In vitro/in vivo evaluation of agar nanospheres for pulmonary delivery of bupropion HCl

Figures & data

Table 1. Design of the experiment according to a D-optimal design for formulating agar nanosphres loaded with bupropion HCl.

Formulation	CaCl2 (%)	Homogenizer speed (rpm)	Agar (%)	HPβCD (%)	Particle size (nm)	Zeta potential (mV)	Loading efficiency (%)	RE300 (%)	PdI
C10S8000A2H1	10	8000	2	1	534.5 ± 18.6	−31.5	34.7 ± 0.3	90 ± 3	0.22
C6S10000A2H0.5	6	10 000	2	0.5	716.2 ± 163.7	−32.8	31.4 ± 1.1	63 ± 6	0.62
C10S8000A2H1	10	8000	2	1	525.9 ± 63.7	−30.2	41.5 ± 1.2	79 ± 4	0.54
C10S12000A1H0	10	12 000	1	0	613.4 ± 146.1	−27.2	29.4 ± 1.8	81 ± 10	0.56
C2S8000A2H0	2	8000	2	0	406.5 ± 79.6	−31.7	44.6 ± 2.7	70 ± 7	0.53
C6S10000A1.5H0	6	10 000	1.5	0	503.9 ± 181.3	−31.0	35.4 ± 2.2	86 ± 8	0.45
C2S10000A2H1	2	10 000	2	1	504.5 ± 114.8	−28.0	38.9 ± 0.9	80 ± 8	0.99
C6S8000A1.5H0.5	6	8000	1.5	0.5	807.2 ± 86.0	−25.9	39.5 ± 1.5	84 ± 5	0.51
C2S12000A1H1	2	12 000	1	1	491.3 ± 29.9	−22.9	18.9 ± 2.0	84 ± 26	0.38
C10S10000A1.5H0.5	10	10 000	1.5	0.5	492.3 ± 54.9	−25.4	34.9 ± 2.3	84 ± 17	0.9
C10S12000A1H0	10	12 000	1	0	310.3 ± 10.4	−21.7	27.7 ± 1.0	77 ± 7	0.33
C2S8000A1H1	2	8000	1	1	659.1 ± 80.2	−29.9	20.8 ± 0.7	86 ± 9	0.21
C6S8000A1H0	6	8000	1	0	670.1 ± 159.5	−27.9	18.9 ± 0.4	72 ± 8	0.73
C2S12000A2H0	2	12 000	2	0	519.7 ± 74.3	−34.2	43.6 ± 0.3	78 ± 4	0.48
C2S8000A2H0	2	8000	2	0	713.4 ± 97.3	−35.2	40.0 ± 1.0	78 ± 3	0.42
C10S12000A2H1	10	12 000	2	1	494.5 ± 19.3	−29.8	36.3 ± 0.3	91 ± 6	0.52
C10S8000A1 H0.5	10	8000	1	0.5	723.2 ± 304.7	−24.6	32.1 ± 0.5	87 ± 2	0.61
C6S10000A1.5H1	6	10 000	1.5	1	455.3 ± 153.3	−31.3	37.2 ± 0.6	86 ± 3	0.69
C10S10000A2H0	10	10 000	2	0	453.2 ± 19.0	−30.0	44.3 ± 0.9	78 ± 2	0.25
C10S8000A1.5H0	10	8000	1.5	0	619.9 ± 132.2	−28.0	45.6 ± 2.2	87 ± 10	0.63
C4S11000A1.25H0.5	4	11 000	1.25	0.5	443.4 ± 22.9	−34.7	31.7 ± 0.7	85 ± 4	0.72
C10S12000A2H1	10	12 000	2	1	674.1 ± 79.1	−31.7	30.0 ± 1.1	87 ± 5	0.47
C10S10000A1H1	10	10 000	1	1	357.3 ± 7.9	−29.0	26.6 ± 1.3	65 ± 4	0.58
C2S12000A2H0	2	12 000	2	0	641.7 ± 32.0	−27.3	44.1 ± 2.4	67 ± 5	0.51
C2S10000A1H0	2	10 000	1	0	776.6 ± 50.1	−37.1	36.6 ± 1.1	74±4	0.54

Table 2. Performance of developed neural network against prediction of nanocarrier features.

	Nanocarrier feature
Model performance	Particle size (nm)	PdI	Zeta potential (mV)	LE (%)	RE (%)
MSE	5314.19	0.0059	2.33	4.30	14.48
NMSE	0.37	0.20	0.18	0.08	0.30
MAE	43.23	0.0470	0.91	1.21	2.24

MSE, mean squared error; NMSE, normalized mean-squared error; MAE, mean of absolute error.

Figure 1. Scanning electron micrograph of agar nanospheres loaded with bupropion HCl.

Table 3. Predicted versus real values of the studied responses of the optimum formulation predicted by the GA methodology.

	Particle size (nm)	Zeta potential (mV)	Drug loading efficiency (%)	RE300 (%)	PdI
GA predict	466	−36.04	46.69	61.15	0.41
Actual	320 ± 90	−29.6	43.1 ± 0.28	66.7 ± 2	0.85
Error percent	31.33	17.87	7.69	9.08	107.32

Table 4. Pharmacokinetic parameters of bupropion HCl after i.v. and pulmonary administration of the simple solution and agar nanospheres of the drug (n = 6).

Pharmacokinetic parameter	Pulmonary simple solution	Pulmonary nanospheres	i.v. solution
Tmax (min)	60 ± 0	360 ± 0	–
Cmax (ng/ml)	9.93 ± 0.1	1927.93 ± 103.07	–
AUC0–t (µg/ml min)	11.792 ± 0.1	2286.16 ± 124.62	–
AUC0–∞ (µg/ml min)	28.804 ± 2.75	10 237.84 ± 2571.35	–
MRT (min)	2717.172 ± 319.65	5660.11 ± 1686.65	–
F (%)	0.253 ± 0.03	86.69 ± 2.43	–
t1/2α (min)	–	–	31.23 ± 11.4
t1/2β (min)	–	–	2027.44 ± 500.89
C0 (ng/ml)	–	–	4729.05 ± 519.59
CL (ml/min/kg)	–	–	3.55 ± 1.45
AUC0–t (µg/ml min)	–	–	4557.71 ± 296.4
AUC0–∞ (µg/ml min)	–	–	11 736.04 ± 2636.99
MRT (min)	–	–	2917.19 ± 727.01
Vss (ml/kg)	–	–	1239.24 ± 74.57

Figure 2. Plasma concentration–time profile of bupropion HCl after pulmonary administration of simple aqueous solution, pulmonary administration of the drug loaded in agar nanospheres, and i.v. administration of simple aqueous solution. In each case the dose of drug was 5 mg/kg.