Repaglinide-loaded nanostructured lipid carriers with different particle sizes for improving oral absorption: preparation, characterization, pharmacokinetics, and in situ intestinal perfusion

Figures & data

Table 1. Characterization of REP-NLCs-Small, REP-NLCs-Large, and corresponding blank NLCs (mean ± SD, n = 3).

Nanoparticles	Particle size (nm)	PDI	Zeta potential (mV)	Encapsulation efficiency (%)	Drug loading (%)
Blank NLCs-Large	351.0 ± 16.55	0.223 ± 0.171	–3.49 ± 1.50	–	–
Blank NLCs-Small	76.90 ± 2.613	0.260 ± 0.007	–10.2 ± 2.08	–	–
REP-NLCs-Large	325.3 ± 6.090	0.152 ± 0.083	–10.9 ± 2.35	98.60 ± 0.26	3.05 ± 0.01
REP-NLCs-Small	79.83 ± 3.895	0.275 ± 0.004	–12 ± 2.89	96.83 ± 0.55	4.41 ± 0.003

Figure 1. Characterization of NLCs. The particle sizes and PDI changes of REP-NLCs-Small and REP-NLCs-Large in pH 1.2 hydrochloric acid solution (A), pH 6.8 phosphate buffer (B), pH 7.4 phosphate buffer (C), SGF (D), SIF (E), FBS for 24 h (F), and at 4 °C for 7 days (G), respectively (mean ± SD, n = 3). The TEM images of REP-NLCs-Small (H) and REP-NLCs-Large (I), respectively. The in vitro release profiles of REP-NLC-Small, REP-NLC-Large and REP-Sol (J, mean ± SD, n = 3).

Figure 2. The mean plasma concentration–time curves of REP-NLCs-Small, REP-NLCs-Large, and REP-marketed tablets by orally administrated 1.28 mg/kg of repaglinide in rats (mean ± SD, n = 4).

Table 2. Pharmacokinetic parameters in each group.

Parameters	Marketed tablets	NLC-Large	NLC-Small
AUC0–12 (μg/l·h)	355.717 ± 55.992	685.899 ± 92.459**	1073.958 ± 175.391**
Cmax (μg/l)	195.1 ± 84.217	523.125 ± 94.500**	702.8 ± 38.988**
T1/2 (h)	6.148 ± 3.612	5.336 ± 3.927	3.401 ± 1.26
Tmax (h)	0.27 ± 0.158	0.27 ± 0.04	0.33 ± 0.000

^** p< .01 for REP-NLCs-Large versus REP-marketed tablets and REP-NLCs-Small versus REP-NLCs-Large and (mean ± SD, n= 4).

Figure 3. The K_a (A) and P_eff (B) obtained from in situ single-pass intestinal perfusion of REP-NLCs-Small, REP-NLCs-Large, and REP-Sol in duodenum, jejunum, ileum, and colon in rats (means ± SD, n = 3, *p<.05, **p<.01).

Figure 4. Schematic presentation of the mucus layer, intestinal epithelial cells layer and the transport routes of NLCs with different particles size.