Ocular biocompatibility of dexamethasone acetate loaded poly(ɛ-caprolactone) nanofibers.

Electrospinning technique has been explored to produce nanofibers incorporated with drugs as alternative drug delivery systems for therapeutic purposes in various organs and tissues. Before such systems could potentially be used, their biocompatibility must be evaluated. In this study, dexamethasone acetate-loaded poly(ɛ-caprolactone) nanofibers (DX PCL nanofibers) were developed for targeted delivery in the vitreous cavity in the treatment of retinal diseases. Ocular biocompatibility was tested in vitro and in vivo. DX PCL nanofibers were characterized by scanning electron microscopy (SEM) and Fourier Transform InfraRed spectroscopy (FTIR) and the in vitro drug release from nanofibers was evaluated. The in vitro biocompatibility of DX PCL nanofibers was tested on both ARPE-19 and MIO-M1 cells using the cytotoxicity (MTT) test by morphological studies based on staining of the actin fibers in ARPE-19 cells and GFAP in MIO-M1 cells. The in vivo biocompatibility of DX PCL nanofibers was investigated after intravitreous injection in the rat eye, using spectral domain Optical Coherence Tomography (OCT) imaging of the retina. SEM results indicated that nanometric fibers were interconnected in a complex network, and that they were composed of polymer. FTIR showed that polymer and drug did not chemically interact after the application of the electrospinning technique. PCL nanofibers provided controlled DX release for 10 days. DX PCL nanofibers were not cytotoxic to the ocular cells, allowing for the preservation of actin fibers and GFAP in the cytoplasm of ARPE-19 and MIO-M1 cells, respectively, which are biomarkers of these ocular cell populations. DX PCL nanofibers did not affect the retinal and choroidal structures, and they did not induce abnormalities, hemorrhages, or retinal detachment, suggesting that the nanofibers were well tolerated. In eyes receiving DX PCL nanofibers, SD-OCT images were corroborated with histological analysis of neuroretina and choroid, which are ocular tissues that are extremely sensitive to toxic agents. Finally, the preservation of cone and rod photoreceptors indicated the light sensitivity of the animals. In conclusion, DX PCL nanofibers exhibited ocular biocompatibility and safety in the rodent eye and allow the release of dexamethasone. Further studies are required to appreciate the potential of these new drug delivery systems for the treatment of retinal diseases.

In vitro and in vivo ocular biocompatibility of electrospun poly(ɛ-caprolactone) nanofibers.

Biocompatibility is a requirement for the development of nanofibers for ophthalmic applications. In this study, nanofibers were elaborated using poly(ε-caprolactone) via electrospinning. The ocular biocompatibility of this material was investigated. MIO-M1 and ARPE-19 cell cultures were incubated with nanofibers and cellular responses were monitored by viability and morphology. The in vitro biocompatibility revealed that the nanofibers were not cytotoxic to the ocular cells. These cells exposed to the nanofibers proliferated and formed an organized monolayer. ARPE-19 and MIO-M1 cells were capable of expressing GFAP, respectively, demonstrating their functionality. Nanofibers were inserted into the vitreous cavity of the rat's eye for 10days and the in vivo biocompatibility was investigated using Optical Coherence Tomography (OCT), histology and measuring the expression of pro-inflammatory genes (IL-1ß, TNF-α, VEGF and iNOS) (real-time PCR). The OCT and the histological analyzes exhibited the preserved architecture of the tissues of the eye. The biomaterial did not elicit an inflammatory reaction and pro-inflammatory cytokines were not expressed by the retinal cells, and the other posterior tissues of the eye. Results from the biocompatibility studies indicated that the nanofibers exhibited a high degree of cellular biocompatibility and short-term intraocular tolerance, indicating that they might be applied as drug carrier for ophthalmic use.