Implications of formulation design on lipid-based nanostructured carrier system for drug delivery to brain

Figures & data

Figure 1. Particle size distribution of optimized IDE lipid-based nanostructured carriers.

Table 1. Average particle size measured by LD during 3 months of storage at room temperature.

IDE NLCs	Day 1	Day 60	Day 90	Mean	RSD
LD10 (nm)	76.5	84.3	90.2	83.66	6.14
LD50 (nm)	117.3	119.2	130.0	122.16	6.85
LD90 (nm)	174.1	180.4	191.2	181.90	8.64

Figure 2. X-ray diffraction patterns: (A) IDE (B) Precirol ATO 5 (C) IDE lipid-based nanostructured carriers.

Figure 3. DSC Thermograms: (A) IDE (B) Precirol ATO 5 (C) IDE lipid-based nanostructured carriers.

Figure 4. Transmission electron microphotographs of IDE lipid-based nanostructured carriers.

Figure 5. In vitro release profile of IDE from lipid-based nanostructured carriers and aqueous dispersions.

Table 2. In vitro release profile of IDE from lipid-based nanostructured carriers and aqueous dispersions.

	% Drug release
Time (h)	IDE lipid-based nanostructured carriers	IDE aqueous dispersions
0.16	4.06 ± 0.34	3.76 ± 0.47
0.33	8.33 ± 0.41	6.73 ± 0.54
0.5	12.34 ± 0.53	9.97 ± 0.70
1	16.02 ± 0.72	14.58 ± 0.51
2	21.20 ± 0.49	23.62 ± 0.72
3	27.05 ± 0.57	50.41 ± 0.67
4	36.20 ± 0.45	64.97 ± 0.81
5	45.98 ± 0.61	79.80 ± 0.39
6	51.96 ± 0.24	91.04 ± 0.57
9	62.02 ± 0.43
12	74.95 ± 0.78
18	85.76 ± 0.56
24	93.56 ± 0.39

Table 3. Relative pharmacokinetic parameters of formulations containing IDE measured in blood plasma and brain compartment.

Compartments	Formulation	Cmax (µg/ml)	tmax (h)	AUC0 → 24 h (µg h/ml)	Relative BA (%)
Plasma	IDE NLCs	43.452 ± 4.479	9.33 ± 0.35	6 229 441.495 ± 264 546.334	4.6
	IDE aqueous dispersions	7.823 ± 1.340	5.08 ± 0.18	1 349 762.084 ± 37 225.487	–
Brain	IDE NLCs	9.910 ± 0.567	8.89 ± 0.24	1 410 879.021 ± 12 231.132	2.8
	IDE aqueous dispersions	1.891 ± 0.243	4.90 ± 0.14	503 885.014 ± 3453.243	–

Table 4. Stability study of IDE lipid-based nanostructured carriers stored at 5 ± 3 °C and 40 ± 2 °C temperatures.

Days	0	30	60	90
Particle size (nm)	5 ± 3 °C	172.0 ± 2.1	172.8 ± 2.4	173.1 ± 2.3	175.1 ± 2.2
	40 ± 2 °C	174.1 ± 2.6	174.3 ± 2.3	175.2 ± 2.4	176.0 ± 3.5
Zeta potential (mV)	5 ± 3 °C	−20.10 ± 2.45	−19.10 ± 2.88	−18.23 ± 2.93	−17.24 ± 2.40
	40 ± 2 °C	−18.65 ± 1.13	−18.43 ± 3.40	−17.36 ± 3.18	−15.98 ± 2.69
Entrapment efficiency (% EE)	5 ± 3 °C	91.70 ± 2.10	91.07 ± 1.75	90.28 ± 2.29	89.03 ± 2.15
	40 ± 2 °C	90.68 ± 2.90	89.50 ± 1.62	88.74 ± 2.35	87.03 ± 2.29
In vitro drug release (%)	5 ± 3 °C	92.08 ± 1.25	92.23 ± 1.34	93.01 ± 2.03	93.03 ± 1.99
	40 ± 2 °C	93.56 ± 0.39	94.01 ± 0.78	94.78 ± 1.19	94.36 ± 2.17