Formulation and delivery of itraconazole to the brain using a nanolipid carrier system

Figures & data

Table 1 Compositions for the preparation of itraconazole-loaded nanostructured lipid carriers

Formulation	Drug (% w/w)	Lipid (% w/w)		Surfactant (% w/w)		Water (% w/w)
		PREa	TRAa	TW80b	HS15c
F1	0.06	1	1	2	–	95.94
F2	0.06	1	1	–	2	95.94
F3	0.06	1	1	1	1	95.94
F4	0.06	1	1	4	–	93.94
F5	0.06	1	1	–	4	93.94
F6	0.06	1	1	2	2	93.94
F7	0.06	1.5	0.5	2	–	95.94
F8	0.06	1.5	0.5	–	2	95.94
F9	0.06	1.5	0.5	1	1	95.94
F10	0.06	1.5	0.5	4	–	93.94
F11	0.06	1.5	0.5	–	4	93.94
F12	0.06	1.5	0.5	2	2	93.94

Notes:

a Gattefossé (Lyon, France);

b Merck KGaA (Darmstadt, Germany);

c BASF (Ludwigshafen, Germany).

Abbreviations: PRE, Precirol^® ATO 5; TRA, Transcutol^® HP; TW80, Tween^® 80; HS15, Solutol^® HS15.

Table 2 Physical characteristics of formulation batches (n=3)

Formulation	Average particle size (nm)	PDI	ZP (mV)	EE (%)
F1	354.5± 14.0	0.455±0.053	−22.7±1.0	59.5±2.3
F2	466.9±7.2	0.568±0.055	−25.3±0.7	67.3±3.1
F3	414.1±39.2	0.584±0.064	−24.2±0.3	65.4±2.5
F4	267.6±5.7	0.467±0.025	−19.6±0.8	57.1±1.8
F5	404.8±21.4	0.528±0.028	−21.7±1.1	70.8±2.0
F6	351.3±4.8	0.355±0.035	−18.9±0.4	64.2±2.6
F7	469.6±18.5	0.429±0.013	−20.6±0.2	63.1±1.9
F8	396.9±9.8	0.445±0.051	−23.8±0.4	69.0±2.1
F9	340.6±6.7	0.457±0.065	−22.6±0.8	66.3±0.4
F10	310.5±15.2	0.499±0.089	−19.3±0.8	64.7±2.3
F11	358.9±23.6	0.636±0.008	−18.8±1.0	72.6±1.3
F12	313.7±15.3	0.562±0.070	−18.7±0.3	70.5±0.6

Abbreviations: PDI, polydispersity index; ZP, zeta potential; EE, entrapment efficiency.

Figure 1 Transmission electron microscope image of itraconazole-loaded nanostructured lipid carriers.

Figure 2 Differential scanning calorimetry analysis for ITZ, Precitol ATO 5, blank NLCs and ITZ-NLCs.

Notes: (A) Itraconazole; (B) Precirol^® ATO 5 (Gattefossé Lyon, France); (C) blank nanostructured lipid carriers; (D) itraconazole-loaded nanostructured lipid carriers.

Abbreviations: ITZ, itraconazole; ITZ-NLCs, itraconazole loaded nanostructured lipid carriers; NLCs, nanostructured lipid carriers.

Figure 3 X-ray diffractogram for ITZ-NLCs, blank NLCs and ITZ.

Notes: (A) Itraconazole-loaded nanostructured lipid carriers; (B) blank nanostructured lipid carriers; (C) itraconazole.

Abbreviations: ITZ, itraconazole; ITZ-NLCs, itraconazole loaded nanostructured lipid carriers; NLCs, nanostructured lipid carriers.

Figure 4 In vitro release profile for ITZ solution and ITZ-NLC formulation batch F12 (n=3).

Abbreviations: ITZ, itraconazole; ITZ-NLC, itraconazole-loaded nanostructured lipid carrier.

Figure 5 In vivo itraconazole concentration in brain (n=3).

Note: *P<0.05.

Abbreviations: ITZ, itraconazole; ITZ-NLC, itraconazole-loaded nanostructured lipid carrier.