Background: Cancer is a common disease in dogs, with a growing incidence related to the age of the animal. Nanotechnology is being employed in the veterinary field in the same manner as in human therapy. Aim: This review focuses on the application of biocompatible nanocarriers for the treatment of canine cancer, paying attention to the experimental studies performed on dogs with spontaneously occurring cancer. Methods: The most important experimental investigations based on the use of lipid and non-lipid nanosystems proposed for the treatment of canine cancer, such as liposomes and polymeric nanoparticles containing doxorubicin, paclitaxel and cisplatin, are described and their in vivo fate and antitumor features discussed. Conclusions: Dogs affected by spontaneous cancers are useful models for evaluating the efficacy of drug delivery systems containing antitumor compounds.

The manuscript describes the development of zein nanoparticles containing paclitaxel (PTX) and the bromo-and extra-terminal domain inhibitor (S)-tertbutyl2-(4-(4-chlorophenyl)-2,3,9-trimethyl-6H-thieno(3,2-f)(1,2,4)triazolo(4,3-a)(1,4)diazepin-6-yl)acetate (JQ1) together with their cytotoxicity on triple-negative breast cancer cells. The rationale of this association is that of exploiting different types of cancer cells as targets in order to obtain increased pharmacological activity with respect to that exerted by the single agents. Zein, a protein found in the endosperm of corn, was used as a biomaterial to obtain multidrug carriers characterized by mean sizes of ˂200 nm, a low polydispersity index (0.1–0.2) and a negative surface charge. An entrapment efficiency of ~35% of both the drugs was obtained when 0.3 mg/mL of the active compounds were used during the nanoprecipitation procedure. No adverse phenomena such as sedimentation, macro-aggregation or flocculation occurred when the nanosystems were heated to 37 °C. The multidrug nanoformulation demonstrated significant in vitro cytototoxic activity against MDA-MB-157 and MDA-MB-231 cancer cells by MTT-test and adhesion assay which was stronger than that of the compounds encapsulated as single agents. The results evidence the potential application of zein nanoparticles containing PTX and JQ1 as a novel nanomedicine.

Doxorubicin hydrochloride (DOX) is a well-known antitumor drug used as first line treatment for many types of malignancies. Despite its clinical relevance, the administration of the compound is negatively affected by dose-dependent off-target toxicity phenomena. Nanotechnology has helped to overcome these important limitations by improving the therapeutic index of the bioactive and promoting the translation of novel nanomedicines into clinical practice. Herein, nanoparticles made up of wheat gliadin and stabilized by polyoxyethylene (2) oleyl ether were investigated for the first time as carriers of DOX. The encapsulation of the compound did not significantly affect the physico-chemical features of the gliadin nanoparticles (GNPs), which evidenced a mean diameter of ~180 nm, a polydispersity index < 0.2 and a negative surface charge. The nanosystems demonstrated great stability regarding temperature (25–50 °C) and were able to retain high amounts of drug, allowing its prolonged and sustained release for up to a week. In vitro viability assay performed against breast cancer cells demonstrated that the nanoencapsulation of DOX modulated the cytotoxicity of the bioactive as a function of the incubation time with respect to the free form of the drug. The results demonstrate the potential use of GNPs as carriers of hydrophilic antitumor compounds.

A biodegradable and biocompatible polymeric matrix made up of poly(d,l-lactide-co-glycolide) (PLGA) was used for the simultaneous delivery of rutin and the (S)-N-(2-oxo-3-oxetanyl)biphenyl-4-carboxamide derivative (URB894). The goal was to exploit the well-known radical scavenging properties of rutin and the antioxidant features recently reported for the molecules belonging to the class of N-acylethanolamine-hydrolyzing acid amidase (NAAA) inhibitors, such as URB894. The use of the compounds, both as single agents or in association promoted the development of negatively-charged nanosystems characterized by a narrow size distribution and an average diameter of ~200 nm when 0.2–0.6 mg/mL of rutin or URB894 were used. The obtained multidrug carriers evidenced an entrapment efficiency of ~50% and 40% when 0.4 and 0.6 mg/mL of rutin and URB894 were associated during the sample preparation, respectively. The multidrug formulation evidenced an improved in vitro dose-dependent protective effect against H₂O₂-related oxidative stress with respect to that of the nanosystems containing the active compounds as a single agent, confirming the rationale of using the co-encapsulation approach to obtain a novel antioxidant nanomedicine.