Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

Figures & data

Figure 1 Barriers and strategy of administration for delivering different types of formulations to the inner eye.

Figure 2 Schematic illustration of differently charged L/NP carriers containing dexamethasone.

Abbreviation: L/NP, lipid nanoparticle.

Figure 3 Formative variables of dexamethasone-loaded L/NP carriers.

Abbreviations: L/NP, lipid nanoparticle; PDI, polydispersity index.

Table 1 Formative variables of complex solubilizer L/NPs (mean ± SD, n=3)

Formulative variables	Particle size distribution (nm)	Polydispersity	Loading efficiency (%)	Loading capacity (%)
Acetone/ethanol	118.7±42.4	0.136±0.032	70.3±5.8	3.1±0.1
Dichloromethane/ethanol	232.6±94.6	0.118±0.033	45.2±8.6	1.7±0.1
Trichloromethane/acetone	762.3±194.2	0.285±0.016	31.8±1.2	0.8±0.2

Abbreviation: L/NPs, lipid nanoparticles.

Table 2 Formative variables of L/NPs (mean ± SD, n=3)

Preparation	Mean particle size	Size distribution	Polydispersity	Zeta potential
(+) L/NPs	155.03±1.47 nm	118.2±87.5 nm	0.109±0.003	+29.99±4.63 mV
(−) L/NPs	132.25±0.07 nm	180.1±74.5 nm	0.130±0.008	−25.73±0.78 mV

Abbreviation: L/NPs, lipid nanoparticles.

Figure 4 Image of L/NP size distribution and zeta potential.

Notes: (A1/B1) (+) L/NPs; (A2/B2) (−) L/NPs: 1, distribution of particle size; 2, zeta potential.

Abbreviation: L/NPs, lipid nanoparticles.

Figure 5 Transmission electron microscopic morphology of the L/NPs.

Notes: (A) (+) L/NPs; (B) (−) L/NPs.

Abbreviation: L/NPs, lipid nanoparticles.

Table 3 Transcorneal permeation parameters of different formulations (mean ± SD, n=3)

Formulations	Papp (cm·h−^Citation1)	Jss (μg·h^−1·cm^−2)	EP*	Hydration level
Aqueous solution	0.0959±0.03	8.893	1	85.0%±2.39%
(+) L/NPs	0.2592±0.08	24.0306	2.7	79.5%±0.97%
(−) L/NPs	0.1763±0.05	16.3407	1.8	78.2%±1.26%

Notes:

* EP = P_app ([+] NPs)/P_app (solution); EP = P_app ([−] NPs)/P_app (solution).

Abbreviations: EP, enhanced penetration; L/NPs, lipid nanoparticles.

Table 4 In vitro drug release fitting equation of different formulations

Fitting equation	Parameter	First-order equation	Higuchi equation	Niebergull equation	Hixson–Crowell equation	Ritger–Peppas equation	Weibull equation
Aqueous solution	R^2	0.924	0.965	0.918	0.92	0.969	0.971
	AIC	−17.938	−20.019	–	–	−6.234	−6.204
(+) L/NPs	R^2	0.892	0.901	0.871	0.878	0.921	0.929
	AIC	−7.317	−9.717	−12.102	−14.181	−1.985	−1.516
(−) L/NPs	R^2	0.919	0.884	0.890	0.8968	0.904	0.912
	AIC	−8.468	−9.529	−6.203	−8.283	−0.0374	−0.019

Abbreviations: AIC, Akaike information criterion; L/NPs, lipid nanoparticles.

Figure 6 Histopathology microscopy of the cornea (1), iris (2), sclera (3) after treatment with different formulations for 7 days.

Notes: (A) Control; (B) (+) L/NPs; (C) (−) L/NPs, n=6.

Abbreviation: L/NPs, lipid nanoparticles.

Table 5 Pharmacokinetic parameters of dexamethasone in aqueous humor (mean ± SD, n=6)

Key parameters	Aqueous solution	(+) L/NPs	(−) L/NPs
Volume of instillation	1 mL	1 mL	1 mL
Tmax(h)	0.5	6	5
Cmax(μg/L)	14.601±0.309	34.578±0.333	17.126±0.472
AUC0–t(μg/L/h)	39.410±3.779	185.139±2.185	83.353±0.773
MRT (h)	2.434±0.112	5.192±0.329	4.622±0.014

Abbreviations: AUC, area under the curve; L/NPs, lipid nanoparticles; MRT, mean retention time.

Figure 7 Concentration of dexamethasone in rabbit aqueous humor as a function of time after instillation of the aqueous solution and L/NPs (n=6, mean ± SD).

Abbreviation: L/NPs, lipid nanoparticles.

LoftssonaTJarvinenTCyclodextrins in ophthalmic drug deliveryAdv Drug Deliv Rev1999361597910837709

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