Tat peptide-admixed elastic liposomal formulation of hirsutenone for the treatment of atopic dermatitis in NC/Nga mice

Figures & data

Figure 1 Solubilities of HST in DENA solutions at 20°C. Arrow indicates a sufficient solubility of HST to maintain the sink conditions in the receptor phase of the skin permeation study.

Note: Values represent mean ± standard deviation, n = 3.³⁴

Abbreviations: HST, hirsutenone; DENA, N,N-diethylnicotinamide.

Table 1 Permeation parameters of HST in various formulations through depilated mouse skin (mean ± standard deviation, n = 3)

	CC	CC/T	EL	EL/T
Jss (μg/h/cm^2)a	4.88 ± 0.49	7.37 ± 1.55	13.33 ± 1.69	22.63 ± 1.62
Permeated (%)b	3.80 ± 0.45	5.74 ± 1.32	8.99 ± 1.18	15.48 ± 1.31
TL (h)c	2.12 ± 0.34	2.13 ± 0.69	4.92 ± 0.41	4.83 ± 0.28

a Notes: Flux was obtained from the slope of the permeation profile in Figure 2;

b Calculated from the cumulative amount permeated at 24 hours divided by the amount of drug loaded into the samples;

c Lag time calculated from the X-intercept of the linear portion.

Abbreviations: HST, hirsutenone; CC, conventional cream; CC/T, Tat-admixed CC; EL, elastic liposomes; EL/T, Tat-admixed EL.

Figure 2 Permeation profiles of HST in various formulations through depilated mouse skin for 24 hours.

Note: Values represent mean ± standard deviation, n = 3.³⁴

Abbreviations: CC, conventional cream; CC/T, Tat-admixed conventional cream; EL, elastic liposomes; EL/T, Tat peptide-admixed elastic liposomes.

Figure 3 Comparison of formulation effects on skin permeation of HST based on two variables of EL formulation and Tat peptide addition. Enhancement ratio was expressed as a relative ratio of the flux values.

Note: Data are expressed as mean ± standard deviation, n = 3.³⁴

Abbreviations: CC, conventional cream; EL, elastic liposomes; EL/T, Tat peptide- admixed elastic liposomes; HST, hirsutenone.

Figure 4 Clinical observations of atopic dermatitis-like skin lesions in NC/Nga mice after topical administration of various formulations: drug-free cream base (control), Tat-admixed conventional cream (CC/T), and Tat-admixed elastic liposomes (EL/T).³⁴

Figure 5 Changes in skin severity score after topical application of HST formulations: control, CC/T and EL/T. A total score for skin severity was defined as the sum of the individual scores, graded as 0 (none), 1 (mild), 2 (moderate), and 3 (severe), for each sign and symptom, such as erythema, edema, oozing or crust, excoriation, lichenification and dryness.

Notes: Bar represents standard deviation (n = 3), and the statistical analysis was performed using the t-test (*P < 0.05 versus control; **P < 0.05 versus CC/T).³⁴

Abbreviations: CC/T, Tat-admixed conventional cream; EL/T, Tat peptide-admixed elastic liposomes; HST, hirsutenone.

Figure 6 Alterations of (A) iNOS and (B) COX-2 levels in NC/Nga mouse skin after topical application of HST formulations: control, CC/T and EL/T.

Notes: The levels were determined by Western blotting. Bar represents SD (n = 3), and the statistical analysis was performed using the t test (*P < 0.05 versus control;

**P < 0.05 versus CC/T).³⁴

Abbreviations: CC/T, Tat-admixed conventional cream; EL/T, Tat peptide-admixed elastic liposomes; HST, hirsutenone.

Figure 7 Changes in IL-4, IL-13, IgE and eosinophil levels in NC/Nga mouse blood after topical application of HST formulations: control, CC/T and EL/T. Bar graphs represent the levels before the treatment (empty) and 4 weeks after the treatment (filled). (A) The serum IL-4 levels as measured using an ELISA kit; (B) The serum IL-13 levels as measured using an ELISA kit; (C) the serum IgE levels as measured using an ELISA kit; (D) blood eosinophil number as counted by the microscopic differential count.

Note: Bar represents standard deviation (n = 3), and the statistical analysis was performed using the t test (*P < 0.05 versus control).³⁴

Abbreviations: CC/T, Tat-admixed conventional cream; EL/T, Tat peptide-admixed elastic liposomes; HST, hirsutenone.

KangMJEumJYJeongMSFacilitated skin permeation of oregonin by elastic liposomal formulations and suppression of atopic dermatitis in NC/Nga miceBiol Pharm Bul2010331100106

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