Improved biological properties and hypouricemic effects of uricase from Candida utilis loaded in novel alkaline enzymosomes

Figures & data

Figure 1 Schematic diagram of uricase-containing lipid vesicles (UOXLVs) catalyzing the transformation of uric acid into allantoin.

Figure 2 Lineweaver–Burk profiles of the uricase-containing lipid vesicles (UOXLVs) and free uricase (n = 3).

Figure 3 Time courses of the remaining activity of the uricase-containing lipid vesicles (UOXLVs) and free uricase in the presence of plasma (closed squares and triangles, respectively).

Table 1 Pharmacokinetic parameters of uricase-containing lipid vesicles (UOXLVs) and free uricase in rats using a model-independent approach

Parameter	UOXLVs**	Free uricase
AUC0−t (mU h/mL)	221.63 ± 21.5	10.10 ± 0.75
AUC0–∞ (mU h/mL)	227.60 ± 25.3	10.10 ± 0.75
MRT0–t (h)	3.45 ± 0.17	0.55 ± 0.04
MRT0–∞ (h)	3.93 ± 1.06	0.55 ± 0.04
Cmax (mU/mL)	45.40 ± 3.44	26.10 ± 2.7
Tmax (h)	0.50 ± 0	0.017 ± 0
t1/2 (h)	2.79 ± 0.29	0.38 ± 0.03
V (mL/kg)	44.04 ± 2.79	76.64 ± 1.50
CL (mL/h/kg)	9.02 ± 0.87	198.02 ± 14.01

Notes: Data represent mean value ± standard deviation, n = 6;

** P < 0.01, compared with free uricase.

Abbreviations: AUC, area under the plasma concentration–time curve; MRT, mean residence time; C_max, maximum concentration; T_max, peak time; t_1/2, half-life; V, apparent volume of distribution; CL, clearance.

Figure 4 Plasma uricase activity versus time profiles after intravenous administration of uricase-containing lipid vesicles (UOXLVs) (closed squares) and free uricase (open squares) in rats.

Note: Each point represents the mean ± standard deviation (n = 6).

Figure 5 The plasma uric acid concentration versus time profiles after intravenous injection of the solvent (normal group, closed squares), hypoxanthine and oxonic acid (hyperuricemia model group, open squares), free uricase (closed triangles), and uricase-containing lipid vesicles (UOXLVs) (open triangles) in rats. The plasma uric acid concentration was determined by uric acid assay kit.

Note: Data are expressed as mean ± standard deviation (n = 6).

Figure 6 Immunogenicity test results. (A) Antisera dilution ratio; (B) antibody titer.

Note: The data represent the mean ± standard deviation (n = 6).

Abbreviation: UOXLVs, uricase-containing lipid vesicles.