Characterisation of 2-HP-β-cyclodextrin-PLGA nanoparticle complexes for potential use as ocular drug delivery vehicles

Figures & data

Figure 1. Size distribution and zeta-potential of PLGA nanoparticles and 2-HP-β-CD/PLGA nanoparticle complexes at a temperature of 25 ± 1 °C (n = 3). Particle size and zeta-potential of PLGA nanoparticles (A) and 2-HP-β-CD/PLGA nanoparticle complexes(B), respectively. PLGA, Polylactic-co-glycolic acid; 2-HP-β-CD, 2-HP-β-cyclodextrin.

Figure 2. TEM images of PLGA nanoparticles (A) and 2-HP-β-CD/PLGA nanoparticle complexes (B). (1: TEM ×5000; 2: TEM ×20000; 3: TEM ×50000; Bar = 200 nm). PLGA, Polylactic-co-glycolic acid; 2-HP-β-CD, 2-HP-β-cyclodextrin.

Figure 3. Infrared spectrogram of PLGA nanoparticles and 2-HP-β-CD/PLGA nanoparticle complexes (A: PLGA nanoparticles; B: 2-HP-β-CD/PLGA nanoparticle complexes).

Figure 4. DSC thermogram of PLGA nanoparticles and 2-HP-β-CD/PLGA nanoparticle complexes (A: Drug-loaded PLGA nanoparticles; B: Drug-loaded 2-HP-β-CD/PLGA nanoparticle complexes).

Figure 5. X-ray diffraction pattern of PLGA nanoparticles and 2-HP-β-CD/PLGA nanoparticle complexes (A: Drug-loaded PLGA nanoparticles; B: Drug-loaded 2-HP-β-CD/PLGA nanoparticle complexes).

Figure 6. The results of in vitro release in PBS (A), STF(B), and SAF(C) at a temperature of 34 ± 0.5 °C (mean ± SD, n = 3).

Figure 7. Cumulative permeation (excised rabbit corneas) at a temperature of 34 ± 1 °C (mean ± SD, n = 3) Polylactic-co-glycolic acid; 2-HP-β-CD, 2-HP-β-cyclodextrin.

Table 1. P_app and $J_{\mathrm{ss}}\mathrm{ }$ of nanoparticles in the cornea in vitro mean ± S.D (n = 3).

	Papp$(\times {10}^{-7}\mathrm{c}\mathrm{m}·{\mathrm{s}}^{-1})$	$J_{\mathrm{ss}}(\times {10}^{-3}\mathrm{\mu }\mathrm{g}·{\mathrm{s}}^{-1}·{\mathrm{cm}}^{-2})$
TA aqueous suspension	8.69	0.17
PLGA nanoparticles	9.83	0.20
2-HP-β-CD/PLGA nanoparticle complexes	66.36	1.33

$P_{\text{app}}:$ the apparent permeability coefficient; J_ss: the steady-state flow rate.

Table 2. Release model of triamcinolone acetonide in the cornea in vitro.

Sample	Release model	Equation	$R^2$
TA aqueous suspension	Zero-order	Q = 0.3146t − 0.1793	0.9963
PLGA nanoparticles	Ritger-Peppas	lnQ = 1.5036lnt − 2.5959	0.9409
2-HP-β-CD/PLGA nanoparticle complexes	First-order	ln(100 − Q)= −0.0282t + 4.6186	0.9997

Table 3. Result of eye irritation.

Location	Normal saline		TA aqueous suspension		PLGA NPs		2-HP-β-CD/PLGA NP complexes
	Single	Long-term	Single	Long-term	Single	Long-term	Single	Long-term
Cornea	0	0	0	0	0	0	0	0
Iris	0	0	0	0	0	0	0	0
Conjunctival congestion	0	0	0	0	0	0.5	0	0.3
Conjunctival oedema	0	0.4	0	0.6	0	0	0	0
Secretions	0	0	0	0	0	0	0	0
Total score	0	0.4	0	0.6	0	0.5	0	0.3

Figure 8. Histopathology images of the cornea (1), iris (2), and sclera (3) after treatment with: Normal saline(A), PLGA nanoparticles (B), and 2-HP-β-CD/PLGA nanoparticle complexes (C). PLGA, Polylactic-co-glycolic acid; 2-HP-β-CD, 2-HP-β-cyclodextrin.

Figure 9. Concentration–time curves of TA in the aqueous humor (mean ± SD, n = 6). PLGA, Polylactic-co-glycolic acid; 2-HP-β-CD, 2-HP-β-cyclodextrin.

Table 4. Pharmacokinetic parameters of TA in the aqueous humour after topical instillation (n = 3).

Formulation	Cmax	AUC0→t	MRT	Tmax	VRT
	mg·L^−1	h*h*mg·L^−1	h	h	h^2
2-HP-β-CD-NPs	13.25 ± 2.87	24.531 ± 1.64	2.299 ± 0.18	1.5 ± 0	1.55 ± 0.44
NPs	0.57 ± 0.28	1.199 ± 0.35	2.286 ± 0.23	1.5 ± 0	1.363 ± 0.18
Aqueous solution	0.36 ± 0.17	0.546 ± 0.17	1.982 ± 0.15	1.5 ± 0	0.658 ± 0.12

C_max: peak concentration; AUC_0→t: area under the curve; MRT: mean residence time; T_max: the peak time; VRT: variance of residence time.