Squarticles as the nanoantidotes to sequester the overdosed antidepressant for detoxification

Figures & data

Table 1 The characterization of nanosystems by particulate size, PDI, and zeta potential

Formulation	Size (nm)	PDI	Zeta potential (mV)
Anionic squarticles	97.19±0.19	0.30±0.02	−35.55±1.65
Cationic squarticles	122.23±0.55	0.21±0.01	−27.60±0.44
SLNs	190.63±0.19	0.20±0.01	−32.33±0.12
Liposomes	139.07±2.60	0.14±0.02	−42.17±0.15
Niosomes	92.59±0.41	0.24±0.01	−5.32±0.91

Note: Each value represents the mean ± SD (n=3).

Abbreviations: PDI, polydispersity index; SLNs, solid lipid nanoparticles.

Figure 1 Amitriptyline entrapment, morphology, and polarity of the nanosystems.

Notes: (A) Amitriptyline entrapment percentage into the nanosystems as a function of time; (B) the morphology of anionic and cationic squarticles viewed by TEM; and (C) the polarity of anionic and cationic squarticles determined by the solvatochromism of Nile red. Each value represents the mean and SD (n=4).

Abbreviations: ILEs, intravenous lipid emulsions; SLNs, solid lipid nanoparticles; TEM, transmission electron microscopy.

Figure 2 Interaction of amitriptyline with nanoparticulate surface and release from the nanosystems.

Notes: (A) Isothermal titration calorimetry data from the titration of amitriptyline into squarticles and ILEs; (B) the encapsulation efficiency of amitriptyline in squarticles; and (C) the release of amitriptyline from squarticles. Each value represents the mean and SD (n=4).

Abbreviations: ILEs, intravenous lipid emulsions; K_a, association constant.

Figure 3 In vivo and ex vivo bioimaging of rats receiving free dye and dye-loaded squarticles.

Note: (A) Real-time imaging for viewing the residence in circulation and (B) ex vivo bioimaging of the organs of the representative animals at the end of the experiment.

Abbreviations: DiR, 1,1′-dioctadecyl-3,3,3′,3′-tetramethyl-indotricarbocyanine iodide; GI tract, gastrointestinal tract.

Table 2 The percentage of near-infrared signal in different organs of rats by intravenous injection of free iFluor 790 and the squarticles containing iFluor 790

Organ	Free iFluor 790	Anionic squarticles	Cationic squarticles
Brain	6.71±1.50	3.76±0.41	4.11±0.36
Heart	22.89±1.82	11.06±2.69	9.79±1.26
Lungs	22.27±5.04	15.25±2.47	27.35±3.26
Kidneys	10.61±0.95	21.03±3.99	21.13±1.70
Liver	23.31±0.89	33.18±3.63	21.82±2.68
Spleen	3.54±0.58	9.97±2.17	9.17±0.24
GI tract	7.66±0.72	5.74±0.51	6.64±0.10

Note: Each value represents the mean ± SD (n=6).

Abbreviation: GI tract, gastrointestinal tract.

Figure 4 Pharmacokinetic and pharmacodynamic evaluations of the effect of squarticles and ILEs on amitriptyline intoxication.

Notes: (A) The experimental protocol; (B) concentration of amitriptyline in the plasma after intravenous administration of squarticles and ILEs; (C) biodistribution of amitriptyline in the peripheral organs after intravenous administration of squarticles and ILEs; (D) the organ/plasma ratio of amitriptyline concentration after intravenous administration of squarticles and ILEs; and (E) the mean arterial pressure of amitriptyline-intoxicated rats after intravenous administration of squarticles and ILEs. Each value represents the mean and SD (n=10 for pharmacokinetic study and n=6 for pharmacodynamic study).

Abbreviations: ILEs, intravenous lipid emulsions; inj, injection.

Figure 5 Effect of intravenous administration of squarticles and ILEs on the survival rate of rats receiving overdose of amitriptyline.

Notes: (A) The experimental protocol and (B) Kaplan–Meier survival curve of the rats. Each value represents the mean and SD (n=12).

Abbreviation: ILEs, intravenous lipid emulsions.