In Vitro and In Vivo Evaluation of desmopressin-loaded poly( D,L -lactic-co-glycolic acid) Nanoparticles for Its Potential Use in Cancer Treatment

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Abstract
Aim: To develop and characterize the antitumor activity of poly(D,L-lactic-co-glycolic acid) nanoparticles loaded with hemostatic and anticancer drug desmopressin (dDAVP). Materials & methods: After full physicochemical characterization, anticancer activity of dDAVP-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles (NPdDAVP) was evaluated in vitro and in vivo on a highly aggressive breast cancer model. Results: After efficiently loading desmopressin in poly(D,L-lactic-co-glycolic acid) matrix, NPdDAVP exhibited suitable physicochemical characteristics for biomedical applications. NPdDAVP displayed a potent cytostatic effect in vitro, inhibiting tumor cell proliferation and colony forming ability. Moreover, intravenous treatment using nanoparticulated-dDAVP inhibited tumor progression and prolonged survival in animals bearing rapidly-growing mammary tumors. Conclusion: Within the framework of promising dDAVP repurposing studies, these findings support further preclinical development of the NPdDAVP for the management of highly aggressive cancer. Lay abstract Desmopressin (dDAVP) is a hemostatic drug recently repurposed for its use in oncology. In this setting, polymeric biodegradable nanocarriers are proposed as interesting alternatives to deliver dDAVP, helping to overcome inherent limitations of peptide drugs such as short in vivo instability and reduced permanence in the tumor milieu. As a result, dDAVP-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles were developed for its potential use in cancer management. Besides exhibiting suitable physicochemical properties for biomedical use, dDAVP-loaded poly(D,L-lactic-co-glycolic acid) nanoparticles were capable of hampering cancer cell growth and disease progression, as well as extending survival in animals bearing highly aggressive tumors. Results support further preclinical development.

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