Transdermal absorption enhancement of gel containing elastic niosomes loaded with gallic acid from Terminalia chebula galls

Figures & data

Figure 1.  The gradient high-performance liquid chromatography (HPLC) chromatogram of (A) cold water crude extract of Terminalia chebula galls containing phenolic compounds including gallic acid (1), 1,3,6-tri-O-galloyl-ß-d-glucopyranose (2), punicalagin (3), isoterchebulin (4), chebulagic acid (5), and chebulinic acid (6) and (B) the semipurified fraction.

Table 1.  Percentage yields and total phenolic contents of fractions by column chromatography from the cold aqueous Terminalia chebula gall crude extract.

Column	Fraction no.	Eluting solvent	Eluting solvent ratio	% Yield of the fraction	Total phenolic contents (mg GAE/g)
Dianion	—	MeOH/H2O	1:1	34.76	36.90 ± 0.37
ODS	F1	MeOH/H2O/AcOH	2:8:0.1	6.75	21.43 ± 1.31
	F2	MeOH/H2O/AcOH	4:6:0.1	9.25	7.67 ± 2.98
	F3	MeOH/H2O/AcOH	6:4:0.1	6.25	2.81 ± 0.06

Note: The total phenolic content was expressed in mg of gallic acid equivalents (GAEs) per 100 g of the crude extract. The calibration equation for gallic acid was y = 7.8829x + 0.0477 (r² = 0.9994).

Table 2.  Size, entrapment efficiency, zeta potential, and deformability index (DI) of nonelastic and elastic niosomes loaded with gallic acid or the semipurified fraction containing gallic acid.

Formulations	Initial size (nm)	Size after filtration (nm)	% Entrapment efficiency of gallic acid	Zeta potential	Deformability index (DI)
Nonelastic niosomes
Blank	214.40 ± 10.41	85.71 ± 11.91	—	−38.50 ± 2.58	2.79 ± 0.34
Loaded with gallic acid	235.07 ± 7.43	47.45 ± 6.72	29.72 ± 1.68	−46.64 ± 0.78	2.50 ± 0.78
Loaded with the semipurified fraction	395.95 ± 31.69	77.00 ± 13.18	20.10 ± 3.91	−47.11 ± 0.73	2.04 ± 1.13
Elastic niosomes
Blank	146.57 ± 11.19	139.22 ± 21.18	—	−32.76 ± 1.13	11.36 ± 1.55
Loaded with gallic acid	171.15 ± 4.03	115.79 ± 3.38	55.18 ± 3.87	−35.55 ± 0.31	10.98 ± 2.75
Loaded with the semipurified fraction	230.13 ± 56.69	96.08 ± 32.88	24.34 ± 1.53	−44.56 ± 1.89	10.75 ± 3.47

Values represent mean ± SD (n = 3).

Figure 2.  Negative-staining TEM images of elastic and nonelastic niosomes (Tween 61 mixed with cholesterol at 1:1 molar ratio, 20 mM) loaded with gallic acid and the semipurified fraction containing gallic acid: (A) elastic niosomes loaded with gallic acid (GE) (×15,000); (B) nonelastic niosomes loaded with gallic acid (GN) (12,000×); (C) elastic niosomes loaded with the semipurified fraction (SE) (15,000×); and (D) nonelastic niosomes loaded with the semipurified fraction (SN) (15,000×).

Figure 3.  The percentages of gallic acid remaining in various formulations at different storage temperatures (27 ± 2, 4 ± 2, and 45 ± 2°C) for 3 months. GS = gallic acid in phosphate buffer solution; GE = elastic niosomes loaded with gallic acid; GN = nonelastic niosomes loaded with gallic acid; SS = the semipurified fraction in phosphate buffer solution; SE = elastic niosomes loaded with the semipurified fraction; SN = nonelastic niosomes loaded with the semipurified fraction.

Figure 4.  Cumulative amounts (µg/cm²) of gallic acid from various gel formulations versus time (hours) in stratum corneum (SC) (A), viable epidermis and dermis (VED) (B) and receiving solution (C) following transdermal absorption across excised rat skin by vertical Franz diffusion cells.

 = GS; gallic acid in phosphate buffer solution;

 = GE; elastic niosomes loaded with gallic acid;

 = GN; nonelastic niosomes loaded with gallic acid;

 = SS; the semipurified fraction in phosphate buffer solution;

 = SE; elastic niosomes loaded with the semipurified fraction;

 = SN; nonelastic niosomes loaded with the semipurified fraction.

Table 3.   The percentages of gallic acid amounts (%) in stratum corneum (SC), viable epidermis and dermis (VED), and receiving solution following transdermal absorption across excised rat skin from various gel formulations by Franz diffusion cells after 12 h.

Gel formulations containing	Percentages of gallic acid amount (%)
	SC	VED	Receiving solution
Gallic acid in phosphate buffer solution (GS)	35.96 ± 7.59	0.87 ± 0.14	0.64 ± 0.19
Elastic niosomes loaded with gallic acid (GE)	32.86 ± 9.94	0.35 ± 0.10	0.21 ± 0.08
Nonelastic niosomes loaded with gallic acid (GN)	33.51 ± 8.60	0.27 ± 0.02	0.14 ± 0.04
Semipurified fraction in phosphate buffer solution (SS)	41.01 ± 8.90	0.19 ± 0.06	0.09 ± 0.03
Elastic niosomes loaded with the semipurified fraction (SE)	32.92 ± 3.42	0.70 ± 0.15	0.37 ± 0.14
Nonelastic niosomes loaded with the semipurified fraction (SN)	33.99 ± 2.70	0.33 ± 0.07	0.22 ± 0.01

Values represent mean ± SD (n = 3).

Note: GS, GE, and GN gel containing 0.5% w/w gallic acid, and SS, SE, and SN gel containing the semipurified fraction with 0.08% w/w of gallic acid.

Percentages of gallic acid amount (%) = (gallic acid amounts found in SC, VED, or receiving solution/the total gallic acid in 0.5 g of each gel formulation) × 100.