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WIREs Nanomed Nanobiotechnol
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Cyclodextrin‐based nanosponges: a versatile platform for cancer nanotherapeutics development

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Nanosponges (NSs) are a new age branched cyclodextrin (CD) polymeric systems exhibiting tremendous potential in pharmaceutical, agro science, and biomedical applications. Over the past decade, different varieties of NS based on the type of CD and the crosslinker have been developed tailored for specific applications. NS technology has been instrumental in achieving solubilization, stabilization, sustained release, enhancement of activity, permeability enhancement, protein delivery, ocular delivery, stimuli sensitive drug release, enhancement of bioavailability, etc. There is a major explosion of research in the area of NS‐aided cancer therapeutics. A wide of anticancer molecules both from a pharmacological and physicochemical perspective have been developed as NS formulations by several groups including ours. Our objective in this review is to capture a systematic and comprehensive snapshot of the state‐of‐the‐art of NS‐aided cancer therapeutics reported so far. This review will provide an ideal platform for both the formulation scientists working on new polymeric/drug development and cancer biologists/scientists to understand the current nanotechnologies in CD‐based NS‐aided cancer therapeutics. The scope of the review is limited to small molecules and CD‐based NS. The review covers in detail the problems associated with anticancer small molecules, and the solution provided by CD‐based NS specifically for camptothecin, curcumin, paclitaxel, tamoxifen, resveratrol, quercetin, oxygen‐NS, temozolomide, doxorubicin, and 5‐Fluorouracil. WIREs Nanomed Nanobiotechnol 2016, 8:579–601. doi: 10.1002/wnan.1384

Camptothecin‐loaded β‐cyclodextrin nanosponge. (a) Camptothecin‐loaded β‐cyclodextrin nanosponge (CN‐CPT) provides a stable aqueous nanosuspension with low polydispersity index. (b) Transmission electron microscopy (TEM) images of CN‐CPT: TEM showed a spherical morphology and corroborated the particle size results. (Reprinted with permission from Ref . Copyright 2002 Elsevier B.V.)
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General applications of cyclodextrin nanosponge in cancer therapeutics presented in a schematic form.
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Schematic structure of cyclodextrin nanosponge. (Reprinted with permission from Ref . Copyright 2015 Wiley Periodicals, Inc. and the American Pharmacists Association)
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Nanosponge‐aided delivery for cancer therapeutics in a nutshell.
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Effect of quercetin nanosponge in: (a) DPPH radical‐scavenging activity, (b) antisuperoxide anion formation, (c) superoxide anion‐scavenging activity, (d) metal chelating activity. (Reprinted with permission from Ref . Copyright 2014 Springer Science+Business Media New York).
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Accumulation study of resveratrol and complex in rabbit mucosa. (Reprinted with permission from Ref . Copyright 2011 American Association of Pharmaceutical Scientists)
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Oral pharmacokinetic profiles of tamoxifen citrate and tamoxifen nanosponge formulations. (Reprinted with permission from Ref . Copyright 2013 Informa Healthcare USA, Inc.)
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Nanosponge‐vehiculated paclitaxel. Toxicity of paclitaxel‐loaded nanosponges dissolved in DMSO compared to plain paclitaxel at three different time points. **P = 0.01; ***P = 0.001. Significance against internal control as described in the text. (Reprinted with permission from Ref . Copyright 2012 Springer Science+Business Media B.V.)
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Absorption kinetics of paclitaxel. (Reprinted with permission from Ref . Copyright 2010 Informa UK Ltd)
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Inhibition of proliferation and clonogenicity following CPT and CN‐CPT treatment. (a) Effect of CPT and CN‐CPT on PC‐3 and DU145 cell lines proliferation was tested by MTT assay. Cells (800/well) were treated with increasing concentrations of CPT and CN‐CPT for 24–96 h and the result was expressed as absorbance at 570 nm. Values are expressed as mean ± SD; each group n = 8, experiments in triplicate. (b) Effect of CPT and CN‐CPT on PC‐3 and DU145 cell lines viability. Data were expressed as the percentage of cells viability versus control. One‐way ANOVA and the Dunnett's test revealed statistically significance differences (*p <0.05; **p *0.01) of CN‐CPT versus CPT treated cells. (c) Effect of CPT and CN‐CPT on prostate cancer cells clonogenicity was tested by colony forming assay. DU145 and PC‐3 cells (500/well) were seeded in six well plates and treated with both compounds at the indicated concentrations for 72 h. Cells were cultured for 10 days and subsequently fixed and stained with crystal violet. (Reprinted with permission from Ref . Copyright 2012 Elsevier B.V.)
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Plasma stability of the camptothecin (CAM) formulations: (a) Effect of various nanosponge on the stability of CAM complexes in PBS over a period of 24 h, (b) Plasma stability of CAM complexes over a period of 24 h. (Reprinted with permission from Ref . Copyright 2010 Elsevier B.V.)
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Mauro Ferrari

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started out in mechanical engineering and became interested in nanotechnology with his studies on nanomechanics and nanofluidics. His research work and involvement with setting up some of the premier nano centers and alliances in the world, bringing together universities, hospitals, and federal agencies, showcases interdisciplinarity at work.

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