Nerve terminals in the tumor microenvironment as targets for local infiltration analgesia.

Nerve terminals within the tumor microenvironment as potential pain-mitigating targets for local infiltration analgesia is relatively less explored. In this study, we examine the role of key analgesics administered as local infiltration analgesia in a model of cancer-induced bone pain (CIBP). CIBP was induced by administration of allogenic MRMT1 breast cancer cells in the proximal tibia of rats, and tumor mass characterized using radiogram, micro-CT, and histological analysis.

Secretome mediated interactions between sensory neurons and breast cancer cells.

The role of the nervous system in aiding cancer progression and metastasis is an important aspect of cancer pathogenesis. Interaction between cancer cells and neurons in an in vitro platform is a simple and robust method to further understand this phenomenon. In our study, we aimed to examine in vitro reciprocal effect between breast cancer cells and cancer-sensitized peripheral primary sensory neurons.

A Brief Review of In Vitro Models for Injury and Regeneration in the Peripheral Nervous System.

Nerve axonal injury and associated cellular mechanisms leading to peripheral nerve damage are important topics of research necessary for reducing disability and enhancing quality of life. Model systems that mimic the biological changes that occur during human nerve injury are crucial for the identification of cellular responses, screening of novel therapeutic molecules, and design of neural regeneration strategies. In addition to in vivo and mathematical models, in vitro axonal injury models provide a simple, robust, and reductionist platform to partially understand nerve injury pathogenesis and regeneration.

Effect of gold nanoparticle treated dorsal root ganglion cells on peripheral neurite differentiation.

The use of gold nanoparticles (AuNps) in applications connected to the peripheral nervous system (PNS) holds much promise in terms of therapeutic and diagnostic strategies. Despite their extensive use, a clear understanding of their effects on neurons and glia in the PNS is lacking. In this study, we set out to examine the effects of AuNps on dorsal root ganglion (DRG) cells, and how such AuNp-exposed cells could in-turn affect neurite differentiation.

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).

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--glycolic acid) microparticles (MPs). MPs of size 27.

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.

Effect of Peritumoral Bupivacaine on Primary and Distal Hyperalgesia in Cancer-Induced Bone Pain.

Background: Cancer-induced bone pain (CIBP) is a debilitating chronic pain condition caused by injury to bone nerve terminals due to primary or metastasized bone tumors. Pain manifests as enhanced sensitivity, not only over the affected bone site but also at distal areas that share common nerve innervation with the tumor. In this study, we aim to understand how tumor-induced primary and distal pain sensitivities are affected by bupivacaine-induced block of bone nerve endings in a rat model of CIBP.

Plumbagin induces paraptosis in cancer cells by disrupting the sulfhydryl homeostasis and proteasomal function.

Plumbagin (PLB) is an active secondary metabolite extracted from the roots of Plumbago rosea. In this study, we report that plumbagin effectively induces paraptosis by triggering extensive cytoplasmic vacuolation followed by cell death in triple negative breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa) and non-small lung cancer cells (A549) but not in normal lung fibroblast cells (WI-38). The vacuoles originated from the dilation of the endoplasmic reticulum (ER) and were found to be empty.

Hydrogel Scaffolds: Towards Restitution of Ischemic Stroke-Injured Brain.

Chronic brain injury following cerebral ischemia is a severe debilitating neurological condition, where clinical intervention is well known to decrease morbidity and mortality. Despite the development of several therapeutic strategies, clinical outcome in the majority of patients could be better improved, since many still face life-long neurological deficits. Among the several strategic options that are currently being pursued, tissue engineering provides much promise for neural tissue salvage and regeneration in brain ischemia.

Penetration of gold nanoparticles across the stratum corneum layer of thick-Skin.

Background: Transdermal particulate penetration across thick-skin, such as that of palms and sole, is particularly important for drug delivery for disorders such as small fiber neuropathies. Nanoparticle-based drug delivery across skin is believed to have much translational applications, but their penetration especially through thick-skin, is not clear.

Objective: This study specifically investigates the effectiveness of gold nanoparticles (AuNPs) for thick-skin penetration, especially across the stratum corneum (SC) as a function of particle size.

Neuroglia as targets for drug delivery systems: A review.

Targeted drug delivery within the nervous system is an emerging topic of research that involves designing and developing vehicular delivery systems that have the ability to target specific neuronal and non-neuronal cell types in the central and peripheral nervous system. Drugs, genetic material, or any other payloads can be loaded onto such delivery systems and could be used to treat, prevent or manage various neurological disorders. Currently, majority of studies in this field have been concentrated around targeted delivery to neurons.

