Novel polyurea/polyurethane nanocapsules loaded with a tambjamine analog to improve cancer chemotherapy delivery and safety in lung cancer

Abstract

Abstract Background The clinical potential of many promising anti-tumor drugs is restricted by their intrinsic physicochemical properties and lack of selectivity towards cancer cells, leading to insufficient drug concentration at the tumor site. To overcome these hurdles, we have developed a new drug delivery system based on polyurea/polyurethane nanocapsules (NCs), which might protect the loaded drug from premature degradation and specifically release it inside cancer cells. Polyurea/polyurethane polymers present amphoteric properties, thus, these NCs are anionic at basic pH and cationic at acid pH. Tumor microenvironment is slightly acidic (6.8-7) in comparison to healthy tissue (7.2-7.4); hence, NCs became cationic in the tumor area, what facilitates their internalization into tumor cells. Methods In order to study this novel delivery system, an analog of tambjamine has been loaded in these amphoteric NCs and their selectivity and antitumor properties have been analyzed in vitro comparing two pHs, one acidic (6.8) and another basic (7.5) by proliferation assays, flow cytometry and microscopy. Additionally, the toxicity and efficacy of this delivery approach has been evaluated in an orthotopic lung cancer mouse model. Results In vitro results showed higher levels of NCs uptake in tumor cells at pH 6.8, resulting in greater cytotoxic effects compared to those at pH 7.5. Toxicity studies in vivo showed a good tolerability to repeated administrations and furthermore, the encapsulation of the drug reduces its toxicity compared to the free compound, allowing its intravenously administration. Preliminary data show a tendency limiting tumor growth, suggesting that NCs have reached the tumor site and the drug has been released. Conclusions Altogether, we have developed a promising new drug delivery system based on polyurea/polyurethane nanocapsules loaded with a tambjamine analog in order to be specifically delivered in cancer cells through reductive conditions, facilitating drug transport to tumor, administration and improving drug safety. Legal entity responsible for the study Universitat de Barcelona. Funding This work was partially supported by a grant from the Spanish government and the EU (PI18/00441). Disclosure C. Cusco: Full / Part-time employment, Not currently employed at Ecopoltech. J. Bonelli: Full / Part-time employment: Ecopoltech. J. Rocas: Leadership role, Officer / Board of Directors: Ecopoltech. All other authors have declared no conflicts of interest.