Influence of PEG coating on the oral bioavailability of gold nanoparticles in rats

Figures & data

Figure 1. Characterization of AuNPs. Panel A. Transmission electron micrograph of uncoated 5 nm particles. The average primary size was 5 ± 2 nm (mean ± SD) based upon measurement of 100 particles. Panel B. Particle size distribution of 5 nm AuNPs. Particle size distributions for 1 kDa, 2 kDa and 5 kDa PEG-coated particles. The average hydrodynamic radiuses were 12 ± 2, 16 ± 2 and 22 ± 4, respectively (mean ± SD).

Figure 2. Blood concentration versus time profile following intravenous administration of 1, 2 or 5 kDa PEG-coated 5 nm AuNPs. Rats were administered a single intravenous dose (0.8 mg/kg) of 1, 2 or 5 kDa PEG coated 5 nm AuNPs. Blood samples were taken over time for up to 24 h and AuNP concentrations in blood were measured. Results are plotted beginning with the first sample after the dose (0.1 h) and are expressed as mean ± SD (N = 3).

Table 1. Pharmacokinetic parameters following intravenous and oral administration of 1, 2 and 5 kDa PEG-coated gold nanoparticles.

	PEG-coated gold nanoparticle
Parameter	1 kDa	2 kDa	5 kDa
Intravenous administration (0.8 mg/kg)
T½ (h)	17.4 ± 2.8	13.2 ± 7.2	7.3 ± 2.0
CL (mL/h)	0.55 ± 0.09	0.54 ± 0.32	1.91 ± 2.44
Vd (mL)	12.6 ± 0.7	8.2 ± 0.9	22.8 ± 31.6
AUC0 to infinity (h*ng/L)	296,700 ± 49,200	364,800 ± 174,500	227,700 ± 175,900
Oral administration (8 mg/kg)
AUC0 to infinity (h*ng/L)	3,000 ± 1,510^A	858 ± 170^B	263 ± 126^B
F	0.0010	0.00023	0.00035

Results are expressed as mean ± SD; N = 3 for intravenous doses and N = 5 for oral doses.

T ½: half-life; CL: clearance; Vd: volume of distribution; AUC: area under the blood concentration versus time curve; F: bioavailability.

Blood concentration data were analyzed using Phenix software using a non-compartmental approach. Different letter superscripts indicate significant differences among groups, p < 0.05.

Figure 3. Blood concentration versus time profile following oral administration of uncoated or 1, 2 or 5 kDa PEG-coated 5 nm AuNPs. Rats were administered a single oral dose (8.0 mg/kg) of 1, 2 or 5 kDa PEG coated 5 nm AuNPs by gavage. Blood samples were taken over time for up to 48 hours and AuNP concentrations in blood were measured. Results are plotted beginning with 0 h (just prior to the dose) and are expressed as mean ± SD (N = 5).

Figure 4. Tissue distribution of 1, 2 and 5 kDa PEG-coated 5 nm AuNPs following intravenous administration. Gold content was measured in liver, spleen, and kidney at sacrifice 24 h after an intravenous dose (0.8 mg/kg) of either 1, 2 or 5 kDa PEG-coated 5 nm AuNPs. A) Gold concentration in tissues. B) Mass of gold in the tissue based upon tissue concentration and total weight of the organ. Results are presented as mean ± SD, N = 5. Bars with letter superscripts (A or B) denote significant differences among PEG-coated particle types; bars with different letter superscripts are significantly different p < 0.05.

Figure 5. Tissue distribution of 1, 2 and 5 kDa PEG-coated 5 nm AuNPs following oral administration. Gold content was measured in liver, spleen, and kidney at sacrifice 48 h after an oral dose (8.0 mg/kg) of either 1, 2 or 5 kDa PEG-coated 5 nm AuNPs. A) Gold concentration in tissues. B) Mass of gold in the tissue based upon tissue concentration and total weight of the organ. Results are presented as mean ± SD, N = 5. Bars with letter superscripts (A, B or AB) denote significant differences among PEG-coated particle types; bars with different letter superscripts are significantly different p < 0.05.