrogels can be explained by a more hydrophobic nature of those structures because of a more hydrophobic CS linker as discussed above for planar PMAA CS hydrogels.…”

Section: Acs Applied Materials and Interfacesmentioning

confidence: 99%

Intracellular Degradable Hydrogel Cubes and Spheres for Anti-Cancer Drug Delivery

Xue¹,

Kozlovskaya²,

Liu³

et al. 2015

ACS Appl. Mater. Interfaces

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Shape and responsiveness of nanoengineered delivery carriers are crucial characteristics for rapid and efficient delivery of therapeutics. We report on a novel type of micrometer-sized hydrogel particles of controlled shape with dual pH- and redox-sensitivity for intracellular delivery of anticancer drugs. The cubical and spherical poly(methacrylic acid) (PMAA) networks with disulfide links are obtained by cross-linking PMAA with cystamine within hydrogen-bonded multilayers of PMAA/poly(vinylpyrrolidone) (PMAA/PVPON) on sacrificial mesoporous templates. The pH-triggered hydrogel swelling/shrinkage not only affords effective doxorubicin entrapment but also efficient endosomal/lysosomal escape, and redox-triggered degradation provides drug release into the cytosolic space. The hydrogels degrade rapidly to low molecular weight chains in the presence of the typical intracellular concentration of glutathione, which should ensure a rapid renal clearance in vivo. Particle shape is found to affect internalization at the initial step of cell-particle interactions. Drug-loaded spherical particles are found to be 12% more cytotoxic than the corresponding cubes within the first 10 h of cell incubation suggesting more rapid internalization of spheres. Both doxorubicin-loaded hydrogel cubes and spheres demonstrate 50% and 90% cytotoxicity when incubated with HeLa cancer cells for 24 and 48 h, respectively. The presented approach integrates the advantages of pH-sensitivity, enzymatic degradation, and shape-regulated internalization for novel types of "intelligent" three-dimensional networks with programmable behavior for use in controlled delivery of therapeutics.

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Section: Acs Applied Materials and Interfacesmentioning

confidence: 99%

Intracellular Degradable Hydrogel Cubes and Spheres for Anti-Cancer Drug Delivery

Xue¹,

Kozlovskaya²,

Liu³

et al. 2015

ACS Appl. Mater. Interfaces

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“…The viability of A549 and HeLa cancer cells was significantly decreased upon interaction with DOX-loaded cubic hydrogels. [11] Anirudhan et al [12] prepared a gelatin-based pH-responsive composite hydrogel by grafting b-cyclodextrin (b-CD) to gelatin (Gel) and crosslinking with oxidized dextran (OX-Dex), and the as-prepared pH-sensitive b-CD-grafted Gel crosslinked with OX-Dex (b-CD-g-Gel/OX-Dex) or composite hydrogel (CHG) was used to investigate the colon delivery of the anticancer drug 5-fluorouracil (5-FLU). They found that the grafting of b-CD enhanced the drug encapsulation capacity and that the drug release profile followed the Higuchi model.…”

Section: Organic-materials-based Ph-responsive Drug-delivery Systemsmentioning

confidence: 97%

“…The DOX-loaded hydrogels could be taken up quickly by human glioma through endocytosis and then bi-odegraded to release the loaded drug, which led to a good antitumor efficacy. [10] Kozlovskaya et al [11] reported on a novel type of hydrogel microparticle that underwent large, rapid, and reversible volume changes in response to the pH value. They prepared cubic hydrogels as interconnected poly(methacrylic acid) network replicas of mesoporous manganese oxide templates by sequential infiltration of poly(methacrylic acid) and poly(N-vinylpyrrolidone), followed by crosslinking of poly(-methacrylic acid) and template dissolution.…”

Section: Organic-materials-based Ph-responsive Drug-delivery Systemsmentioning

confidence: 98%

pH‐Responsive Drug‐Delivery Systems

Zhu

Chen

2014

Chemistry An Asian Journal

168

104

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In many biomedical applications, drugs need to be delivered in response to the pH value in the body. In fact, it is desirable if the drugs can be administered in a controlled manner that precisely matches physiological needs at targeted sites and at predetermined release rates for predefined periods of time. Different organs, tissues, and cellular compartments have different pH values, which makes the pH value a suitable stimulus for controlled drug release. pH-Responsive drug-delivery systems have attracted more and more interest as "smart" drug-delivery systems for overcoming the shortcomings of conventional drug formulations because they are able to deliver drugs in a controlled manner at a specific site and time, which results in high therapeutic efficacy. This focus review is not intended to offer a comprehensive review on the research devoted to pH-responsive drug-delivery systems; instead, it presents some recent progress obtained for pH-responsive drug-delivery systems and future perspectives. There are a large number of publications available on this topic, but only a selection of examples will be discussed.

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“…Among stimulus-sensitive hydrogels, pH-responsible hydrogels, derived from both natural and synthetic polymers, have been investigated intensively [16,17]. This unique class of hydrogels may find significant applications.…”

Section: Introductionmentioning

confidence: 99%

Chiral, pH-sensitive polyacrylamide hydrogels: Preparation and enantio-differentiating release ability

Cheng

Liu

Xie

et al. 2015

Polymer

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pH-responsive hydrogel cubes for release of doxorubicin in cancer cells

Abstract: Doxorubicin (DOX)-loaded poly(methacrylic acid) hydrogel cubes release the drug at pH <5. These hydrogels are developed for shape-directed cellular uptake for drug delivery.

Cited by 64 publications

References 91 publications

Intracellular Degradable Hydrogel Cubes and Spheres for Anti-Cancer Drug Delivery

Intracellular Degradable Hydrogel Cubes and Spheres for Anti-Cancer Drug Delivery

pH‐Responsive Drug‐Delivery Systems

Chiral, pH-sensitive polyacrylamide hydrogels: Preparation and enantio-differentiating release ability

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