Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice

Abstract

Background: Neural interfaces often elicit inflammatory responses and neuronal loss in the surrounding tissue which adversely affect the function and longevity of the implanted device. Minocycline, an anti-inflammatory pharmaceutics with neuroprotective properties, may be used for reducing the acute brain tissue responses after implantation. However, conventional administration routes require high doses which can cause adverse systemic side effects. Therefore, the aim of this study was to develop and evaluate a new drug-delivery-system for local and sustained administration of minocycline in the brain. Methods: Stainless steel needles insulated with Parylene-C were dip-coated with non-crosslinked gelatin and minocycline-loaded PLGA nanoparticles (MC-NPs) were incorporated into the gelatin-coatings by an absorption method and subsequently trapped by drying the gelatin. Parylene-C insulated needles coated only with gelatin were used as controls. The expression of markers for activated microglia (CD68), all microglia (CX3CR1-GFP), reactive astrocytes (GFAP), neurons (NeuN) and all cell nuclei (DAPI) surrounding the implantation sites were quantified at 3 and 7 days after implantation in mice. Results: MC-NPs were successfully incorporated into gelatin-coatings of neural implants by an absorption method suitable for thermosensitive drug-loads. Immunohistochemical analysis of the in vivo brain tissue responses, showed that MC-NPs significantly attenuate the activation of microglial cells without effecting the overall population of microglial cells around the implantation sites. A delayed but significant reduction of the astrocytic response was also found in comparison to control implants. No effect on neurons or total cell count was found which may suggest that the MC-NPs are non-toxic to the central nervous system. Conclusions: A novel drug-nanoparticle-delivery-system was developed for neural interfaces and thermosensitive drug-loads. The local delivery of MC-NPs was shown to attenuate the acute brain tissue responses nearby an implant and therefore may be useful for improving biocompatibility of implanted neuro-electronic interfaces. The developed

Osteogenic differentiation system based on biopolymer nanoparticles for stem cells in simulated microgravity

“…At the same time, the high cost and inactivation of BMPs limit their extensive use in bone repair. It has been reported that nanoparticles (NPs) produced from poly (lactic acid-co-glycolic acid) (PLGA) [10][11][12], poly (L-lactic acid) (PLA) [13][14][15] and polycaprolactone (PCL) [16][17][18] can release recombinant human BMP2 or BMP7. Nevertheless, these BMPs only increased alkaline phosphatase (ALP) activity for a short time.…”

Bacteria Invade the Brain Following Sterile Intracortical Microelectrode Implantation

“…Antibiotics are commonly used as part of post-surgery treatments and have been investigated acutely in mice, showing a bene cial reduction of glial encapsulation post-implantation of MEAs [51][52][53] . However, it is unlikely that regular antibiotic treatment throughout the duration of microelectrode implantation would represent a practical clinical solution to improved microelectrode performance.…”

Commonly Overlooked Factors in Biocompatibility Studies of Neural Implants

“…[102] Mechanical sensitivity by neurons has also been demonstrated, however, the exact implications are unknown. [27,157] The soma can withstand some compressive disturbance [42,43,123,158] as evidenced by histological examination, however, reports indicate that mechanical disruption can significantly alter neuronal spike dynamics. [157,159] As early as 1970, Humphrey suggested that improved neural SU recording performance using individually advanceable microelectrode arrays could be achieved when insertion-induced tissue compression was allowed to resolve before final electrode positioning.…”