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.