Preparation of sustained release apremilast-loaded PLGA nanoparticles: in vitro characterization and in vivo pharmacokinetic study in rats

Figures & data

Table 1 Composition of APM-loaded PLGA NPs

NPs	PLGA (mg)	Drug (mg)	PVA (0.5% w/v)
F1	50	10	250
F2	100	10	250
F3	150	10	250

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles; PVA, polyvinyl alcohol.

Table 2 Particle characterization

Formulation code	Size (nm) ± SD	PDI	ZP (± mV)	%EE	%DL
F1	281.9±5.2	0.451±0.04	−32.8±1.6	39.5±1.1	1.3±0.1
F2	295.5±7.6	0.331±0.06	−39.1±2.8	46.7±1.5	1.5±0.3
F3	307.3±8.5	0.317±0.01	−43.4±2.6	61.1±1.9	1.9±0.1

Abbreviations: %DL, drug loading; %EE, entrapment efficiency; PDI, polydispersity index; ZP, zeta potential.

Figure 1 FTIR spectra of APM and APM-loaded PLGA NPs (F1–F3).

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nano-particles.

Figure 2 DSC thermogram of APM and APM-loaded PLGA NPs (F1–F3).

Abbreviations: APM, apremilast; DSC, differential scanning calorimetry; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.

Figure 3 Powder X-ray diffraction pattern of APM and APM-loaded PLGA NPs (F1–F3).

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.

Figure 4 SEM images of optimized APM-loaded PLGA NPs (F3).

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.

Figure 5 Release profile of pure APM and APM-loaded PLGA NPs (F3).

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nano-particles.

Figure 6 Higuchi release kinetics APM-loaded PLGA NPs (F3).

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.

Table 3 Pharmacokinetic profile of developed APM-loaded PLGA NPs

Parameters	Standard (mean ± SD)	F3 (mean ± SD)
Cmax (ng/mL)	132±34	164±16
Tmax (hours)	1	2
AUClast (ng hours/mL)	778±271	1,738±560a
AUCtot (ng hours/mL)	835±289	1,888±601a
Kel (hours)	0.12±0.03	0.06±0.007b
T1/2 (hours)	6.22±1.33	12.30±1.40c
MRT (hours)	8.52±1.31	16.30±2.38b
Relative bioavailability (%)	100	225%

Notes:

a P<0.05 significant compared with standard suspension.

b P<0.01 highly significant compared with normal suspension.

c P<0.001 extremely significant compared with normal suspension.

Abbreviations: APM, apremilast; MRT, mean residence time; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.

Figure 7 Pharmacokinetic profile of pure APM suspension and APM-loaded PLGA NPs (F3).

Abbreviations: APM, apremilast; PLGA NPs, poly(D,L-lactide-coglycolide) nanoparticles.

Figure 8 Representative MRM chromatogram of APM and IS in actual plasma sample at 1 hour after oral administration of APM (2 mg/kg).

Abbreviations: APM, apremilast; IS, internal standard; MRM, multiple reaction monitoring.