Poly(n-butylcyanoacrylate) nanoparticles for oral delivery of quercetin: preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats

Figures & data

Figure 1 Schematic illustration of encapsulation of QT-PBCA NPs by emulsion polymerization.

Abbreviations: QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80.

Figure 2 Morphology of encapsulated QT-PBCA NPs and QT-PBCA+P-80.

Notes: Typical particle size distribution graph shows sharp, narrow area peaks indicating the homogeneity of QT-PBCA NPs at 161.1±0.44 nm (A) and QT-PBCA+P-80 at 166.6±0.33 nm (B); Transmission electron microscopy images of QT-PBCA NPs (C) and QT-PBCA+P-80 (D) at 30,000×.

Abbreviations: QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80.

Figure 3 (A) Absorption spectrum of free QT and QT-PBCA NPs; (B) Visual observation of prepared QT-PBCA NPs suspended in water (a) and free QT solution suspended in water (b).

Abbreviations: QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles.

Figure 4 FTIR spectrum of n-BCA monomer (A), blank PBCA NPs (B), QT-PBCA NPs (C), and free QT (D).

Notes: A,B and C arrow indicates a C=N peak at 2,249.83 cm⁻¹ on n-BCA is also present in the spectra of blank PBCA NPs and QT-PBCA NPs, indicating that C=N did not take part in the polymerization reaction; D arrow indicates a major characteristic broader bands corresponding to the OH phenolic stretch at 3,385.07 cm⁻¹.

Abbreviations: FTIR, Fourier transform infrared spectroscopy; n-BCA, n-butylcyanoacrylate; PBCA, poly(n-butylcyanoacrylate); NPs, nanoparticles; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; QT, quercetin.

Figure 5 DSC curves of free QT (A), QT-PBCA NPs (B), and blank PBCA NPs (C).

Abbreviations: DSC, differential scanning calorimetry; QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; PBCA, poly(n-butylcyanoacrylate); NPs, nanoparticles.

Figure 6 X-ray powder diffraction of free QT (A), QT-PBCA NPs (B), and blank PBCA NPs (C).

Abbreviations: QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; PBCA, poly(n-butylcyanoacrylate); NPs, nanoparticles.

Figure 7 Stability study of free QT, QT-PBCA NPs, and QT-PBCA+P-80 in SGF (A) and SIF (B).

Note: Data are represented as mean ± SD (n=3).

Abbreviations: QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80; SGF, simulated gastric fluid; SIF, simulated intestinal fluid; SD, standard deviation; h, hours.

Figure 8 Cumulative release profiles of QT from QT-PBCA NPs and QT-PBCA+P-80 in comparison with the free drug.

Note: Results are presented as mean ± SD (n=3).

Abbreviations: QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80; SD, standard deviation; h, hours.

Table 1 Stability study of QT-PBCA NPs

Days	Physical appearance	Particle size (nm)	Polydispersity index (PDI)	Zeta potential (mV)	Drug entrapment efficiency (%)
0	Yellowish white	161.19±0.44	0.289±0.017	−27.28±0.60	79.86±0.45
30	Yellowish white	161.88±0.18	0.287±0.041	−27.23±0.89	79.44±0.71
60	Yellowish white	164.53±0.73	0.298±0.023	−27.04±0.36	78.91±0.56
120	Yellowish white	166.9±0.45	0.307±0.031	−26.59±0.78	78.02±0.33
180	Yellowish white	169.32±0.31	0.312±0.025	−26.88±0.49	78.75±0.68

Note: Data are mean ± SD (n=3).

Abbreviations: QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; SD, standard deviation.

Table 2 Plasma pharmacokinetics parameters of free QT solution, QT-PBCA NPs, and QT-PBCA+P-80, after single oral administration of 50 mg/kg body weight in rats

Pharmacokinetics parameter	Free QT	QT-PBCA NPs	QT-PBCA+P-80
Cmax (μg/mL)	11.26±0.09	15.30±0.12*,#	19.11±0.25*
Tmax (hours)	6	8*	8*
t1/2 (hours)	6.09±1.71	14.31±5.91*#	18.84±5.14*
AUCtotal (μg·h/mL)	104.22±2.05	248±6.82*,#	313.97±7.88*

Notes: Data represented as mean ± SD (n=5);

* significantly different of free QT (P<0.05);

# significantly different of QT-PBCA NPs from QT-PBCA+P-80 (P<0.05).

Abbreviations: C_max, maximum plasma concentration; t_1/2, half-life; AUC, area under the concentration time curve; QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80; SD, standard deviation; T_max, time to reach C_max.

Figure 9 In vivo mean plasma drug concentration–time profiles of quercetin in rats after oral administration in Wistar rats of free QT, QT-PBCA NPs, and QT-PBCA+P-80.

Note: All values reported are mean ± SD (n=5).

Abbreviations: QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80; SD, standard deviation; h, hours.

Table 3 Pharmacokinetics parameters of tissue distribution of QT after oral administration of QT solution, QT-PBCA NPs, and QT-PBCA+P-80 to rats with dose of 50 mg/kg

Tissue	Cmax (µg/mL)	AUCtotal (µg·h/mL)
Free QT
Brain	22.91±3.35	201.76±43.63
Heart	18.88±2.09	124.29±60.40
Liver	21.44±3.97	248.91±11.36
Kidney	43.67±2.28	603.66±35.23
Spleen	19.44±1.35	284.09±27.66
QT-PBCA nanoparticles
Brain	33.28±1.27*,#	298.66±25.44*,#
Heart	17.45±3.71*,#	92.85±1.81*,#
Liver	25.88±3.01*	214.74±23.21*
Kidney	31.65±2.81*	397.75±17.98*
Spleen	26.21±1.17*	208.27±44.51*
QT-PBCA+P-80
Brain	37.43±1.53*	386.47±71.41*
Heart	15.76±0.43*	104.79±9.21*
Liver	27.11±1.91*	236.08±54.35
Kidney	30.04±2.31*	362.40±29.16*
Spleen	25.83±2.67*	190.70±60.28

Notes: Data represented as mean ± SD (n=5);

* significantly different of free QT (P<0.05);

# significantly different of QT-PBCA NPs from QT-PBCA+P-80 (P<0.05).

Abbreviations: C_max, maximum plasma concentration; AUC, area under the concentration time curve; QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80; SD, standard deviation.

Figure 10 In vivo biodistribution studies on Wistar rats.

Notes: Tissue concentration–time profiles of QT after oral administration of free QT solution (A), QT-PBCA NPs (B), and QT-PBCA+P-80 (C). Data represented as mean ± SD (n=5).

Abbreviations: QT, quercetin; QT-PBCA NPs, quercetin-loaded poly(n-butylcyanoacrylate) nanoparticles; P-80, polysorbate-80; SD, standard deviation; h, hours.