The Use of Liposomes and Nanoparticles as Drug Delivery Systems to Improve Cancer Treatment in Dogs and Cats

Abstract

Background: Cancer remains a leading cause of death in companion animals. In human medicine, liposomes and nanoparticles have been extensively investigated as drug delivery systems (DDS) for anticancer agents due to their ability to target cancerous cells and reduce the negative side effects of free cytostatic drugs. In this review, the authors discuss the results of clinical trials using liposomes and polymer-based nanoparticles as DDS to improve cancer treatment in dogs and cats, indicating which ones seem worth further evaluation. The authors then overview ongoing animal cancer clinical trials, evaluating nano-DDS registered on the American Veterinary Medical Association Animal Health Studies Database. Finally, the authors indicate the nano-drugs that require further in vivo evaluation based on the encouraging results obtained from in vitro studies. Conclusions: Liposomes have been the most investigated nano-DDS in veterinary medicine. The lack of cardiotoxicity of the commercially available liposomal doxorubicin (Doxil/Caelyx) suggests it should be used in dogs with cardiac disorders, rather than using free doxorubicin. Cisplatin-incorporated hyaluronic acid nanoparticles, nanocrystals of cisplatin, and paclitaxel are the most promising nano-drugs for potent applications in treating various canine cancers (e.g. oral melanoma, oral sarcoma, and anal gland adenocarcinoma) and their translation into the treatment of human diseases.

Liposomes; from synthesis to targeting macrophages

“…This PEGylation of liposomes has been shown to work in a study on cancer treatment in dogs and cats. In this study, it was seen that these liposomes with doxorubicin worked at reducing tumors in cats [6]. Another study shows that doxorubicin loaded onto phosphatidyldiglycerol thermosensitive liposomes worked as a treatment for soft tissue sarcoma in cats as well [14].…”

“…Another important consideration is how to make the liposomes last longer in the body. Such a modification to improve and protect the liposome is the addition of polyethylene glycol (PEG) [6,9,10]. These PEGylated liposomes have a protective hydrophilic layer so that liposomes can better enter areas of the body such as the reticuloendothelial system [9,[11][12][13].…”

“…Along with aqueous solutions, liposomes are popular because they can also load lipophilic drugs due to the amphipathic nature of their bilayer membranes. Besides for their drug loading ability, liposomes are chosen as an area of study because of their biocompatibility, but they are also biodegradable and present a low toxicity [5,6]. While the structure of liposomes can be specialized beyond this basic structure, they can be classified more rigidly by size and type.…”

Ferritin Nanocages for Protein Delivery to Tumor Cells

“…From a very general point of view, drug delivery systems (DDS) are nanocarriers composed of lipids and/or polymers and their associated therapeutics. Over the years, several nanocarriers have been developed, including liposomes [16,17]; solid lipid nanoparticles (Compritol ® 888 ATO, Precirol ® A common feature of all ferritins is that each subunit consists of a characteristic four-helical bundle (helices A-D), plus a fifth short helix E (not present in Dps proteins) pointing inside the protein cavity. Ferritin nanocages are able to self-assemble in a tetraeicosamer protein shell, and the dimers are the first intermediate in this pathway [50].…”

Lipidated poly(amino acid) nanostructures as versatile therapeutic delivery vehicles

“…In choosing which nanoparticle system to use, material composition must be suitable for the intended application, with degradation mechanism and kinetics appropriate for the desired biological destination. While many materials have been studied, polymers are attractive as they can be made from a variety of chemistries with varying degradation mechanisms including commonly used ones like poly(lactide-co-glyocolide), hyaluronan, poly(dopamine), and poly(aspartic acid) 18–21 .…”