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. 2019 Dec;13(9):974-982.
doi: 10.1049/iet-nbt.2019.0002.

Poly(glycerol sebacate) nanoparticles for ocular delivery of sunitinib: physicochemical, cytotoxic and allergic studies

Sana Pirmardvand Chegini  1 , Jaleh Varshosaz  2 , Hamid Mirmohammad Sadeghi  3 , Alireza Dehghani  4 , Mohsen Minayian  5
Affiliations

Poly(glycerol sebacate) nanoparticles for ocular delivery of sunitinib: physicochemical, cytotoxic and allergic studies

Sana Pirmardvand Chegini et al. IET Nanobiotechnol. 2019 Dec.

Abstract

Poly(glycerol sebacate) (PGS) is a new biodegradable polymer with good biocompatibility used in many fields of biomedicine and drug delivery. Sunitinib-loaded PGS/gelatine nanoparticles were prepared by the de-solvation method for retinal delivery and treatment of diabetic retinopathy. The nanoparticles were characterised by Fourier-transform infrared and differential scanning calorimetry. The effects of different formulation variables including drug-to-carrier ratio, gelatine-to-PGS ratio, and glycerine-to-sebacate ratio were assessed on the encapsulation efficiency (EE%), particle size, release efficiency (RE), and zeta potential of the nanoparticles. The in vitro cytotoxicity of PGS/gelatine nanoparticles was studied on L929 cells. Draize test on rabbit eyes was also done to investigate the possible allergic reactions caused by the polymer. Glycerine/sebacic acid was the most effective parameter on the EE and RE. Gelatine-to-PGS ratio had the most considerable effect on the particle size while the RE was more affected by the glycerine/sebacic acid ratio. The optimised formulation (S1G0.7D21.2) exhibited a particle size of 282 nm, 34.6% EE, zeta potential of -8.9 mV, and RE% of about 27.3% for drug over 228 h. The 3-(4,5-dimethylthuazol-2-yl)-2,5-diphenyltetrazolium bromide assay indicated PGS/gelatine nanoparticles were not cytotoxic and sunitinib-loaded nanoparticles were not toxic at concentrations <36 nM.

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Figures

Fig. 1
Fig. 1
Schematic representation of the structure of glutaraldehyde cross‐linked PGS/gelatine nanoparticles loaded with sunitinib
Fig. 2
Fig. 2
FTIR spectrum of PGS, sunitinib‐loaded PGS/gelatine nanoparticles, drug‐free PGS/gelatine nanoparticles, gelatine, and sunitinib
Fig. 3
Fig. 3
Sunitinib release profiles from PGS/gelatine nanoparticles
Fig. 4
Fig. 4
Drug release profile from the optimised formulation of PGS/gelatine nanoparticles (S1 G0.7 D21.2)
Fig. 5
Fig. 5
FE‐SEM images of the optimised PGS/gelatin nanoparticles (S1 G0.7 D21.2)
Fig. 6
Fig. 6
DSC thermograms of free sunitinib, nanoparticles, drug‐loaded PGS/gelatine nanoparticles, physical mixture of sunitinib/PGS and PGS
Fig. 7
Fig. 7
Cell viability of blank nanoparticles and sunitinib‐loaded nanoparticles at various concentrations on L929 cells after (a) 24 h exposure, (b) 72 h exposure
Fig. 8
Fig. 8
Photographs of rabbits eyes during the experiment (a) Before distillation, (b) Just at distillation moment, (c) After 7 days, (d) After 21 days, (e) Left eye without treatment
See this image and copyright information in PMC

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