DPPC-coated lipid nanoparticles as an inhalable carrier for accumulation of resveratrol in the pulmonary vasculature, a new strategy for pulmonary arterial hypertension treatment

Figures & data

Figure 1. Characterization of Res-DPPC-LNs. (A) the appearance of Res-DPPC-LNs suspensions, (B) transmission electron microscopic image, (C) size distribution, (D) zeta potential, (E) In vitro release profiles of plain Res and Res-DPPC-LNs suspensions in pH 7.4 PBS at 37 °C (Data represent mean ± SD, n = 6). () plain Res, () Res-DPPC-LNs.

Table 1. Results of model fitting of release curves of Res-DPPC-LNs in PBS.

Model	Equation	R^2	n
Zero-order	F=k0t	0.7992	/
First-order	F = 100[1-$\mathrm{ }{e}^{-k1\mathrm{t}}$]	0.9726	/
Higuchi	F=kH$t^{0.5}$	0.9167	/
Makoid-Banakar	F=kMB$t^n{e}^{-\mathrm{\text{kt}}}$	0.9927	0.708

Figure 2. Physicochemical stability of Res-DPPC-LNs: (A) entrapment efficiency, (B) PDI, (C) size and (D) zeta potential. Data represent mean ± SD, n = 3.

Figure 3. (A) Viability of rat PASMCs upon incubation with formulations or individual components of formulation. (mean ± SD, n = 6), (B) Representative fluorescence microscopic images showing the uptake of Free Rh123 and Rh123-DPPC-LNs by pulmonary arterial smooth muscle cells. Blue color represents cell nucleus stained with DAPI. Red color represents Rh123, (C) Effect of Plain Res and Res-DPPC-LNs on 5-HT induced PASMC proliferation (mean ± SD, n = 6). *** P < 0.001.

Figure 4. (A) In vivo absorption profile of Res following intratracheal inhalation of the Res-DPPC-LNs and intravenous administration of the Res solution to rats. (dose = 10 mg/kg, mean ± SD, n = 6), (B) The Res lung concentration-time profiles following intratracheal inhalation of the Res-DPPC-LNs and intravenous administration of the Res solution to rats. (dose = 10 mg/kg, mean ± SD, n = 6).

Table 2. The plasma pharmacokinetic parameters of Res following intratracheal inhalation of the Res-DPPC-LNs and intravenous administration of the Res solution to rats.

Parameters	Intratracheal administration Res-DPPC-LNs	Intravenous administration plain Res	p Value
MRT(h)	5.01 ± 0.91	0.41 ± 0.02	0.00
tmax(h)	0.50 ± 0.00	–	–
t1/2(h)	7.73 ± 2.29	0.32 ± 0.02	0.00
AUC0→t(μg/mL·h)	5.08 ± 0.44	3.35 ± 0.43	0.00
AUC0→∞(μg/mL·h)	6.44 ± 0.77	3.39 ± 0.44	0.00
AUMC0→∞(μg/mL·h^2)	33.26 ± 10.17	1.40 ± 0.25	0.00
Cl/F (L/h)	1.57 ± 0.18	3.00 ± 0.39	0.00
Vss/F (mL)	17.17 ± 4.00	1.32 ± 0.09	0.00
Cmax (mg/mL)	3.28 ± 0.22	–	–

(dose = 10 mg/kg, mean ± SD, n = 6).