Cubosomal Betamethasone-Salicylic Acid Nano Drug Delivery System for Enhanced Management of Scalp Psoriasis

Figures & data

Table 1 Independent and Dependent Variables for Preparing BD/SA Cubosomal Dispersion

Independent Variables (as % of Dispersed Phase)			Optimization Goal		Expected	Observed	Residual
	Low	High
GMO	80	97.5	Particle size (nm)	Minimize	170.743	197.4	−26.657
P407	2.5	19.5	Zeta potential (mv)	Maximize	−31.49	−44.4	12.91
SCMC	0	5	Viscosity (cp)	Maximize	3251.68	1529.632	1722.048
			BD content %	——-	112.337	105.85	6.487
			SA content %	——-	132.072	88.85	43.22

Table 2 Different Compositions of 0.064% BD 2% SA Loaded Cubosomes Dispersed Phase

Run	Percent of the Dispersed Phase %
	GMO	P407	SCMC
1	80	20	0.55
2	93.125	6.875	0.775
3	88.75	11.25	0.55
4	80	20	0.1
5	97.5	2.5	0.1
6	88.75	11.25	0.1
7	88.75	11.25	1
8	88.75	11.25	0.55
9	80	20	1
10	84.375	15.625	0.325
11	88.75	11.25	1
12	97.5	2.5	0.55
13	97.5	2.5	1

Table 3 Particle Size, PDI, Zeta Potential, BD/SA Content for the 13 Different Cubosomal Dispersions and OF

Run	Particle Size (nm)	PDI	Zeta Potential (mv)	SA Content (%)	BD Content (%)	Viscosity (cp)
1	142.25±2.757	0.379±0.0127	−22.2±0.141	111.98± 5.300	99.495± 1.209	356.924±23.90
2	511±15.697	0.1545±0.067	−35.95±2.050	106.920±4.150	108.655±3.231	1054.28± 64.80
3	300.25±10.394	0.239±0.076	−33.65±0.919	106.561± 5.381	114.015±1.831	271.442± 15.73
4	195.75±22.273	0.3345±0.068	−21.1±1.555	109.089± 1.468	81.98±2.602	287.939± 32.01
5	300.05±14.919	0.106±0.014	−30.9±0.707	88.560± 2.413	99.27±0.650	14.6969± 2.65
6	500.55±22.839	0.6225±0.067	−12.45±1.909	102.705± 4.600	85.515±1.590	21.1455± 4.89
7	490.2±22.203	0.5945±0.043	−43.25±0.212	111.081± 5.016	116.085±5.324	3554.24± 83.64
8	294.8±24.465	0.4065±0.037	−9.72±1.668	83.789± 2.636	102.123±7.802	271.442± 13.76
9	285.85±0.353	0.444±0.096	−36.1±0.141	101.597±0.841	115.012 ±1.728	2624.44± 106.43
10	170.45±8.273	0.2675±0.012	−21.4±0.707	99.339±1.432	82.022±2.831	208.456± 40.80
11	285.75±30.902	0.462±0.151	−9.465±1.039	100.977±3.652	81.953±1.847	2744.41± 152.52
12	323.1±39.315	0.4765±0.089	−16.35±0.636	102.356±4.813	83.755±0.219	253.446± 12.58
13	475.4±32.244	0.4935±0.033	−52.3±2.121	101.181±2.062	100.50± 2.80	616.368± 62.79
OF	197.4±9.475	0.443±0.025	−44.5±0.141	88.855±2.920	105.855± 3.37	1529.632± 96.82

Figure 1 (A) 3D representation of the effect of different GMO/P407/SCMC concentrations on cubosomes average particle size. (B) Two components mix of the effect of different GMO/P407 concentrations on cubosomes average particle size.

Figure 2 3D representation of the effect of different GMO/P407/SCMC concentrations on single-point viscosity.

