Insulin-loaded alginic acid nanoparticles for sublingual delivery

Figures & data

Figure 1. Scanning electron microscopy (SEM) images of insulin-loaded alginic acid nanoparticles.

Table 1. Physico-chemical properties of insulin-loaded alginic acid nanoparticles with/without nicotinamide.

Formulation	Particle size (nm)	Polydispersity index	Entrapment efficiency (%)	Zeta potential	Bioadhesive force (N)	Ratio of molar ellipticity as 208/222
Insulin solution	–	–	–	–	0.005 ± 0.025	1.1
Alginic acid nanoparticles	210 ± 2.4 nm	0.15 ± 0.3	96 ± 5.5 %	−32 ± 2.5	0.423 ± 0.15	1.2
Alginic acid nanoparticles  with nicotinamide	225 ± 3.5 nm	0.23 ± 0.4	97 ± 3.3 %	−30 ± 3.6	0.436 ± 0.23	1.1

Figure 2. FTIR spectra of (a) alginic acid, (b) insulin and (c) alginic acid nanoparticles of insulin.

Figure 3. Thermograms of (a) insulin, (b) alginic acid, and (c) insulin nanoparticles.

Figure 4. Stability of insulin nanoparticles at the end of 12 months evaluated by (a) CD spectra, (b) drug content (c) particle size.

Figure 5. Effect of single administration of insulin on (a) serum insulin level and (b) serum glucose level in streptozotocin-induced diabetic rats, (—•—) insulin solution (subcutaneous-1 IU/kg), (—♦—) insulin nanoparticles (sublingual-5 IU/kg), (—▴—) insulin nanoparticles with nicotinamide and (—×—)blank nanoparticles with nicotinamide (n = 6).

Table 2. Pharmacodynamic and pharmacokinetic parameters obtained by administration of insulin solution or nanoparticles to the diabetic rats.

Formulation	Subcutaneous injection	Sublingual alginic acid nanoparticles	Sublingual alginic acid nanoparticles-nicotinamide
Insulin dose (IU/kg)	1	5	5
Maximum reduced glucose level (%)	68.2 ± 2.3	38.1 ± 4.2	49.2 ± 1.3
Time point of maximum reduced glucose level (h)	2	2	2
AAC	562.3 ± 1.6	559.3 ± 4.2	691.2 ± 6.3
PA	–	100.2 ± 4.9	125.1 ± 5.7
Cmax (µIU/mL)	97.2 ± 2.1	17.4 ± 2.1	25.3 ± 3.4
tmax (h)	1	2	2
AUC0→24/rat	244.3 ± 7.1	201. ± 5.5	292.2 ± 4.3
BA (%)	–	80.1 ± 2.5	96.3 ± 2.1

Each data represents the mean ± SD (n = 4).

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

Figure 6. Light micrographs of the sublingual rat mucosal membranes following administration of INS-NPs (5 IU/kg) containing nicotinamide (a) and distilled water as control (b).