Trans-resveratrol-loaded nonionic lamellar liquid-crystalline systems: structural, rheological, mechanical, textural, and bioadhesive characterization and evaluation of in vivo anti-inflammatory activity

Figures & data

Figure 1 Schematic representation of lamellar, hexagonal, and cubic liquid-crystal mesophases formed by surfactant-molecule self-assembly.

Figure 2 Ternary-phase diagram of copaiba oil as the oily phase (O), hydrogenated castor oil as the surfactant (S), and water (W).

Note: Red points indicate the selected formulations.

Abbreviations: PS, phase separation; VSs, viscous systems; TLSs, transparent liquid systems.

Table 1 Composition of the studied formulations

Formulation	Content (%)
	Oil phase	Aqueous phase	Surfactant
CB-23	40	20	40
CB-24	30	30	40
CB-25	20	40	40

Figure 3 Characterization of the liquid-crystalline dispersions.

Notes: (A) Macroscopic appearance, (B) photomicrographs obtained by polarized light microscopy (figures were obtained at 40× magnification and the enlarged area at 250× magnification), and (C) small-angle X-ray scattering patterns of the samples.

Table 2 Peak positions (q) of the SAXS curves, interplanar distances (d), and classification of formulations

Formulation	Peak positions q (1/nm^−1)				Peak ratios			d (nm)	Mesophase
	q1	q2	q3	q4	d2:d1	d3:d2	d4:d1
CB-23	0.47	0.95	–	–	2.0	–	–	14.8	Lamellar
CB-24	0.32	0.42	0.86	1.29	1.31	2.0	4.0	19.6	Lamellar/hexagonal
CB-25	0.32	0.43	0.86	1.29	1.31	2.0	4.0	19.6	Lamellar/hexagonal

Abbreviation: SAXS, small-angle X-ray scattering.

Table 3 Flow index (n) and consistency index (k) of all formulations obtained from the power law (n=3)

Formulations	n	k (Pa s^n)
CB-23	0.019±0.011	472.270±20.044
CB-23R	0.369±0.026	98.264±10.429
CB-24	0.287±0.012	301.222±15.235
CB-24R	0.645±0.023	58.965±5.685
CB-25	0.826±0.013	2.392±0.136

Figure 4 Flow rheograms of unloaded and Res-loaded formulations.

Notes: (A) Flow rheograms of unloaded formulations; (B) flow rheograms of Res-loaded formulations. The closed symbols represent up curves, and open symbols represent down curves. The standard deviations were omitted for clarity; however, in all cases, coefficients of variation of triplicate analyses were less than 10%. Analysis was carried out at 32°C±0.5°C.

Abbreviation: Res, resveratrol.

Table 4 Mechanical and bioadhesion properties of the loaded and unloaded formulations (n=3)

Formulation	Mechanical parameters				Bioadhesive force (mN)
	Hardness (mN)	Compressibility (mN/s)	Adhesiveness (mN/s)	Cohesiveness (dimensionless)
CB-23	599.7±25.0^a,c	8,225.0±210.9^d,f	6,590.8±284.6^g,i	0.817±0.044	94.972±5.646^j,l,m
CB-23R	361.3±51.4^a,c	4,932.3±75.7^d,f	2,234.6±71.3^g,i	0.752±0.004	80.565±5.551^j,l,m
CB-24	188.3±10.1^b,c	2,369.7±227.6^e,f	1,627.5±73.9^h,i	0.826±0.034	38.648±1.880^k,l,m
CB-24R	86.0±1.0^b,c	1,366.3±70.8^d,f	910.7±3.5^h,i	0.737±0.052	20.303±0.319^k,l,m
CB-25	*	*	*	*	5.524±0.062^l
CB-25R	*	*	*	*	5.021±0.108^m

Notes:

* It was not possible to collect these data. The same superscript letters indicate statistically significant differences between the means (P<0.05).

Figure 5 Anti-inflammatory activity of Res-loaded formulations (CB-23R and CB-24R).

Notes: Res-unloaded formulations served as the vehicle, an ointment containing dexamethasone 0.5% (w:w) was used as the positive control, and untreated mice were considered the negative control. Data represent means ± standard deviation of five mice. The statistical significance of the differences in paw thickness between the groups was analyzed using analysis of variance followed by Dunnett’s multiple-comparison test. **P<0.01; ^#no significance.

Abbreviation: Res, resveratrol.