PLGA Nanoparticle Platform for Trans-Ocular Barrier to Enhance Drug Delivery: A Comparative Study Based on the Application of Oligosaccharides in the Outer Membrane of Carriers

Figures & data

Figure 1 The effects of PLGA MWs on the NPs (LA/GA 50:50) particle size and in vitro drug release.

Notes: Data are expressed as mean ± standard deviation (n = 6). *P < 0.05, compared to the corresponding parameters of PLGA NPs (MW 10 kDa).

Abbreviations: NPs, nanoparticles; LA/GA, lactide/glycolide; MW, molecular weight; D90, cumulative particle size distribution of 90% NPs.

Figure 2 The effects of PLGA LA/GA ratios on in vitro drug release and corneal permeability of the NPs (MW 10,000).

Notes: Data are expressed as mean ± standard deviation (n = 6). *P < 0.05, compared to the corresponding parameters of PLGA NPs (LA/GA ratio 50/50).

Abbreviations: NPs, nanoparticles; LA/GA, lactide/glycolide; MW, molecular weight.

Figure 3 Differential scanning calorimetry thermograms of (A) PLGA NPs, (B) 2-HP-β-CD/PLGA NPs, (C) trehalose/PLGA NPs and (D) chitosan oligosaccharide/PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Figure 4 X-ray diffraction patterns of (A) PLGA NPs, (B) 2-HP-β-CD/PLGA NPs, (C) trehalose/PLGA NPs, and (D) chitosan oligosaccharide/PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Figure 5 Infrared spectrograms of (A) PLGA NPs, (B) 2-HP-β-CD/PLGA NPs, (C) trehalose/PLGA NPs, and (D) chitosan oligosaccharide/PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Figure 6 Particle size distribution and zeta potential of (A) PLGA NPs, (B) 2-HP-β-CD/PLGA NPs, (C) trehalose/PLGA NPs, (D) chitosan oligosaccharide/PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Figure 7 TEM images of (A) PLGA NPs, (B) 2-HP-β-CD/PLGA NPs, (C) trehalose/PLGA NPs, and (D) chitosan oligosaccharide/PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; TEM, transmission electron microscopy.

Figure 8 (A) The cumulative percentage of triamcinolone acetonide released in artificial tear fluid. (B) Permeability of triamcinolone acetonide across excised rabbit corneas (■: PLGA NPs; ▼: 2-HP-β-CD/PLGA NPs; ▲: trehalose/PLGA NPs; ●: chitosan oligosaccharide/PLGA NPs).

Note: Points are mean ± standard deviation (n = 6).

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Table 1 Release Models of Triamcinolone Acetonide from Determination Preparations Across Corneas in vitro

Preparations	Release Models	Fitting Equations	R^2
PLGA NPs	Zero order	Q = 0.5323t-0.7535	0.8998
	First order kinetics	ln (100-Q) = −0.0054t+4.6129	0.8979
	Higuchi	Q = 1.9491-2.2962	0.8139
	Ritger-Peppas	lnQ = 1.3951lnt-1.8262	0.9172
2-HP-β-CD/PLGA NPs	Zero order	Q = 5.1285t-2.0759	0.9988
	First order kinetics	ln (100-Q) = −0.0655t+4.6498	0.9990
	Higuchi	Q = 19.654-18.633	0.9894
	Ritger-Peppas	lnQ = 1.2684lnt+1.1008	0.9361
Trehalose/PLGA NPs	Zero order	Q = 0.6662t-0.9301	0.9721
	First order kinetics	ln (100-Q) = −0.0068t+4.6148	0.9706
	Higuchi	Q = 2.4882-2.9552	0.9147
	Ritger-Peppas	lnQ = 1.8977lnt-2.3834	0.9967
Chitosan oligosaccharide/PLGA NPs	Zero order	Q = 1.3538t-1.7899	0.9855
	First order kinetics	ln (100-Q) = −0.0142t+4.6244	0.9831
	Higuchi	Q = 5.088-5.9667	0.9392
	Ritger-Peppas	lnQ = 2.1694lnt-2.0672	0.9857

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Table 2 Permeation Parameters of the Different Preparations Through the Excised Corneas

Preparation	(cm·s^−1)	(μg·s^−1·cm^−2)
PLGA NPs	10.72 ± 3.80	0.21 ± 0.08
2-HP-β-CD/PLGA NPs	53.70 ± 4.73**	1.00 ± 0.11**
Trehalose/PLGA NPs	14.72 ± 2.86*	0.28 ± 0.08*
Chitosan oligosaccharide/PLGA NPs	16.06 ± 3.15*	0.31 ± 0.06*

Notes: Data are expressed as mean ± standard deviations (n = 6). *P < 0.05, **P < 0.01, compared to the corresponding parameters of PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; , apparent permeability coefficient; , steady flow.

Table 3 Pharmacokinetics Parameters of Triamcinolone Acetonide in Aqueous Humor After Topical Instillation

Formulations	Cmax	AUC0→t	MRT	Tmax	VRT
	mg·L^−1	h·h·mg·L^−1	h	h	h^2
PLGA NPs	0.60 ± 0.14	0.82 ± 0.22	1.71 ± 0.12	1.5 ± 0	0.63 ± 0.21
2-HP-β-CD/PLGA NPs	11.51 ± 1.26**	21.29 ± 1.64**	1.93 ± 0.15*	1.5 ± 0	0.75 ± 0.36
Trehalose/PLGA NPs	1.11 ± 0.52*	1.25 ± 0.55*	1.78 ± 0.07	1.5 ± 0	0.85 ± 0.15
Chitosan oligosaccharide/PLGA NPs	0.62 ± 0.26	0.84 ±0.43	1.69 ± 0.10	1.5 ± 0	0.71 ± 0.10

Notes: Data are expressed as mean ± standard deviations (n = 6). *P < 0.05, **P < 0.01, compared to the corresponding parameters of PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin; C_max, peak concentrations; AUC_0→t, area under curve; MRT, mean residence time; T_max, time to reach maximum concentration; VRT, variance of residence time.

Figure 9 Pharmacokinetic profiles of the NPs in aqueous humor. (■: PLGA NPs; ▼: 2-HP-β-CD/PLGA NPs; ▲: trehalose/PLGA NPs; ●: chitosan oligosaccharide/PLGA NPs).

Note: Points are mean ± standard deviation (n = 6).

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.

Figure 10 Histopathological images of rabbit corneas treated with (A) PLGA NPs, (B) 2-HP-β-CD/PLGA NPs, (C) trehalose/PLGA NPs, and (D) chitosan oligosaccharide/PLGA NPs.

Abbreviations: NPs, nanoparticles; 2-HP-β-CD, 2-hydroxypropyl-β-cyclodextrin.