Polyaspartamide<i>‐graft‐</i>Polymethacrylate Nanoparticles for Doxorubicin Delivery

Licciardi, Mariano; Cavallaro, Gennara; Stefano, Mauro Di; Fiorica, Calogero; Giammona, Gaetano

doi:10.1002/mabi.201000399

Cited by 17 publications

(20 citation statements)

References 24 publications

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“…The effectiveness of doxorubicin is impeded by acute and subacute side effects, mainly dose-limiting irreversible cardiotoxicity and myelosuppression (10). In an attempt to reduce the side-effects of doxorubicin and to improve its anticancer efficacy, various nanocarriers of doxorubicin and daunorubicin have been developed, including micelles, dendrimers, solid-lipid, and polymer nanoparticles (11)(12)(13)(14)(15). Liposomes are by far the most studied nanoformulation of doxorubicin, and are the only products that reached the market (Caelyx, Myocet).…”

mentioning

confidence: 99%

A unique squalenoylated and nonpegylated doxorubicin nanomedicine with systemic long-circulating properties and anticancer activity

Maksimenko

Dosio

Mougin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

189

163

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We identified that the chemical linkage of the anticancer drug doxorubicin onto squalene, a natural lipid precursor of the cholesterol's biosynthesis, led to the formation of squalenoyl doxorubicin (SQ-Dox) nanoassemblies of 130-nm mean diameter, with an original "loop-train" structure. This unique nanomedicine demonstrates: (i) high drug payload, (ii) decreased toxicity of the coupled anticancer compound, (iii) improved therapeutic response, (iv) use of biocompatible transporter material, and (v) ease of preparation, all criteria that are not combined in the currently available nanodrugs. Cell culture viability tests and apoptosis assays showed that SQ-Dox nanoassemblies displayed comparable antiproliferative and cytotoxic effects than the native doxorubicin because of the high activity of apoptotic mediators, such as caspase-3 and poly(ADPribose) polymerase. In vivo experiments have shown that the SQDox nanomedicine dramatically improved the anticancer efficacy, compared with free doxorubicin. Particularly, the M109 lung tumors that did not respond to doxorubicin treatment were found inhibited by 90% when treated with SQ-Dox nanoassemblies. SQ-Dox nanoassembly-treated MiaPaCa-2 pancreatic tumor xenografts in mice decreased by 95% compared with the tumors in the saline-treated mice, which was significantly higher than the 29% reduction achieved by native doxorubicin. Concerning toxicity, SQ-Dox nanoassemblies showed a fivefold higher maximum-tolerated dose than the free drug, and moreover, the cardiotoxicity study has evidenced that SQ-Dox nanoassemblies did not cause any myocardial lesions, such as those induced by the free doxorubicin treatment. Taken together, these findings demonstrate that SQ-Dox nanoassemblies make tumor cells more sensitive to doxorubicin and reduce the cardiac toxicity, thus providing a remarkable improvement in the drug's therapeutic index.squalene-doxorubicin bioconjugate | pancreatic cancer | lung cancer

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mentioning

confidence: 99%

A unique squalenoylated and nonpegylated doxorubicin nanomedicine with systemic long-circulating properties and anticancer activity

Maksimenko

Dosio

Mougin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

189

163

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“…PHEA is a biocompatible synthetic polymer, soluble in water, with a similar structure to human amino acids. The use of PHEA as carriers of drugs and as a starting material for many other biomedical and pharmaceutical applications has already been reported [29,30]. PHEA was linked with polylactic acid (PLA) and subsequently electrospun in a mixture with polycaprolactone (PCL) [31,32].…”

Section: Methodsmentioning

confidence: 99%

Electrospun PHEA-PLA/PCL Scaffold for Vascular Regeneration: A Preliminary in Vivo Evaluation

Buscemi

Palumbo

Maffongelli

et al. 2017

Transplantation Proceedings

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Background. There is increasing interest in the development of vessel substitutes, and many studies are currently focusing on the development of biodegradable scaffolds capable of fostering vascular regeneration. We tested a new biocompatible and biodegradable material with mechanical properties similar to those of blood vessels.Methods. The material used comprises a mixture of a,b-poly(N-2-hydroxyethyl)-D,L-aspartamide (PHEA) and polylactic acid (PLA), combined with polycaprolactone (PCL) by means of electrospinning technique. Low-molecular-weight heparin was also linked to the copolymer. A tubular PHEA-PLA/PCL sample was used to create an arteriovenous fistula in a pig model with the use of the external iliac vessels. The flow was assessed by means of Doppler ultrasound examination weekly, and 1 month after the implantation we removed the scaffold for histopathologic evaluation. Results. The implants showed a perfect leak-proof seal and adequate elastic tension to blood pressure. About w3 weeks after the implantation, Doppler examination revealed thrombosis of the graft, so we proceeded to its removal. Histologic examination showed chronic inflammation, with the presence of foreign body cells and marked neovascularization. The material had been largely absorbed, leaving some isolated spot residues. Conclusions. The biocompatibility of PHEA-PLA/PCL and its physical properties make it suitable for the replacement of vessels. In the future, the possibility of functionalizing the material with a variety of molecules, to modulate the inflammatory and coagulative responses, will allow obtaining devices suitable for the replacement of native vessels.

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“…which is a technique used for the first time by Coessens, et al [8] that allow to overcome most of the typical problems of the common grafting procedures (especially the control of the grade of functionalization, and the polydispersity of the obtained products). Nanoparticles for the pH sensitive delivery of doxorubicine were producted by ATRP of sodium methacrylate onto the polymeric backbone of (PHEA), a synthetic polymer soluble both in organic solvents and in water [9]. In this case the chemical versatility of PHEA has made possible the insertion in the macromolecule of several chemical groups able to trigger ATRP process in a way to obtain a copolymer through a "growing from" process.…”

Section: Important Chemical Modifications Have Been Recently Made Posmentioning

confidence: 99%

Biocompatible Polymers and Processing Techniques in Drug Delivery and Tissue Engineering

Giamonna¹,

Fiorica²,

Palumbo³

et al. 2013

Journal of Pharmaceutics and Drug Development

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Polyaspartamide‐graft‐Polymethacrylate Nanoparticles for Doxorubicin Delivery

Cited by 17 publications

References 24 publications

A unique squalenoylated and nonpegylated doxorubicin nanomedicine with systemic long-circulating properties and anticancer activity

A unique squalenoylated and nonpegylated doxorubicin nanomedicine with systemic long-circulating properties and anticancer activity

Electrospun PHEA-PLA/PCL Scaffold for Vascular Regeneration: A Preliminary in Vivo Evaluation

Biocompatible Polymers and Processing Techniques in Drug Delivery and Tissue Engineering

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