New chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) as doxorubicin carriers

Gardikis, Κonstantinos; Tsimplouli, Chrisiida; Dimas, Konstantinos; Micha-Screttas, Maria; Demetzos, Costas

doi:10.1016/j.ijpharm.2010.10.007

Cited by 54 publications

(25 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, there is a consensus in the drug-delivery community that new concepts are needed for the construction of long-circulating nanocarriers avoiding the use of PEG. Another concern is the low drug-loading (i.e., milligrams of the anticancer anthracycline per milligrams of carrier material), though the use of tansmembrane pH gradient-loading methods into liposomes varies from 0.05 μM/1 μM lipid to 0.21 μM/1 μM lipid (25,26). With polymer nanoparticles, the maximum payload is generally less than 10% (wt/wt) (27).…”

Section: Significancementioning

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

View full text Add to dashboard Cite

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

show abstract

Section: Significancementioning

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

View full text Add to dashboard Cite

show abstract

“…A modulatory liposomal controlled release system (MLCRS) combined liposomal and dendrimeric technologies incorporating the anticancer drug doxorubicin has been recently reported (Papagiannaros et al, 2005) while dendrimers locked-into liposomal formulation (D locked-in L) is a new term in the drug delivery (Tekade et al, 2009;Gardikis et al, 2010a) and considered as a class of MLCRSs. We followed the concept of using acronyms, in order to reach to a specific description of modulatory controlled release nanosystems (MCRnSs).…”

Section: Advanced Drug Delivery Nanosystems and A Proposal To Their Cmentioning

confidence: 99%

“…Preclinical studies have shown that aDDnSs can interfere with the pharmacokinetic profile of the incorporated bioactive molecule and, consequently, alter its absorption, biodistribution, metabolism and excretion profile (Gardikis et al, 2010a(Gardikis et al, ,b, 2011Kontogiannopoulos et al, 2012). aDDnSs can be characterized as mixed nanosystems due to the combination of different in nature bionanomaterials and are used for biomimetic delivery (Balmert & Little, 2012).…”

Section: Advanced Drug Delivery Nanosystems and A Proposal To Their Cmentioning

confidence: 99%

“…The classification of drug delivery nanosystems. Yang et al (2012) Chi-aDDnSs (targeted nanospheres and pretargeted radioimmunotherapy) Paclitaxel Polymers (ABA-type copolymers, PEG) Bushman et al (2013) Chi-aDDnSs Indomethacin Lipids/Gradient block copolymers Pippa et al (2013b) containing copolymers from poly(isoprene-b-ethylene oxide) diblock copolymers as well as the molecular characteristics of the -lactam functionalized block copolymers was recently published (Gardikis et al, 2010a). Because of the great interest in drug delivery, carriers composed of new biomaterials like block co-polymers or new synthetic dendrimers (i.e.…”

Section: Final Characterization F(chi-) or (Hy-)-amcddnssmentioning

confidence: 99%

See 1 more Smart Citation

Advanced drug delivery nanosystems (aDDnSs): a mini-review

Demetzos¹,

Pippa²

2013

Drug Delivery

Self Cite

View full text Add to dashboard Cite

Significant progress has been made in nanoscale drugs and delivery systems employing diverse chemical formulations to facilitate the rate of drug delivery and to improve its pharmacokinetics. Biocompatible nanomaterials have been used as biological markers, contrast agents for imaging, healthcare products, pharmaceuticals, drug-delivery systems as well as in detection, diagnosis and treatment of various types of diseases. The classification of drug delivery nanosystems (DDnSs) is a crucial issue and fundamental efforts on this subject are missing from the literature. This article deals with the classification of DDnSs with a modulatory controlled release profile (MCR) denoted as modulatory controlled release nanosystems (MCRnSs). Conventional (c) and advanced (a) DDnSs are denoted by the acronyms cDDnSs and aDDnSs, and can be composed of a single or more than one biomaterials, respectively. The classification was based on their characteristics such as: surface functionality (f), the nature of biomaterials used and the kind of interactions between biomaterials. The aDDnSs can be classified as hybridic (Hy-) or chimeric (Chi-) based on the nature -same or different respectively -of biomaterials and inorganic materials used. The nature of the elements used for producing advanced biomaterials is of great importance and medicinal chemistry contributes effectively to the production of aDDnSs.

show abstract

“…Release nano Systems (MCRnSs) are considered as drug delivery systems that can modulate the release of the encapsulated bioactive compound (Gardikis et al, 2010(Gardikis et al, , 2011Pippa et al, 2013a,b,c,d). The nature of the elements used for producing advanced biomaterials are of great importance and medicinal chemistry and new synthetic bioelements (i.e.…”

Section: Modulatory Controlled Release Profile (Mcr) Denoted As Modulmentioning

confidence: 99%

Advanced nanocarriers for an antitumor peptide

Pippa

Pispas

Demetzos³

et al. 2013

J Nanopart Res

Self Cite

View full text Add to dashboard Cite

In this work, tigapotide (PCK3145) was incorporated into novel nanocarriers based on polymeric, lipidic and dendrimeric components, in order to maximize the advantages of the drug delivery process and possibly its biological properties. PCK3145 was incorporated into lipidic nanocarriers composed of Eggphosphatidylcholine (EggPC and finally into dendrimeric structures (i.e. PAMAM G4) . Light scattering techniques are used in order to examine the size, the size distribution and the z-potential of the nanocarriers in aqueous and biological media. Fluorescence spectroscopy was utilized in an attempt to extract information on the internal nanostructure and microenvironment of polyelectrolyte/PCK3145 aggregates. Therefore, these studies could be a rational roadmap for producing various effective nanocarriers in order to ameliorate the pharmacokinetic behavior and safety issues of antitumor and anticancer biomolecules.

show abstract

New chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) as doxorubicin carriers

Cited by 54 publications

References 30 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

Advanced drug delivery nanosystems (aDDnSs): a mini-review

Advanced nanocarriers for an antitumor peptide

Contact Info

Product

Resources

About