Pharmacokinetics of quercetin-loaded nanodroplets with ultrasound activation and their use for bioimaging

Figures & data

Table 1 Characterization of nanodroplets without drug loading and the nanodroplet-encapsulated quercetin formulation by particle size, zeta potential, polydispersity index, and drug encapsulation

	Size (nm)	Zeta potential (mV)	PDI	Encapsulation (%)
Nanodroplets (no drug)	270.1±24.01	−42.18±7.64	0.21±0.01
NQ	278.6±10.18	−34.66±2.18	0.34±0.01	99.41±0.20

Note: The data are expressed as the mean ± standard deviation (n=3).

Abbreviations: NQ, nanodroplet-encapsulated quercetin; PDI, polydispersity index.

Figure 1 Percentage weight remaining in the NQ formulation as a function of time in the stability experiment in a 37°C oven and 4°C freezer. Each value represents the mean ± standard deviation (n=4).

Abbreviation: NQ, nanodroplet-encapsulated quercetin.

Figure 2 Transmission electron microscopic micrograph of the nanodroplet-encapsulated quercetin formulation. Original magnification 60,000×.

Figure 3 In vitro release profiles for quercetin over time across a cellulose membrane for a control solution of PEG 400 +20% ethanol and perfluorocarbon nanodroplets. A 0.5 mL plasma aliquot was added to the donor compartment of a Franz diffusion cell. Each value represents the mean ± standard deviation (n=3). *P<0.05 versus the quercetin group.

Abbreviations: NQ, nanodroplet-encapsulated quercetin; PEG, polyethylene glycol.

Figure 4 Effect of ultrasound at 1 MHz with an intensity of 2.0 W/cm² and a duty cycle of 20% on in vitro release of quercetin from perfluorocarbon nanodroplets across a cellulose membrane. A 0.5 mL plasma aliquot was added to the donor compartment of the Franz diffusion cell. Each value represents the mean ± standard deviation (n=3). *P<0.05 versus the value for the NQ sample.

Abbreviation: NQ, nanodroplet-encapsulated quercetin.

Figure 5 Ultrasonograph of the bladder in the normal rats.

Notes: (A) Preinjection, (B) injection of double-distilled H₂O, and (C) injection of nanodroplets. Red-circled areas indicate monitoring region.

Figure 6 Ultrasonograph of nanodroplets inside the abdominal vein in a rat model.

Notes: (A) Before and (B) after intravenous administration of nanodroplets at 30 seconds. (C) nanobubbles triggered by ultrasonic treatment and (D) after triggering of nanobubbles. Red-circled areas indicate monitoring region.

Table 2 Pharmacokinetic parameters of quercetin 3 mg/kg and the equivalent quercetin dose for the nanodroplet-encapsulated quercetin formulation in rat plasma after administration of an intravenous bolus

Pharmacokinetic parameters	Quercetin	Quercetin + U (3 min)	NQ	NQ + U (3 min)
C5 min (μg/mL)	0.5±0.1	0.9±0.2	2.3±0.3*	2.8±0.3*
AUC (μg/mL per minute)	18.4±7.0	37.0±10.5	60.5±5.9*	67.6±6.8*
Elimination half-life (minutes)	32±19	29±18	135±43*	72±10*
Clearance (mL/minute per kg)	281±81	183±96	51.6±4.2*	46.1±3.5*

Notes: The data are expressed as the mean ± standard error of the mean (n=6).

* P<0.05 versus the quercetin group. C_{5 min} is 5-minute serum concentration after quercetin administration; Quercetin + U (3 min) is ultrasound treatment after 3 minutes quercetin administration; NQ + U (3 min) is ultrasound treatment after 3 minutes NQ administration.

Abbreviations: AUC, area under the concentration–time curve; U, treatment with ultrasound; NQ, nanodroplet-encapsulated quercetin.

Figure 7 Concentration curve of quercetin in rat plasma after intravenous administration of quercetin 3 mg/kg, quercetin triggered with ultrasound at 3 minutes (quercetin + U, 3 mg/kg), NQ 3 mg/kg, and NQ triggered with ultrasound (NQ + U, 3 mg/kg) at 3 minutes, respectively (mean ± standard error of the mean; n=6).

Abbreviations: iv, intravenously; U, treatment with ultrasound; NQ, nanodroplet-encapsulated quercetin.