New Drug Delivery Nanosystem Combining Liposomal and Dendrimeric Technology (Liposomal Locked-In Dendrimers) for Cancer Therapy

Gardikis, Κonstantinos; Hatziantoniou, Sophia; Bucoş, Madalina; Fessas, Dimitrios; Signorelli, Marco; Felekis, Theodoros; Zervou, Maria; Screttas, Constantinos G.; Steele, Barry R.; Йонов, Максим; Micha-Screttas, Maria; Klajnert, Barbara; Bryszewska, Maria; Demetzos, Costas

doi:10.1002/jps.22121

Cited by 51 publications

(48 citation statements)

References 43 publications

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“…The size of the liposomes affects their residence time in the systemic blood circulation, as well as their pathways within the body. The smaller the size, the more difficult it is for them to become detectable by the macrophages of the immune system, increasing in this way the residence time in the systemic circulation, as well as their effectiveness [35,36].…”

Section: Liposome Characterizationmentioning

confidence: 99%

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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Abstract:Liposomes are considered to be one of the most successful drug delivery systems.They apply nanotechnology to potentiate the therapeutic efficacy and reduce the toxicity of conventional medicines. Shikonin and alkannin, a pair of chiral natural naphthoquinone compounds, derived from Alkanna and Lithospermum species, are widely used due to their various pharmacological activities, mainly wound healing, antioxidant, anti-inflammatory and their recently established antitumor activity. The purpose of this study was to prepare conventional and PEGylated shikonin-loaded liposomal formulations and measure the effects of different lipids and polyethylene glycol (PEG) on parameters related to particle size distribution, the polydispersity index, the zeta potential, drug-loading efficiency and the stability of the prepared formulations. Three types of lipids were assessed (1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-Distearoyl-sn-glycero-3-phosphocholine (DSPC) and 1,2-distearoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DSPG)), separately and in mixtures, forming anionic liposomes with good physicochemical characteristics, high entrapment efficiencies (varying from 56.5 to 89.4%), satisfactory in vitro release profiles and good physical stability. The addition of the negatively charged DSPG lipids to DOPC, led to an increment in the drug's incorporation efficiency and reduced the particle size distribution. Furthermore, the shikonin-loaded PEGylated sample with DOPC/DSPG, demonstrated the most satisfactory characteristics. These findings are considered promising and could be used for further design and improvement of such formulations.

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Section: Liposome Characterizationmentioning

confidence: 99%

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Tsermentseli

Kontogiannopoulos

Papageorgiou

et al. 2018

Fluids

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“…However, its clinical application is limited by cardiac hypertrophy, a dose-limiting side effect arising from the formation of free-radicals and lipid peroxidation (32). The design of doxorubicin-loaded nanocarriers (i.e., liposomes or nanoparticles) has gained increasing interest as a mean of improving the treatment of neoplastic diseases and reducing the drug-mediated cardiotoxicity (16,(33)(34)(35). However, the need to surface-functionalize these nanodevices with PEG raises toxicological issues because of the previously mentioned biodegradability and safety concerns of PEG (23,36).…”

Section: E)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.

184

159

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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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“…They also offer other potential advantages such as prolongation of drug circulation time, protection of a drug from its surroundings, increase in drug stability (and possibly effectiveness) and the ability to target diseased tissue (Gardikis et al, 2010d). There are two well-known strategies for the dendrimers' synthesis; the divergent strategy introduced by Vogtle, Tomalia and Newkome and the convergent synthetic path introduced by Hawker and Frechet (Villalonga-Barber et al, 2008).…”

Section: Drug Delivery Systemsmentioning

confidence: 99%

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

Demetzos¹,

Pippa²

2013

Drug Delivery

Self Cite

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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.

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New Drug Delivery Nanosystem Combining Liposomal and Dendrimeric Technology (Liposomal Locked-In Dendrimers) for Cancer Therapy

Cited by 51 publications

References 43 publications

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

Comparative Study of PEGylated and Conventional Liposomes as Carriers for Shikonin

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

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

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