Solid lipid nanoparticles modified with stearic acid–octaarginine for oral administration of insulin

Figures & data

Table 1 DL, EE, average diameter, PDI, and zeta potential of Ins-SLNs and SA-R₈-Ins-SLNs

Sample	DL% of insulin	EE% of insulin	DL% of SA-R8	EE% of SA-R8	Diameter (nm)	PDI	ζ* (mV)
Ins-SLNs	3.09 ± 0.45	64.89 ± 3.55	–	–	137.4 ± 12.19	0.21 ± 0.07	−32.13 ± 1.05
SA-R8-Ins-SLNs	3.19 ± 0.32	76.54 ± 2.18	11.74 ± 1.54	93.92 ± 3.32	162.4 ± 15.23	0.14 ± 0.02	29.87 ± 4.53

Notes: Mean ± SD, n = 3.

* ζ, zeta potential.

Abbreviations: DL, drug loading; EE, encapsulation efficiency; Ins-SLNs, Ins-SLNs, insulin solid lipid nanoparticles; PDI, polydispersity index; SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine; SD, standard deviation.

Figure 1 Transmission electron microscopic (TEM) images of SA-R₈-Ins-SLNs.

Abbreviation: SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine.

Figure 2 The remaining ratio of insulin after the incubation in SGF with pepsin.

Abbreviations: Ins-SLNs, insulin solid lipid nanoparticles; SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine; SGF, simulated gastric fluid.

Figure 3 Remaining ratio of insulin after incubation in SIF with trypsin.

Abbreviations: Ins-SLNs, insulin solid lipid nanoparticles; SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine; SIF, simulated intestinal fluid.

Table 2 Apparent permeability coefficient (P_app) and absorption enhancement ratio (R) for insulin across Caco-2 cell monolayers

Sample	Papp (×10^−6 cm/s)*	R
Insulin solution	0.52 ± 0.09	–
Ins-SLNs	1.17 ± 0.14	2.25
SA-R8-Ins-SLNs	9.59 ± 0.10	18.44

Notes: n = 6.

* Data were expressed as mean ± SD of three experiments.

Abbreviations: Ins-SLNs, insulin solid lipid nanoparticles; SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine; SD, standard deviation.

Figure 4 Blood glucose levels changes after subcutaneous or duodenal administration to STZ-diabetic rats. (A) subcutaneous administration of insulin (2 IU/kg); (B) insulin standard solution (25 IU/kg); (C) duodenum administration of Ins-SLNs (25 IU/kg); (D) SA-R₈-Ins-SLNs (25 IU/kg).

Abbreviations: Ins-SLNs, insulin solid lipid nanoparticles; SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine; STZ, streptozocin.

Table 3 The relative pharmacological availability of both SLNs

Sample	AAC (%)	PA (%)
Insulin solution (25 IU/kg)	10.05 ± 4.32	0.42 ± 0.72
Subcutaneous administration of insulin (2 IU/kg)	189.75 ± 5.79	100
Ins-SLNs (25 IU/kg)	100.70 ± 5.08	4.28 ± 0.84
SA-R8-Ins-SLNs (25 IU/kg)	328.78 ± 4.76	13.86 ± 0.79

Abbreviations: AAC, area above the glucose reduction–time curve; Ins-SLNs, insulin solid lipid nanoparticles; PA, pharmacological availability; SA-R₈-Ins-SLNs, insulin solid lipid nanoparticles modified with stearic acid–octaarginine.