Deformable Liposomal Hydrogel for Dermal and Transdermal Delivery of Meloxicam

Figures & data

Figure 1 Flow diagram of liposomal hydrogel formulation preparation.

Table 1 The Composition and Type of the Vesicles Investigated in the Study

Formulation ID	Description	PC^a (3.2% w/v)	MX^b (0.32% w/v)	Chol^c (0.16% w/v)	CPC^d (0.96% w/v)	QCT^e (0.24% w/v)	DHQ^f (0.8% w/v)
CLP	Conventional Liposome	✔	✔	✔
TFS	Transfersome	✔	✔	✔	✔
FLSQ	Flavosome Q	✔	✔	✔	✔	✔
FLSD	Flavosome D	✔	✔	✔	✔		✔

Note: ^aPhosphatidylcholine, ^bMeloxicam, ^cCholesterol, ^dCetylpyridinium chloride, ^eQuercetin, ^fDihydroquercetin.

Table 2 Physiochemical Properties of the Obtained Vesicles. Data are Presented as Means±SD (n=3)

Sample ID	Description	MX^a				Average Diameter (nm)	PDI^d	Zeta Potential (mV)
		%EE^b		%DL^c	Content (mg/mL)
CLP	Conventional Liposome	9.13±1.13		0.91±0.11	0.292±0.036	111.4±0.2	0.257±0.008	2.1±0.3
TFS	Transfersome	96.04±1.98		9.61±0.20	3.075±0.063	62.3±0.3	0.287±0.013	32.2±0.6
FLSQ	Flavosome-Q	94.39±1.57		9.44±0.16	3.022±0.050	66.0±0.6	0.281±0.002	27.8±0.5
FLSD	Flavosome-D	92.24±0.36		9.23±0.04	2.954±0.011	97.0±1.3	0.298±0.023	23.6±0.7

Note: ^aMeloxicam, ^b% Entrapment Efficiency, ^c%Drug Loading, ^dPolydispersity Index.

Table 3 Deformability Index of Liposomal Vesicles. Data are Presented as Means±SD (n=3)

Formulation	Particles Size Before Extrusion (nm)	Particles Size After Extrusion (nm)	Deformability Index
CLP	105.2±0.7	59.0±0.4	0.561±0.004
TFS	80.8±0.6	67.6±1.0	0.837±0.012*
FLSQ	82.4±0.7	79.8±0.7	0.969±0.008*
FLSD	96.1±1.4	95.8±0.1	0.997±0.001*

Note: *P<0.05 vs CLP.

Figure 2 Transmission electron microscopy images of (A) conventional liposomes; (B) transfersomes; (C) flavosomes-Q; (D) flavosomes-D.

Figure 3 Amplitude sweeping plots obtained for the gels (A) and calculated cross-over values (B) (n=3 for each formulation, data are presented as means±SD).

Figure 4 Temperature sweeping of the gels (n=3 for each formulation, data are presented as means±SD).

Figure 5 Transmission electron microscopy images of (A) MX-gel, (B) CLP-gel, (C) TFS-gel, (D) FLSQ-gel, (E) FLSD-gel.

Table 4 Physical Properties of the Obtained LiposomalVesicles and Liposomal Gel Formulations. Data are Presented as Means±SD (n=3)

Sample ID	Description	Liposomal Vesicles		Liposomal Gel
		Average Diameter (nm)	PDI^a	Average Diameter (nm)	PDI
CLP	Conventional Liposome	111.4±0.2	0.257±0.008	245.4±3.4	0.133±0.012
TFS	Transfersome	62.3±0.3	0.287±0.013	231.0±1.2	0.147±0.015
FLSQ	Flavosome-Q	66.0±0.6	0.281±0.002	236.2±1.8	0.187±0.015
FLSD	Flavosome-D	97.0±1.3	0.298±0.023	246.8±5.2	0.178±0.023

Note: ^aPolydispersity Index.

Table 5 Permeation Parameter Obtained for the Investigated Gel Formulations. Data are Presented as Means±SD (n=3 for Each Formulation)

Formulation	Jss^a (μg/cm^2/h)	Concentration (μg/mg)^c	Kp^b (mg/cm^2/h)	Enhancement Ratio	Lag Time (h)
CLP-gel	–	0.219±0.005	–	–	–
MX-gel	0.017±0.006	0.428±0.057	(3.93±1.47)x10^−2	1	4.17±1.34
TFS-gel	0.128±0.010*	1.906±0.014	(6.71±0.52)x10^−2*	1.71	4.42±0.60
FLSQ-gel	0.222±0.014*^#	1.885±0.030	(11.78±0.76)x10^−2*^#	3.00	2.54±0.77^#
FLSD-gel	0.245±0.010*^#	2.064±0.042	(11.89±0.50)x10^−2*^#	3.03	2.89±0.55^#

Note: *P<0.05 vs MX-gel, ^#P<0.05 vs TFS-gel, ^aJ_ss: steady-state flux, ^bK_p: permeability coefficient, ^cConcentration is expressed as μg of meloxicam/mg of gel formulation.

Figure 6 (A) Ex vivo drug permeation profiles of meloxicam (MX)-loaded liposomal gel formulations over 24 hours; (B) MX deposited in the different layers of skin after 24-hour skin permeation study from formulations tested (n= for each formulation, data are presented as means±SD).

Table 6 Kinetic Models for the Investigated Gel Formulations

Formulation	Zero Order		First Order		Higuchi Model
	K^a	r^2 b	K	r^2	K	r^2
MX-Gel	0.008	0.969	0.04	0.873	0.053	0.919
TFS-Gel	0.064	0.936	0.074	0.873	0.399	0.861
FLSQ-Gel	0.111	0.955	0.059	0.924	0.701	0.898
FLSD-Gel	0.123	0.947	0.067	0.867	0.774	0.889

Note: ^aK: slope, ^br²: correlation coefficient.

Figure 7 Confocal laser scanning microscopy images taken at different depths of the full thickness human cadaver skin after 24 hours permeation of Dil-labeled gel formulations containing (A) untreated skin, (B) CLP-gel, (C) TFS-gel, (D) FLSQ-gel, and (E) FLSD-gel (magnification 10X).

Figure 8 Stability study results of (A) meloxicam-loaded liposomal suspensions at 5±3°C for 30, 60, and 90 days, and (B) meloxicam-loaded liposomal gel formulations at 25±5°C for 30, 60, and 90 days (n=3 for each formulation).