Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles

Figures & data

Table 1 Compositions Of Insulin (INS)-Loaded Solid Lipid Nanoparticles (SLNs)

Formulations	Glyceryl Trimyristate (mg)	Soya Lecithin (mg)	L-Penetratin (mg)	D-Penetratin (mg)
INS-SLNs	60	40	-	-
LP-INS-NPs	60	40	5.6	-
DP-INS-NPs	60	40	-	5.6

Note: Each data point represents the mean±SEM (n=3).

Table 2 Particle Characterization Of Insulin (INS)-Loaded Solid Lipid Nanoparticles (SLNs)

Formulations	Size (nm)	PDI	ZP (mV)	EE (%)	DL (%)
INS-SLNs	618.5±8.4	0.734	−17.0±1.53	59.03±4.21	1.64±0.05
LP-INS-SLNs	745.3±12.6	0.227	−23.7±2.13	67.42±3.12	1.82±0.12
DP-INS-SLNs	973.0±15.3	0.710	−20.9±1.63	59.97±5.37	1.62±0.09

Note: Each data point represents the mean±SEM (n=3).

Figure 1 Comparative DSC spectra of insulin (INS)-loaded solid lipid nanoparticles (SLNs).

Figure 2 Comparative FTIR spectra of insulin (INS)-loaded solid lipid nanoparticles (SLNs).

Figure 3 Release profile of INS from different SLNs in simulated gastric fluid (pH 1.2). Each data point represents the mean±SEM (n=3).

Figure 4 Release profile of INS from different SLNs in simulated intestinal fluid (pH 7.4). Each data point represents the mean±SEM (n=3).

Table 3 Elimination Constant And Half-Life Of Insulin (INS) Solution And INS-Loaded Solid Lipid Nanoparticles (INS-SLNs) In Rat Intestinal Fluid

Formulations	kel (×10^−2 min^−1)	t1/2 (min)
INS solution	3.4±0.35	20.1±1.5
INS-SLNs	2.7±0.25	25.2±2.3
LP-INS-SLNs	2.4±0.99	28.1±3.6
DP-INS-SLNs	0.5±0.02^*,#,†	136.7±15.3^*,#,†

Notes: Data: mean±SEM (n=3). *p<0.05: Significantly different than “INS solution” for each measurement, ^#p<0.05: Significantly different than “INS-SLNs” for each measurement. ^†p<0.05: Significantly different than “LP-INS-SLNs” for each measurement.

Figure 5 Degradation profile of INS solution (10 IU/mL) and INS-SLNs over time in rat intestinal fluid. Each data point represents the mean±SEM (n=3).

Figure 6 Blood glucose (A) and serum insulin (B) concentration vs time profiles following oral administration of INS solution (10 U/kg) and INS-SLNs. Each data point represents the mean±SEM (n=5).

Table 4 Pharmacokinetic And Pharmacodynamic Parameters In Rats Following Oral Administration Of Insulin (INS) Solution And INS-Loaded Solid Lipid Nanoparticles (SLNs)

Formulations	Cmax (μU/mL)	Tmax (h)	AAC (% glu. reduc. h)	AUC (μU. h/mL)	PA (%)	BA (%)
INS solution	4.0±0.9	2.6±0.5	5.9±1.2	12.4±1.8	0.3±0.0	0.6±0.0
INS-SLNs	188.9±3.4**	1.0±0.0**	125.3±8.2**	207.6±4.1**	7.5±0.4**	10.9±0.2**
LP-INS-SLNs	624.7±27.4^**,##,††	0.6±0.1^**,##,††	217.5±6.0^**,##,††	295.9±31.0^**,##,††	13.1±0.3^**,##,††	15.7±1.6^**,##,††
DP-INS-SLNs	136.0±35.3**	2.0±0.0*	78.9±8.8**	109.6±32.5**	4.7±0.4**	5.7±1.7**

Notes: Each value represents the mean±SEM (n=5). *p<0.05, **p<0.01, significantly different than “INS solution.” ^##p<0.01, significantly different than “INS-SLNs.” ^††p<0.01, significantly different than “DP-INS-SLNs.”

Abbreviations: Cmax, maximum concentration; Tmax, time to reach Cmax; AAC, area above the curve; AUC, area under the curve; PA, relative pharmacological availability compared with s.c.; BA, relative bioavailability compared with s.c.