Table 2. Orthogonal experimental drug design (OEDD).

	A	B	C	D	PS	ZP	PDI	% EE (OA)	% EE (DOX)	% EE (Comb.)	Range (PS-EE)	Batch ID
Cumulative impact of the study factors on physicochemical attributes at the stated level	1	1	1	1	119.73 ± 7.27	−18.26 ± 5.22	0.17 ± 0.08	59.73 ± 4.21	46.77 ± 3.15	53.25 ± 3.68	66.49	A1B1C1D1-F1
	2	1	2	2	86.27 ± 22.02	−23.49 ± 8.72	0.19 ± 0.02	70.61 ± 3.56	62.60 ± 3	66.60 ± 3.28	19.66	A1B2C2D2-F2
	3	1	3	3	103.93 ± 7.15	−18.52 ± 10.38	0.24 ± 0.03	69.41 ± 2.84	89.78 ± 1.03	79.60 ± 1.93	24.34	A1B3C3D3-F3
	4	2	1	3	88.17 ± 10.19	−16.37 ± 3.23	0.26 ± 0.04	79.63 ± 4.61	79.35 ± 3.46	79.49 ± 4.04	8.68	A2B1C2D3-F4
	5	2	2	1	121.52 ± 13.93	−25.40 ± 3.01	0.28 ± 0.01	78.50 ± 8.63	85.42 ± 3.95	81.96 ± 6.29	39.56	A2B2C3D1-F5
	6	2	3	2	117.27 ± 6.88	−19.02 ± 5.89	0.33 ± 0.03	91.84 ± 1.66	85.37 ± 18.24	88.60 ± 9.95	28.66	A2B3C1D2-F6
	7	3	1	2	147.53 ± 10.72	−20.44 ± 12.76	0.32 ± 0.02	81.53 ± 3.68	71.13 ± 6.57	76.33 ± 5.12	71.20	A3B1C3D2-F7
	8	3	2	3	194.70 ± 10.29	−17.09 ± 3.5	0.34 ± 0.04	77.67 ± 3.59	50.24 ± 8.64	63.95 ± 6.12	130.75	A3B2C1D3-F8
	9	3	3	1	176.37 5.82	−13.86 ± 1.91	0.31 ± 0.03	65.30 ± 4.93	94.77 ± 11.15	80.03 ± 8.04	96.33	A3B3C2D1-F9
K1	199.45	209.07	205.8	215.24	K1 is the sum of %EE (Comb.) at level 1
K2	250.05	212.51	226.12	231.53	K2 is the sum of %EE (Comb.) at level 2
K3	220.31	248.23	237.89	223.04	K3 is the sum of %EE (Comb.) at level 3
k1	66.48	69.69	68.6	71.75	k1 is the average of K1
k2	83.35	70.84	75.37	77.18	k2 is the average of K2
k3	73.43	82.74	79.3	74.35	k3 is the average of K3
R	16.87	13.05	10.7	5.43	R is the range difference at three levels (k1,k2,k3)
	A2	B3	C3	D2	A possible best drug design A2B3C3D2