A Novel Nanocarrier System for Cancer Treatment

Author(s): María Teresa Corona-Ortega, Ramón Soto-Vázquez, Rosalva Rangel-Corona, Rosa María Huante-García, Leonor Aguilar-Santelises, Araceli García del Valle, Benny Weiss-Steider.

Journal Name: Current Nanomedicine

Volume 6 , Issue 2 , 2016

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Abstract:

Background: We have designed and patented a novel nanocarrier system to specifically deliver IL-2 to tumor cells expressing the IL-2 receptor (IL-2R). In this work, we provide data of the physical characteristics of the system, such as size, complexity and viscosity, stability to light, pH and temperature, pharmacodynamic and pharmacokinetic parameters, as well as toxic and antitumor properties. The nanocarrier system consists of positively charged liposomes that present non-covalently bound IL-2 molecules on their external surface to facilitate recognition by IL-2R expressing cells.

Methods: We used transmission electron microscopy and flow cytometry to evaluate physical characteristics of the system and immunodeppressed CBA mice for toxicological, pharmacodynamic and pharmacokinetic parameters.

Results: Our results show that liposomes in our system have a unilamellar structure, small enough to be easily internalized by tumor cells, a viscosity similar to water, and are stable over a wide range of light, pH and temperature conditions, which provide them with convenient properties for pharmaceutical dosage forms, and storage stability. By using an animal model of immunodeppressed CBA mice induced to form tumors derived from cervical cancer human cells, we show that our liposomes are non-toxic even at very high doses of liposome bound IL-2 molecules, and that far lower doses are very effective in significantly reducing the tumor burden. Our system has the same antitumor effect than free IL-2, but in the absence of extremely high toxicity associated with this molecule when administrated systemically, and at a longer permanence in tissues.

Conclusion: Our results shows that our system has low toxicity, long tissue permanence, and high antitumor activity, thus we propose the possibility that our IL-2 nanocarrier system could be useful for anti-cancer therapy when tumor cells express the IL-2R.

Keywords: IL-2 and IL-2R, liposomes, nanocarrier system, pharmacokinetic and pharmacodynamic properties, toxicity, antitumor activity.

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2016
Page: [133 - 145]
Pages: 13
DOI: 10.2174/2468187306999160427114000

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