Table 1.

Preclinical and clinical trials on the use of liposomes and nanoparticles as drug delivery systems (DDS) in dogs and cats.

DDS	Active Substance/Market Name	Species	Type of Study	Results	Reference
‘Stealth’ PEGylated liposomes	doxorubicin/Doxil	dog	toxicity and efficacy	maximal tolerated dose: 1 mg/kg IV every 3 weeks; the dose-limiting toxicity: cutaneous toxicity resembling palmar-plantar erythrodysesthesia, lack of significant neutropenia or cardiomyopathy; an overall response rate was 25.5% (5 of 51 dogs had complete responses and 8 of 51 dogs had partial responses)	[20]
‘Stealth’ PEGylated liposomes	doxorubicin/Doxil	dog	randomized, efficacy and toxicity	no differences in survival time between dogs with splenic haemangiosarcoma after splenectomy treated with Doxil and free Dox as an adjuvant monotherapy; adverse side effects: a desquamating dermatitis like palmar-plantar erythrodysesthesia, anaphylactic reaction; lack of cardiotoxicity	[19]
‘Stealth’ PEGylated liposomes	doxorubicin/Doxil	dog	prospective, unmasked, uncontrolled toxicity, pharmacokinetic, efficacy	intraperitoneal administration of Doxil does not prevent intraabdominal recurrence of haemangiosarcoma in dogs; effective drug concentration is obtained after intraperitoneal administration and its clearance is comparable with IV administration	[24]
‘Stealth’ PEGylated liposomes	doxorubicin/Caelyx	cat	efficacy	response rate: 70%; 2 of 10 cats had complete responses and 5 of 10 cats had partial responses when Caelyx was administered together with daily radiotherapy	[22]
Non-PEGylated liposomes	doxorubicin/Myocet	dog	efficacy-case report	complete response with Myocet (35 mg/m2 IV every 3–6 weeks administered 6 times) in a dog with an immunoglobulin A-secreting chemotherapy-resistant myeloma	[25]
Non-PEGylated liposomes	doxorubicin/Myocet	dog	toxicity	no cardiomyopathy	[26]
Non-PEGylated liposomes	doxorubicin/Myocet	dog	preclinical toxicology	dose-limiting toxicity after intraperitoneal administration: chemical peritonitis; other adverse side effects: abdominal toxicity, myelosuppression and thoracic toxicity	[27]
Non-PEGylated liposomes	doxorubicin/Myocet	dog	preclinical toxicology	maximal tolerated dose: 2.25 mg/kg, adverse effect: pyrexia	[28]
Low temperature sensitive liposomes (LTSL)	doxorubicin	dog	toxicity and pharmacokinetic	dose-limiting toxicities: grade 4 neutropenia, acute death secondary to liver failure; adverse side effects: myelosuppression, cardiac failure; maximal tolerated dose: 0.93 mg/kg; response rate: 90% (6 of 20 dogs had partial response and 12 of 20 dogs had stable disease after at least 2 doses of LTSL-doxorubicin (0.7–1.0 mg/kg IV over 30 min) concurrently with local hyperthermia	[21]
‘Stealth’ PEGylated liposomes	cisplatin/SPI-77	dog	randomized, multi-centre efficacy	no differences in survival time in 40 dogs with spontaneous osteosarcoma that underwent limb amputation after adjuvant SPI-77 administration compared to carboplatin therapy	[29]
Liposomes	vincristine	dog	pharmacokinetic	increase therapeutic index of liposomal vincristine after single IV injection 0.07 mg/kg	[30]
Liposomes	paclitaxel	dog	pharmacokinetic and biodistribution	15-fold higher paclitaxel concentration in the lung at 2 h after paclitaxel liposomes IV administration than after free paclitaxel injection	[31]
Polysaccharide hyaluronan	cisplatin	dog	pharmacokinetic	1000-fold greater drug concentration in in tumours than in plasma after intratumoral injection (20 mg of cisplatin in the hyaluronan-cisplatin conjugate)	[53]
Polysaccharide hyaluronan	cisplatin	dog	efficacy and pharmacokinetics	3 of 7 dogs with oral and nasal squamous cell carcinoma had complete response and 3 of 7 dogs had stable disease (dose 10–30 mg/m2 intratumoral or into peritumoral submucosa once every 3 weeks, approximately 4 times); adverse side effects: myelosuppression, cardiotoxicity, hepatic toxicosis; lack of nephrotoxicity	[54]
PLGA-block(b)-PEG functionalized with a terminal triphenyl-phosphonium cation	platin (M) a	dog	safety and biodistribution	cross the blood brain barrier and accumulate in the brain; minimal adverse reactions after single IV injection at doses: 0.5 mg/kg, 2.9 mg/kg and 2.2 mg/kg	[57]
Lipid nanoemulsion	carmustine	dog	safety and efficacy pilot study	no difference between the treatment of LDE carmustine and free carmustine; adverse side effect: neutropenia	[33]
Nanocrystal	cisplatin	dog	biodistribution, proof of concept, safety	no results reported: study within recruitment or currently ongoing	[68] b
Nanocrystal	paclitaxel/Crititax	dog	safety and pharmacokinetics	maximal tolerated dose: 120 mg/m2, dose-limiting toxicity: 4 grade neutropenia; starting dose for phase I/II clinical trials: 80 mg/m2 IV	[58,68c]
Glutathione stabilized gold nanoparticles	doxorubicin	cat	in vitro and in ovo efficacy	higher cytotoxic effect of Dox conjugated to glutathione stabilized gold nanoparticles (Au-GSH-Dox) than free Dox in fibrosarcoma cell lines with high activity of P glycoprotein (FFS1WAW, FFS1 and FFS3), significantly reduced tumour size after single intratumoral injection of Au-GSH-Dox	[64,65]
PEG and BSA functionalized gold nanoparticles	Zn(DION2)Cl (TS262), CoCl2(H2O))(DION)2[(BF4)] (TS265)	dog	in vitro efficacy	higher cytotoxic effect of tested compounds in canine mammary tumour cell line (FR37-CMT) than free Dox or cisplatin	[66]

^a Prodrug of cisplatin; ^b Study No. AAHSD000024, AAHSD004339, AAHSD000176, AAHSD000370; ^c Study No. AAHSD000021.