Neuronal delivery of nanoparticles via nerve fibres in the skin.

Accessing the peripheral nervous system (PNS) by topically applied nanoparticles is a simple and novel approach with clinical applications in several PNS disorders. Skin is richly innervated by long peripheral axons that arise from cell bodies located distally within ganglia. In this study we attempt to target dorsal root ganglia (DRG) neurons, via their axons by topical application of lectin-functionalized gold nanoparticles (IB4-AuNP). In vitro, 140.2 ± 1.9 nm IB4-AuNP were found to bind both axons and cell bodies of DRG neurons, and AuNP applied at the axonal terminals were found to translocate to the cell bodies. Topical application of IB4-AuNP on rat hind-paw resulted in accumulation of three to fourfold higher AuNP in lumbar DRG than in contralateral control DRGs. Results from this study clearly suggest that topically applied nanoparticles with neurotropic targeting ligands can be utilized for delivering nanoparticles to neuronal cell bodies via axonal transport mechanisms.

Anisotropic microparticles for differential drug release in nerve block anesthesia.

Microparticle shape, as a tunable design parameter, holds much promise for controlling drug-release kinetics from polymeric microparticulate systems. In this study we hypothesized that the intensity and duration of a local nerve block can be controlled by administration of bupivacaine-loaded stretch-induced anisotropic poly(lactic-co-glycolic acid) microparticles (MPs). MPs of size 27.3 ± 8.5 µm were synthesized by single emulsion method and subjected to controlled stretching force. The aspect ratio of the anisotropic-bupivacaine MPs was quantified, and bupivacaine release was measured in vitro. The anisotropic MPs were administered as local nerve block injections in rats, and the intensity and duration of local anesthesia was measured. Bupivacaine-loaded anisotropic MPs used in this study were ellipsoid in shape and exhibited increased surface pores in comparison to spherical MPs. Anisotropic MPs exhibited a higher rate of bupivacaine release in vitro, and showed significantly (P < 0.05) stronger sensory nerve blocking as compared to spherical bupivacaine MPs, even though the duration of the nerve block remained similar. This study demonstrates the utility of stretch-induced anisotropic MPs in controlling drug release profiles from polymeric MPs, under both in vitro and in vivo conditions. We show that shape, as a tunable design parameter, could play an important role in engineering drug-delivery systems.

Electrical stimulation of co-woven nerve conduit for peripheral neurite differentiation.

Electrically stimulable nerve conduits are implants that could potentially be utilized in patients with nerve injury for restoring function and limb mobility. Such conduits need to be developed from specialized scaffolds that are both electrically conductive and allow neuronal attachment and differentiation. In this study, we investigate neural cell attachment and axonal differentiation on scaffolds co-woven with poly-(L-lactic acid) (PLLA) yarns and conducting threads. Yarns obtained from electrospun PLLA were co-woven with polypyrrole (PPy)-coated PLLA yarns or ultrathin wires of copper or platinum using a custom built low-resistance semi-automated weaving machine. The conducting threads were first electrically characterized and tested for stability in cell growth media. Suitability of the conducting threads was further assessed via cell viability studies using PC12 cells. Neurite growth was then quantified after electrically stimulating rat dorsal root ganglion (DRG) sensory neurons cultured on the woven scaffolds. Electrical conductivity tests and cellular viability studies demonstrated better bio-tolerability of platinum wires over PPy-coated PLLA yarns and copper wires. Electrically stimulated DRG neurons cultured on platinum-PLLA co-woven scaffolds showed enhanced neurite outgrowth and length. We demonstrate that a woven scaffold design could be utilized to incorporate conducting materials into cell-tolerable polymer yarns for developing electrically stimulable nerve conduits.