Fig 1.
Particle size frequency and image of IMC-MP@GCgel and IMC-NP@GCgel.
(A) and (B) Particle size distribution data of the IMC-MP@GCgel (A) and IMC-NP@GCgel (B) determined using SALD-7100. (C) Particle size distribution of the IMC-NP@GC gel using NanoSight LM10. (d) Digital images of IMC-MP@GCgel and IMC-NP@GCgel. The particle size was significantly reduced by bead milling with GA, and the mean particle size of the IMC-NP@GCgel was 40–200 nm.
Fig 2.
XRD and TG-DTA patterns of IMC-MP@GCgel and IMC-NP@GCgel.
(A) XRD pattern of IMC powder. (B) Changes in XRD pattern of vehicle, IMC-MP@GCgel and IMC-NP@GCgel. (C) TG and DTA pattern of IMC powder. (D) and (E) Changes in TG (D) and DTA pattern (E) of vehicle, IMC-MP@GCgel and IMC-NP@GCgel. No difference in the XRD and TG-DTA patterns were observed in IMC-MP@GCgel and IMC-NP@GCgel.
Fig 3.
Non-uniformity (A), solubility (B), and viscosity (C) of IMC-MP@GCgel and IMC-NP@GCgel.
n = 5. *P < 0.05 vs. IMC-MP@GCgel for each category (Student’s t-test). The uniformity and solubility of IMC in IMC-NP@GCgel were higher than those in IMC-MP@GCgel. However, the viscosity of IMC was similar in the IMC-MP@GCgel and IMC-MP@GCgel.
Table 1.
Evaluation of formulation safety and stability of IMC-MP@GCgel and IMC-NP@GCgel.
Table 2.
Pharmacokinetic analysis of IMC@GCgel in in vitro skin penetration.
Table 3.
Pharmacokinetic analysis of percutaneous absorption of the IMC@GCgel.
Fig 4.
Release behavior of IMC from IMC-MP@GCgel and IMC-NP@GCgel through a 450-nm pore membrane.
(A) and (B) Drug release (A) and AUC0-24h release (B) from the IMC-MP@GC gel and IMC-NP@GC gel. (C) and (D) Number (C) and size distribution (D) of IMC NPs in the reservoir chamber 24 h after the application of IMC-NP@GCgel. n = 5. N.D., not detectable. *P < 0.05 vs. IMC-MP@GCgel (repeated-measures ANOVA). #P < 0.05 vs. IMC-MP@GCgel for each category (Student’s t-test). Drug release from the IMC-NP@GC gel was higher than that from the IMC-MP@GCgel, and IMC NPs (40–430 nm) were detected in the reservoir chamber after application of the IMC-NP@GCgel.
Fig 5.
Changes in in vitro transdermal penetration of IMC from IMC-MP@GCgel and IMC-NP@GCgel through a rat skin.
(A) and (B) Transdermal penetration (A) and AUC0–24 release (B) of IMC-MP@GCgel and IMC-NP@GCgel (in vitro study). n = 5. *P < 0.05 vs. IMC-MP@GCgel (repeated-measures ANOVA). #P < 0.05 vs. IMC-MP@GCgel for each category (Student’s t-test). Drug penetration from the IMC-NP@GCgel was higher than that from the IMC-MP@GCgel. In contrast to the result obtained for the release of IMC from the IMC-NP@GCgel, IMC NPs were not detected in the reservoir chamber after application.
Fig 6.
Changes in IMC levels in blood and skin tissue of rat treated with IMC-MP@GCgel and IMC-NP@GCgel.
(A) Plasma IMC levels in rats 24 h after treatment with IMC-MP@GCgel and IMC-NP@GCgel. (B) IMC content in the skin tissue of rats 6 h after treatment with IMC-MP@GCgel and IMC-NP@GCgel. n = 5. *P < 0.05 vs. IMC-MP@GCgel for each category (student’s t-test). IMC levels in the skin tissue of rats treated with the IMC-NP@GCgel were higher than those treated with the IMC-MP@GCgel. However, the plasma IMC levels were not difference between IMC-MP@GCgel- and IMC-NP@GCgel-treated rats.
Fig 7.
Scheme for absorption after treatment with IMC-MP@GCgel and IMC-NP@GCgel in the rat skin.