Design, characterization and in vivo evaluation of nanostructured lipid carriers (NLC) as a new drug delivery system for hydrochlorothiazide oral administration in pediatric therapy

Figures & data

Table 1. Composition of NLC formulations prepared with Precirol^®ATO5 as solid lipid, with Tween^®80 (NLC₁ serial code) or Pluronic^®F68 (NLC₂ serial code) as Surfactant, and different liquid lipid (Transcutol (A), oleic acid (B) and castor oil (C)), both empty and loaded with hydrochlorothiazide (HCT).

Formulation	Precirol^®ATO5(%w/w)	Surfactant type (%w/w)		Liquid lipid (%w/w)			Water (%w/w)	HCT (mg)
		Tween^®80	Pluronic^®F68	Transcutol	Oleic acid	Castor oil
NLC1A empty	5	1.5	–	0.55	–	–	92.95	–
NLC1A	5	1.5	–	0.55	–	–	92.95	200
NLC1B empty	5	1.5	–	–	0.55	–	92.95
NLC1B	5	1.5	–	–	0.55	–	92.95	200
NLC1C empty	5	1.5	–	–	–	0.55	92.95
NLC1C	5	1.5	–	–	–	0.55	92.95	200
NLC2A empty	5	–	1.5	0.55	–	–	92.95
NLC2A	5	–	1.5	0.55	–	–	92.95	200
NLC2B empty	5	–	1.5	–	0.55	–	92.95
NLC2B	5	–	1.5	–	0.55	–	92.95	200
NLC2C empty	5	–	1.5	–	–	0.55	92.95
NLC2C	5	–	1.5	–	–	0.55	92.95	200

Table 2. Mean particle size, polydispersity index (PDI), zeta potential (ζ), encapsulation efficiency (EE%) and loading capacity (LC%) of different NLC formulations (see Table 1 for their composition).

Formulation	size (nm)	PDI	ζ (mV)	EE%	LC%
NLC1A empty	571.3 ± 30.6	0.30 ± 0.02	−25.2 ± 0.4	–	–
NLC1A	605.6 ± 12.1	0.33 ± 0.05	−29.0 ± 0.5	73.4 ± 2.4	2.9 ± 0.3
NLC2A empty	367.4 ± 2.8	0.29 ± 0.02	−38.7 ± 0.9	–	–
NLC2A	368.4 ± 7.6	0.24 ± 0.03	−40.8 ± 0.3	53.9 ± 0.1	2.1 ± 0.1
NLC1B empty	483.6 ± 23.4	0.49 ± 0.03	−35.0 ± 0.6	–	–
NLC1B	650.6 ± 15.3	0.62 ± 0.13	−37.6 ± 0.5	79.1 ± 0.6	3.2 ± 0.3
NLC2B empty	–^a	–	–	–	–
NLC2B	–	–	–	–	–
NLC1C empty	591.1 ± 22.0	0.42 ± 0.08	−35.3 ± 0.8	–	–
NLC1C	563.3 ± 3.7	0.36 ± 0.03	−31.6 ± 1.6	80.0 ± 0.2	3.2 ± 0.0
NLC2C empty	365.1 ± 1.6	0.24 ± 0.04	−42.4 ± 0.4	–	–
NLC2C	405.4 ± 3.8	0.22 ± 0.02	−38.8 ± 1.4	40.1 ± 3.2	1.6 ± 0.1

^agelification occurred.

Figure 1. HCT in vitro release profiles from drug aqueous suspension or from Tween^®80- and Pluronic^®F68-based NLC formulations containing ricin oil as liquid lipid (NLC_1C and NLC_2C) prepared by the homogenization-ultrasonication method.

Table 3. Mean particle size, polydispersity index (PDI), zeta potential (ζ), Encapsulation Efficiency (EE%) and Loading Capacity (LC%) of different ME-based NLC formulations.

Code	S:Co-S (w/w ratio)	size (nm)	PDI	ζ (mV)	EE%	LC%
NLCI	Tween^®80:Tween^®20	327.6 ± 3.7	0.38 ± 0.03	−25.1 ± 0.3	93.2 ± 0.5	3.7 ± 0.2
	1:4
NLCII	Tween^®80:Solutol^®HS	429.3 ± 11.2	0.39 ± 0.02	−25.0 ± 0.9	86.0 ± 0.3	3.4 ± 0.2
	1:1
NLCIII	Pluronic^®F68:Tween^®20	>1μm	1	–	–	–
	1:2
NLCIV	Pluronic^®F68:Tween^®20	>1μm	1	–	–	–
	1:4

Figure 2. HCT in vitro release profiles from NLC formulations produced by the microemulsion method containing S:Co-S mixtures of Tween®80:Tween®20 at 1:4 w/w ratio (NLC_I) and Tween®80:Solutol®HS at 1:1 w/w ratio (NLC_II) in comparison with the corresponding Tween^®80-based NLC formulations prepared by the homogenization-ultrasonication method (NLC_1C) and simple aqueous suspension.

Figure 3. Diuretic effect expressed in terms of: volume of excreted urine (mL) (A); diuretic activity (ml/100g body weight) (B) and diuretic index (C) after oral administration (drug dose of 10 mg kg⁻¹) of the selected HCT-loaded NLC_I, NLC_II and NLC_1C formulations.