TOPICAL SYSTEM OF CONTROLLED RELEASE OF NANOPARTICLES LOADED WITH ANTITUMORAL DRUGS

GARRO CINTIA; LEAL ALDO; CORREA N. MARIANO; STAGNOLI A. SOLEDAD; NIEBYLSKI ANA; BOCCACCINI, ALDO R; ERTEKIN OZLEM; SORIA GASTÓN

Salta

Congreso; Joint LV Annual SAIB Meeting and XIV PABMB Congress; 2019

Two of the main setbacks of many chemotherapeutical drugs are their widespread systemic distribution and limited permeability across the cell membrane. In fact, to reach effective concentrations of the drugs at tumor sites, it is usually necessary to administer relatively high doses of drugs which ultimately lead to severe side effects. In this work, our goal was to develop a new system capable of stably encapsulate drugs that target tumor cells with controlled release of chemotherapeutic drugs. Moreover, we aimed to design a system that can be used on patients in a topical way. Topical drug delivery eliminates the need for systemic drug administration and offers a less invasive alternative than conventional therapy. Nanocarriers could be used to improve solubility, cellular delivery, distribution in vivo, control release and decrease the toxicity of antitumoral drugs. In the present study, we used the biocompatible materials DOPC (D) and BHD-AOT (B) as nanocarriers capable of stably encapsulating antitumor drugs, such as Curcumin (C). C is a polyphenolic natural compound with well-known antitumoral, antioxidant and anti-inflammatory properties. However, the therapeutic efficacy of C is limited due to its poor aqueous solubility and its difficulty to cross the cell membrane. In this study, the in vitro biocompatibility of vesicles and the ability to encapsulate C of B (BC) and D (DC) was evaluated. The cellular interaction and antitumor activity of BC and DC were studied by nano-zetasizer and flow cytometry. Finally, to perform a local and controlled release of BC and DC we use a new type of hydrogel (oxidized alginate co-polymerized with gelatin) as a support matrix. This assay was carried out using rat skin by Franz diffusion cell and fluorescence spectroscopy. Our results showed that B and D are highly efficient to encapsulate C and interact with tumor cells. D was harmless in a wider range of concentrations compared to B (concentrations lower than 0.05 mg/ml). DC was more efficient than BC, because it was able to deliver the high concentrations of C necessary to reach its antitumoral activity. Another important finding was that the incorporation of DC in tumor cells was greater (≥70%) than in non-tumoral cell lines (≤10%). The hydrogel incorporated and protected BC and DC efficiently, after lyophilization and in humid conditions both at low and physiological temperatures. Finally, after the controlled degradation of the hydrogel, both BC and DC vesicles crossed the stratum corneum without morphological alterations and without losing the encapsulated drug. Together, our results suggest that this type of vesicles can become ideal systems for the delivery of antitumor drugs in minimally invasive topical applications.