Microneedle-mediated transdermal delivery of nanostructured lipid carriers for alkaloids from Aconitum sinomontanum

Figures & data

Figure 1. SEM images of (A) microneedles and (B) skin from the control and MN-treated nude mice.

Figure 2. In vitro skin permeation profiles of LA and RAN from AAS–NLCs and a physical mixture of AAS and blank NLCs applied to the MN-treated skin and AAS–NLCs applied to the untreated skin (n = 3).

Figure 3. Analysis of NLC transport upon using MNs. (A) NanoSight image of a skin sample treated with MNs and C6-NLCs, (B) laser scanning confocal microscopy images of an untreated nude mouse skin after administration of C6-NLCs (NLCs), MN-treated skin after application of a mixture of C6 and blank NLCs (Mixture-MN), and MN-treated skin after application of C6-NLCs (NLCs-MN).

Figure 4. Representative mean plasma concentration–time profiles of (A) LA and (B) RAN after percutaneous and hypodermic applications (n = 5).

Table 1. Pharmacokinetic parameters of LA released from AAS–NLCs in rats by transdermal treatment with or without microneedles and subcutaneous injection.

Parameter	i.h. (0.3 mL)	NLCs (0.3 mL)	NLCs (1 mL)	NLCs–MN (0.3 mL)	NLCs–MN (1 mL)
Tmax (h)	0.50 ± 0.00	6.40 ± 0.89	6.00 ± 2.00	6.00 ± 2.00	6.00 ± 2.00
Cmax (ng/mL)	97.26 ± 29.18	4.13 ± 1.18*	7.00 ± 2.81*	20.55 ± 9.22*,#	47.00 ± 16.84*,#
MRT0–t (h)	3.58 ± 1.41	17.42 ± 2.23*	18.22 ± 2.47*	13.05 ± 1.83*	13.50 ± 1.89*
AUC0–t (ng/mL × h)	139.62 ± 28.67	88.60 ± 23.74	154.94 ± 63.73	215.45 ± 43.47#	599.37 ± 192.58*,#

Mean ± SD, n = 5.

* p < .05 vs. i.h..

# p < .05 NLCs-MN vs. NLCs.

Table 2. Pharmacokinetic parameters of RAN released from AAS–NLCs in rats by transdermal treatment with or without microneedles and subcutaneous injection.

Parameter	i.h. (0.3 mL)	NLCs (0.3 mL)	NLCs (1 mL)	NLCs–MN (0.3 mL)	NLCs–MN (1 mL)
Tmax (h)	0.50 ± 0.00	7.20 ± 3.03	5.20 ± 2.28	5.60 ± 0.89	5.60 ± 1.67
Cmax (ng/mL)	18.91 ± 2.70	1.15 ± 0.18*	2.14 ± 1.01*	3.50 ± 1.59*,#	8.45 ± 4.86*,#
MRT0–t (h)	16.77 ± 0.63	22.98 ± 0.41*	21.52 ± 1.67*	18.99 ± 2.46	15.52 ± 2.46
AUC0–t (ng/mL × h)	55.92 ± 2.81	41.15 ± 1.25	46.89 ± 8.50	63.99 ± 21.70#	115.94 ± 40.26*,#

Mean ± SD, n = 5.

* p < .05 vs. i.h.

# p < .05 NLCs-MN vs. NLCs.

Figure 5. Effects of different administration modes on (A) toe volumes, (B) organ indexes and (C) appearances and histopathological examinations of ankle joints in rats. Inflammatory infiltration areas are marked, **p < .01, *p < .05 compared with the model group (n = 8).

Figure 6. Effects of different treatments on serum levels of inflammatory and pain factors in rats. **p < .01, *p < .05 compared with the model group (n = 8).

Figure 7. Irritation responses on the surface and microstructure of the rabbit back skin. The skin was treated with (A) blank NLCs; (B) AAS–NLCs; (C) combination of AAS–NLCs and MNs; (a) with drugs applied; (w) with drugs washed off. Magnification: 100×.

Figure 8. Representative ECG results for rats after percutaneous and hypodermic applications.