Positively charged micelles based on a triblock copolymer demonstrate enhanced corneal penetration

Figures & data

Figure 1 Synthetic route of the copolymer.

Abbreviations: ε-CL, ε-caprolactone; PEI, polyethyleneimine; DCC, dicyclohexylcarbodiimide; NHS, N-hydroxy-succinimide; PEG-PCL-g-PEI, poly(ethylene glycol)-poly (ε-caprolactone)-g-polyethyleneimine.

Figure 2 ¹H NMR spectra of PEG-OH, PEG-PCL-OH, PEG-PCL-COOH in chloroform-d₁ and PEG-PCL-g-PEI in methanol-d₄ recorded on a Varian Unity 300 MHz spectrometer.

Abbreviations: NMR, nuclear magnetic resonance; PEG, poly(ethylene glycol); PCL, poly(ε-caprolactone); PEI, polyethyleneimine.

Figure 3 FTIR spectra of the diblock intermediates PEG-PCL-COOH (A) and PCI (B).

Abbreviations: PEG, poly(ethylene glycol); PCL, poly(ε-caprolactone); PCI, poly (ethylene glycol)-poly(ε-caprolactone)-g-polyethyleneimine; FTIR, Fourier transform infrared spectroscopy.

Table 1 Average particle sizes and zeta potentials of polymeric micelles and nanoparticles

	Size (nm)	Polydispersity	Zeta potentials (mV)
PCI micelle	27.74	0.212	+12.12
FDA nanoparticle	214.3	1.000	−0.80
FDA macroparticle	1,402	0.587	−1.11
PEG-PCL micelle	36.32	0.152	−0.24

Abbreviations: PEG, poly(ethylene glycol); PCL, poly(ε-caprolactone); PCI, poly(ethylene glycol)-poly(ε-caprolactone)-g-polyethyleneimine; FDA, fluorescein diacetate.

Figure 4 Schematic illustration of the formation of drug-loaded polymeric micelles.

Abbreviations: PEG, poly(ethylene glycol); PCL, poly(ε-caprolactone); PEI, polyethyleneimine.

Figure 5 The morphology and drug release behavior of micelles.

Notes: (A) Morphology of polymeric micelles determined by scanning electron microscopy (SEM). Scale bar represents 200 nm. (B) In vitro-release profile of CyA-loaded micelles at pH 7.2.

Abbreviations: CyA, cyclosporine; h, hours.

Table 2 Effect of initial drug content on its loading level in polymeric micelles, based on 10 mg of polymer in 10 mL solution

Initial drug content (mg)	Drug-loading content (%)	Drug-loading efficiency (%)
2	8.32	13.60
1	5.83	34.02
0.75	4.63	69.68
0.5	3.47	75.37
0.2	1.55	80.05
0.1	0.82	84.17

Figure 6 Representative in vivo two-photon microscopy images of corneal cross-sections at 15 min, 30 min, and 60 min after administration of different types of eye drops in C57BL/6 mice.

Notes: The administered eye drops were (A) FDA-loaded PCI micelles, (B) FDA nanoparticles, (C) FDA microparticles, and (D) FDA-loaded PEG-PCL micelles (magnification, 100×).

Abbreviations: min, minutes; FDA, fluorescein diacetate; PCI, poly(ethylene glycol)-poly(ε-caprolactone)-g-polyethyleneimine; PEG, poly(ethylene glycol); PCL, poly(ε-caprolactone).