Enhanced dermal delivery of diflucortolone valerate using lecithin/chitosan nanoparticles: in-vitro and in-vivo evaluations

Figures & data

Table 1 Physicochemical properties of nanoparticles

Nanoparticle formulations	IPM	Particle size ± SD (nm)	Zeta potential ± SD (mV)	Polydispersity index ± SD
Blank	–	218.2 ± 15.1	25.1 ± 1.80	0.190 ± 0.05
DFV loaded	–	210.7 ± 10.5	30.4 ± 2.40	0.152 ± 0.03
Blank	X	210.4 ± 11.2	38.3 ± 2.51	0.180 ± 0.04
DFV loaded	X	204.2 ± 10.1	41.4 ± 1.60	0.149 ± 0.02

Abbreviations: DFV, diflucortolone valerate; IPM, isopropyl myristate; SD, standard deviation.

Figure 1 Transmission electron microscopy images of diflucortolone valerate–loaded nanoparticles at magnification ratio of 33,000× (A), at magnification ratio of 71,000× (B).

Figure 2 Differential scanning calorimetry thermograms of pure DFV (A), blank nanoparticles (B), physical mixture of blank nanoparticles and DFV (C), and drug-loaded nanoparticles (D).

Abbreviation: DFV, diflucortolone valerate.

Figure 3 The in-vitro drug-release profile of diflucortolone valerate from nanoparticles (n = 6).

Table 2 Stability results of the nanoparticle formulations

Time (days)	Particle size ± SD (nm)	Zeta potential ± SD (mV)	Polydispersity index ± SD
10	213.4 ± 12.4	35.3 ± 3.2	0.190 ± 0.03
	206.5 ± 6.2	40.8 ± 1.24	0.144 ± 0.04
30	215.6 ± 10.5	33.4 ± 4.5	0.186 ± 0.06
	205.9 ± 4.8	42.4 ± 1.69	0.138 ± 0.01
60	215.9 ± 8.7	34.2 ± 2.8	0.192 ± 0.05
	208.2 ± 8.3	40.8 ± 2.01	0.156 ± 0.03
90	216.5 ± 10.6	32.6 ± 3.5	0.191 ± 0.08
	208.5 ± 10.4	42.2 ± 1.77	0.154 ± 0.04

Note: Grey line for blank nanoparticles.

Abbreviation: SD, standard deviation.

Figure 4 Flow rheograms of chitosan gel formulations – shear rate versus shear stress (n = 3).

Abbreviations: DFV, diflucortolone valerate; Pa, pascal.

Figure 5 The elastic modulus plotted versus frequency of formulations (n = 3).

Abbreviation: DFV, diflucortolone valerate; G′, elastic (storage) modulus.

Table 3 Mechanical properties of formulations

Formulation	Ratio	Hardness (N) ± SD	Compressibility (N · mm) ± SD	Adhesiveness (N · mm) ± SD	Cohesiveness ± SD	Elasticity ± SD
Chitosan gel		0.012 ± 0.001	0.026 ± 0.004	0.018 ± 0.001	0.926 ± 0.052	0.814 ± 0.078
DFV-loaded chitosan gel		0.012 ± 0.002	0.027 ± 0.003	0.016 ± 0.002	0.899 ± 0.046	0.845 ± 0.075
Blank nanoparticle/ chitosan gel	1:1	0.008 ± 0.002	0.019 ± 0.001	0.009 ± 0.001	0.898 ± 0.013	0.813 ± 0.059
	1:3	0.009 ± 0.001	0.021 ± 0.001	0.011 ± 0.001	0.925 ± 0.011	0.957 ± 0.087
	1:9	0.009 ± 0.002	0.022 ± 0.004	0.016 ± 0.001	0.943 ± 0.043	0.927 ± 0.063
DFV-loaded nanoparticle/ chitosan gel	1:1	0.009 ± 0.001	0.021 ± 0.002	0.010 ± 0.002	0.910 ± 0.014	0.962 ± 0.052
	1:3	0.010 ± 0.001	0.023 ± 0.003	0.012 ± 0.002	0.857 ± 0.021	0.916 ± 0.028
	1:9	0.012 ± 0.001	0.028 ± 0.004	0.016 ± 0.001	0.894 ± 0.042	0.882 ± 0.039

Abbreviations: DFV, diflucortolone valerate; SD, standard deviation.

Figure 6 Amount of DFV accumulated from formulations in the SC+epidermis (dark bars) and dermis (light bars) (n = 6).

Note: *Denotes significantly different from commercial cream and chitosan gel (P < 0.05).

Abbreviations: DFV, diflucortolone valerate; SC, stratum corneum.

Figure 7 Accumulation of DFV from nanoparticles in chitosan gels as a function of drug concentration in the SC+epidermis (dark bars) and dermis (light bars) (n = 6).

Abbreviations: DFV, diflucortolone valerate; SC, stratum corneum.

Figure 8 Changes in the paw thickness of the rats with respect to time after formulation application (n = 6).

Figure 9 Skin blanching profiles of formulations – the value of color difference (Δa) in rats versus time (n = 6).

Figure 10 Changes in TEWL values of the rats with respect to time after formulation application (n = 6).

Abbreviation: TEWL, transepidermal water loss.