Pharmacokinetics of oral and subcutaneous administration of free and liposomal levamisole in goats.

BACKGROUND

New drug formulations are needed to prevent antiparasitic resistance in goats. Liposomes are one of the most commonly used drug delivery systems for this purpose.

OBJECTIVES

This study aims to determine the pharmacokinetics of free and liposomal levamisole in goats after single oral (O) and subcutaneous (SC) administrations at a dose of 7.5 mg/kg. It was hypothesized that liposomal levamisole in goats may improve its pharmacokinetic profile by increasing systemic exposure and improving drug bioavailability compared to free levamisole.

METHODS

The study developed a levamisole liposome and investigated relevant parameters: particle size, zeta potential, polydispersity index, encapsulation efficiency, pH, and morphology. Blood samples were collected using heparinized tubes from the jugular vein through a cannula at 0 (control), 0.083, 0.167, 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h. Free and liposomal levamisole plasma concentrations were measured using high-performance liquid chromatography ultraviolet (HPLC-UV).

RESULTS

The developed levamisole liposomes were characterized by an average PS of 204.3 ± 3.7 nm, a PDI of 0.251 ± 0.033, a ZP of -16.3 ± 0.5 mV, and an EE of 76.08 ± 0.03%. Liposomal formulations showed significantly higher values than free formulations in terms of λz (O: 91.3%↑, FLO: 0.046 ± 0.006 h-1, LLO: 0.088 ± 0.01 h-1; SC: 9.2%↓, FLSC: 0.076 ± 0.021 h-1, LLSC: 0.069 ± 0.018 h-1), Cmax (O: 70.5%↑, FLO: 1211.219 ± 410.407 ng/mL, LLO: 2064.533 ± 412.011 ng/mL; SC: 14.1%↑, FLSC: 2050.623 ± 186.165 ng/mL, LLSC: 2340.168 ± 348.122 ng/mL), Clast (O: 56.0%↑, FLO: 77.538 ± 9.053 ng/mL, LLO: 120.969 ± 57.718 ng/mL; SC: 85.4%↑, FLSC: 112.795 ± 30.262 ng/mL, LLSC: 209.142 ± 45.257 ng/mL), AUC0-t (O: 148%↑, FLO: 4134.794 ± 745.011 h*ng/mL, LLO: 10261.449 ± 3915.247 h*ng/mL; SC: 47%↑, FLSC: 9922.304 ± 3223.356 h*ng/mL, LLSC: 14575.461 ± 3677.068 h*ng/mL), and AUC0-∞ (O: 98%↑, FLO: 5876.493 ± 1047.383 h*ng/mL, LLO: 11653.385 ± 4530.480 h*ng/mL; SC: 54%↑, FLSC: 11498.826 ± 3513.92 h*ng/mL, LLSC: 17728.218 ± 3361.133 h*ng/mL) parameters. In terms of route of administration, subcutaneous administration significantly increased Cmax, Clast, AUC0-t, and AUC0-∞ values. In oral administration, the t1/2 (48.6%↓, FLO: 15.463 ± 2.242 h, LLO: 7.956 ± 0.880 h) and ClT (45.3%↓, FLO: 1.310 ± 0.232 L/h/kg, LLO: 0.717 ± 0.235 L/h/kg) values of the drug were higher in the free formulation. The interaction between formulation and route of administration was significant for the λz, t1/2, and Vd/F parameters. Subcutaneous administration yielded enhanced pharmacokinetic performance than oral administration for the liposomal formulation, specifically in Clast (73%↑, LLO: 120.969 ± 57.718 ng/mL, LLSC: 209.142 ± 45.257 ng/mL), AUC0-t (42%↑, LLO: 10261.449 ± 3915.247 h*ng/mL, LLSC: 14575.461 ± 3677.068 h*ng/mL), AUC0-∞ (52%↑, LLO: 11653.385 ± 4530.480 h*ng/mL, LLSC: 17728.218 ± 3361.133 h*ng/mL), Cmax (13%↑, LLO: 2064.533 ± 412.011 ng/mL, LLSC: 2340.168 ± 348.122 ng/mL), and ClT (66.5%↓, LLO: 0.717 ± 0.235 L/h/kg, LLSC: 0.439 ± 0.101 L/h/kg).

CONCLUSIONS

As a result, it was concluded that liposomal levamisole may exhibit potentially improved efficacy than free levamisole in goats. Future study directions include investigating liposomal levamisole in different species to determine whether improved efficacy is consistent.