Table 4 Rheological Behaviour for the 13 Different Cubosomal Dispersions and OF

Run	Flow Index (n)		Regression Coefficient (r^2)			Type of Flow
			Bingham	Casson	Carreau
1	0.663	Shear thinning	0.9804	0.9828	0.6503	Non-linear plastic
2	0.171	Shear thinning	0.3333	0.4457	0.9497	Pseudo-plastic
3	0.740	Shear thinning	0.9964	0.9992	0.8982	Linear plastic
4	0.319	Shear thinning	0.4799	0.5283	0.9734	Pseudo-plastic
5	0.614	Shear thinning	0.9951	0.9819	0.9495	Linear plastic
6	0.280	Shear thinning	0.7257	0.5907	0.9638	Pseudo-plastic
7	0.591	Shear thinning	0.9909	0.9885	0.9261	Linear plastic
8	0.694	Shear thinning	0.9992	0.9986	0.9684	Non- linear plastic
9	0.782	Shear thinning	0.9949	0.9966	0.9584	Non- linear plastic
10	0.403	Shear thinning	0.9372	0.8695	0.9632	Pseudo-plastic
11	0.524	Shear thinning	0.9718	0.9428	0.8154	Linear plastic
12	0.784	Shear thinning	0.9962	0.9988	0.9157	Non- linear plastic
13	0.460	Shear thinning	0.6544	0.7522	0.8578	Pseudo-plastic
OF	0.852	Shear thinning	0.9804	0.9828	0.6503	Non- linear plastic^a

Note: ^aThe highest calculated r² of each cubosomal dispersion reflecting the run’s rheological flow is underlined and written in bold.

Figure 3 Micrographs by HRTEM shows cubic shaped nanoparticles with edged dimensions with different particle size within the nano-range.

Figure 4 In-vitro release of BD/SA from the OF.

Figure 5 (A) The change in ear thickness over the 7 days of the experimental model. (B) The change in ear thickness in all groups on day 7.

Figure 6 Changes in the right ear pinna receiving IMQ on days (A) 1, (B) 3 and (C) 7.

Figure 7 Psoriasis progression in all groups on days 2, 5 and 7.

Figure 8 Graphical representation of the progression of (A) erythema, (B) thickness, (C) scaling, (D) cumulative PASI score in all groups over the 7 days of the experimental model.

Figure 9 Representative photograph of harvested spleen in all groups on the 7th day of the experimental model. (A) Healthy group, (B) group receiving 5% IMQ only, (C) group receiving 5% IMQ + void cubosomes in 1%SCMC, (D) group receiving 5% IMQ + BD SA cubosomes in 1%SCMC and (E) group receiving 5% IMQ + commercial BD SA lotion.

Figure 10 Spleen to body weight ratio among all groups on the 7th day of the experimental model.

Figure 11 (A) Dorsal skin micrograph of healthy mice under X500um magnification, (B) dorsal skin micrograph of healthy mice under X50um magnification, (C) dorsal skin micrograph of mice receiving 5%IMQ only under X500um magnification, (D) dorsal skin micrograph of mice receiving 5%IMQ only under X50um magnification, (E) dorsal skin micrograph of mice receiving 5%IMQ and void cubosomes in 1%SCMC under X500um magnification, (F) dorsal skin micrograph of mice receiving 5%IMQ and void cubosomes in 1%SCMC under X50um magnification, (G) dorsal skin micrograph of mice receiving 5%IMQ and commercial BDSA lotion under X500um magnification, (H) dorsal skin micrograph of mice receiving 5%IMQ and commercial BDSA lotion under X50um magnification, (I) dorsal skin micrograph of mice receiving 5%IMQ and tested cubosomal BDSA dispersion in 1%SCMC under X500um magnification, (J) dorsal skin micrograph of mice receiving 5%IMQ and tested cubosomal BDSA dispersion in 1%SCMC under X50um magnification.

Figure 12 Average epidermal thickness in all groups at the 7th day of the experiment.