Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer

Borrajo, Erea; Abellan-Pose, Raquel; Soto, Atenea; García-Fuentes, Marcos; Csaba, Nœmi; Alonso, Marı́a José; Vidal, Anxo

doi:10.1016/j.jconrel.2016.07.048

Cited by 34 publications

(23 citation statements)

References 46 publications

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“…To enhance the oral bioavailability and efficacy of DTX, numerous strategies have been reported such as nano-sized carriers i.e. polymeric Nps [26,27], self-microemulsifying drug delivery systems [28], solid self-emulsifying drug delivery systems [29], microemulsions [30] and nanocapsules [31]. Furthermore, a different model, i.e.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

Ahmad

Alam

Naqvi

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

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Docetaxel (DTX), a cytotoxic taxane, is a poor water-soluble drug and exhibits less oral bioavailability. Current research investigates the effective transport, for DTX-loaded chitosan (CS)-coated-poly-lactide-co-glycolide (PLGA)-nanoparticles (NPs) (DTX-CS-PLGA-NPs) and DTX-PLGA-NPs as well as a novel third-generation P-gp inhibitor i.e. GF120918 (Elacridar), across intestinal epithelium with its successive uptake by the tumour cells in an in vitro model. The prepared NPs showed a spherical shape particle size i.e. <123.96 nm with polydispersity index (PDI) of <0.290 whereas for CS-coated NPs, the zeta potential was converted from negative to positive value along with a small modification in particle size distribution. The entrapment efficiency observed for DTX-CS-PLGA-NPs was 74.77%, whereas the in vitro release profile revealed an initial rapid DTX release followed by a sustained release pattern. For apparent permeability, DTX-CS-PLGA-NPs and DTX-PLGA-NPs along with GF120918 showed a five-fold (p < .01) and 2.2-fold enhancement, respectively, as observed in rat ileum permeation study. Similarly, for pharmacokinetic (PK) studies, higher oral bioavailability was observed from DTX-CS-PLGA-NPs (5.11-folds) and DTX-PLGA-NPs (3.29-folds) as compared with DTX-suspension (DTX-S). Cell uptake studies on A549 cells as performed for DTX-CS-PLGA-NPs and DTX-PLGA-NPs loaded with rhodamine 123 dye, exhibited enhanced uptake as compared with plain dye solution. The enhanced uptake for DTX-CS-PLGA-NPs and DTX-PLGA-NPs formulations in the presence of GF120918 was confirmed further with the help of confocal laser scanning microscopic images (CLSM). The potential of the third-generation novel P-gp inhibitor (GF120918) investigated for the effective delivery of DTX as well as investigation of permeability and uptake studies whereby a strong potential of GF120918 for effective oral delivery was established.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

Ahmad

Alam

Naqvi

et al. 2017

Artificial Cells, Nanomedicine, and Biotechnology

View full text Add to dashboard Cite

show abstract

“…Docetaxel (DTX) is a broad-spectrum chemotherapeutic drug that possesses strong activity against many human cancers, such as metastatic breast, lung, prostate and ovarian cancers, through its binding to β-tubulin and stabilizing microtubules, thus leading to cell cycle arrest and cell apoptosis15. However, the clinical application of DTX is greatly limited by its poor water-solubility, rapid clearance rate, adverse side effects, poor tumor penetration and the occurrence of drug resistance1617. In the marketed formulations, Taxotere ® and Duopafei ® , high concentration of Tween 80 and ethanol has to be added to improve drug solubility, therefore resulting in adverse side effects including acute hypersensitivity, fluid retention, neurotoxicity and febrile neutropenia18.…”

mentioning

confidence: 99%

Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer

Zhang

Yang

et al. 2017

Sci Rep

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Co-delivery of microRNAs and chemotherapeutic drugs into tumor cells is an attractive strategy for synergetic breast cancer therapy due to their complementary mechanisms. In this work, a core-shell nanocarrier coated by cationic albumin was developed to simultaneously deliver miRNA-34a and docetaxel (DTX) into breast cancer cells for improved therapeutic effect. The co-delivery nanocarriers showed a spherical morphology with an average particle size of 183.9 nm, and they efficiently protected miRNA-34a from degradation by RNase and serum. Importantly, the nanocarriers entered the cytosol via a caveolae-mediated pathway without entrapment in endosomes/lysosomes, thus improving the utilization of the cargo. In vitro, the co-delivery nanocarriers suppressed the expression of anti-apoptosis gene Bcl-2 at both transcription and protein levels, inhibited tumor cell migration and efficiently induced cell apoptosis and cytotoxicity. In vivo, the co-delivery nanocarriers prolonged the blood circulation of DTX, enhanced tumor accumulation of the cargo and significantly inhibited tumor growth and metastasis in 4T1-tumor bearing mice models. Taken together, the present nanocarrier co-loading with DTX and miRNA-34a is a new nanoplatform for the combination of insoluble drugs and gene/protein drugs and provides a promising strategy for the treatment of metastatic breast cancer.

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“…However, our lab has expanded this technology to allow NCs to carry hydrosoluble macromolecules, such as proteins, peptides, and polynucleotides, using them in different therapeutic areas. For example, in the oncology field, we have developed different polymeric NCs containing the cytotoxic drugs plitidepsin and docetaxel, which were able to prolong the blood circulation time of these drugs and reduce their toxicity. In addition, an important accumulation of the drugs in the lymphatic system was observed.…”

Section: Introductionmentioning

confidence: 99%

Engineering, on‐demand manufacturing, and scaling‐up of polymeric nanocapsules

Crecente‐Campo

Alonso

2018

Bioengineering & Transla Med

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Polymeric nanocapsules are versatile delivery systems with the capacity to load lipophilic drugs in their oily nucleus and hydrophilic drugs in their polymeric shell. The objective of this work was to expand the technological possibilities to prepare customized nanocapsules. First, we adapted the solvent displacement technique to modulate the particle size of the resulting nanocapsules in the 50–500 nm range. We also produced nanosystems with a shell made of one or multiple polymer layers i.e. chitosan, dextran sulphate, hyaluronate, chondroitin sulphate, and alginate. In addition, we identified the conditions to translate the process into a miniaturized high‐throughput tailor‐made fabrication that enables massive screening of formulations. Finally, the production of the nanocapsules was scaled‐up both in a batch production, and also using microfluidics. The versatility of the properties of these nanocapsules and their fabrication technologies is expected to propel their advance from bench to clinic.

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Docetaxel-loaded polyglutamic acid-PEG nanocapsules for the treatment of metastatic cancer

Cited by 34 publications

References 46 publications

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

RETRACTED ARTICLE: Preparation and characterization of surface-modified PLGA-polymeric nanoparticles used to target treatment of intestinal cancer

Cytosolic co-delivery of miRNA-34a and docetaxel with core-shell nanocarriers via caveolae-mediated pathway for the treatment of metastatic breast cancer

Engineering, on‐demand manufacturing, and scaling‐up of polymeric nanocapsules

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