Electrospun Polymeric Core-sheath Yarns as Drug Eluting Surgical Sutures.

Drug-coated sutures are widely used as delivery depots for antibiotics and anti-inflammatory drugs at surgical wound sites. Although drug-laden coating provides good localized drug concentration, variable loading efficiency and release kinetics limits its use. Alternatively, drug incorporation within suture matrices is hampered by the harsh fabrication conditions required for suture-strength enhancement.

Repeatable and adjustable on-demand sciatic nerve block with phototriggerable liposomes.

Pain management would be greatly enhanced by a formulation that would provide local anesthesia at the time desired by patients and with the desired intensity and duration. To this end, we have developed near-infrared (NIR) light-triggered liposomes to provide on-demand adjustable local anesthesia. The liposomes contained tetrodotoxin (TTX), which has ultrapotent local anesthetic properties.

Drug loaded bi-layered sponge for wound management in hyperfibrinolytic conditions.

Excessive bleeding due to premature clot lysis and secondary bacterial wound infection are two significant problems that contribute to increased morbidity in patients with hyperfibrinolytic conditions. In this study, we have developed a bi-layered sponge that promotes fibrin clot stability and prevents secondary bacterial wound infections. Using the technique of freeze-drying, a bi-layer matrix consisting of hyaluronic acid (HA) containing aminocaproic acid (amicar) and chitosan containing tetracycline loaded O-carboxymethyl chitosan nanoparticles (Tet-O-CMC NPs) were produced.

Forced Exercise Preconditioning Attenuates Experimental Autoimmune Neuritis by Altering Th1 Lymphocyte Composition and Egress.

A short-term exposure to moderately intense physical exercise affords a novel measure of protection against autoimmune-mediated peripheral nerve injury. Here, we investigated the mechanism by which forced exercise attenuates the development and progression of experimental autoimmune neuritis (EAN), an established animal model of Guillain-Barré syndrome. Adult male Lewis rats remained sedentary (control) or were preconditioned with forced exercise (1.

Multivesicular liposomal bupivacaine at the sciatic nerve.

Clinical translation of sustained release formulations for local anesthetics has been limited by adverse tissue reaction. Exparel™ (DepoFoam bupivacaine) is a new liposomal local anesthetic formulation whose biocompatibility near nerve tissue is not well characterized. Exparel™ injection caused sciatic nerve blockade in rats lasting 240 min compared to 120 min for 0.

Near-infrared-actuated devices for remotely controlled drug delivery.

A reservoir that could be remotely triggered to release a drug would enable the patient or physician to achieve on-demand, reproducible, repeated, and tunable dosing. Such a device would allow precise adjustment of dosage to desired effect, with a consequent minimization of toxicity, and could obviate repeated drug administrations or device implantations, enhancing patient compliance. It should exhibit low off-state leakage to minimize basal effects, and tunable on-state release profiles that could be adjusted from pulsatile to sustained in real time.

Biodegradable mesostructured polymer membranes.

The extracellular matrix (ECM) has a quasi-ordered reticular mesostructure with feature sizes on the order of tenths of to a few hundred nanometers. Approaches to preparing biodegradable synthetic scaffolds for engineered tissues that have the critical mesostructure to mimic ECM are few. Here we present a simple and general solvent evaporation-induced self-assembly (EISA) approach to preparing concentrically reticular mesostructured polyol-polyester membranes.

A Stiff Injectable Biodegradable Elastomer.

Injectable materials often have shortcomings in mechanical and drug-eluting properties that are attributable to their high water contents. A water-free, liquid four-armed PEG modified with dopamine end groups is described which changed from liquid to elastic solid by reaction with a small volume of Fe solution. The elastic modulus and degradation times increased with increasing Fe concentrations.

Topical drug formulations for prolonged corneal anesthesia.

Purpose: Ocular local anesthetics currently used in routine clinical practice for corneal anesthesia are short acting and their ability to delay corneal healing makes them unsuitable for long-term use. In this study, we examined the effect of the site 1 sodium channel blocker tetrodotoxin (TTX) on the duration of corneal anesthesia, applied with either proparacaine (PPC) or the chemical permeation enhancer octyl-trimethyl ammonium bromide (OTAB). The effect of test solutions on corneal healing was also studied.

Local toxicity from local anesthetic polymeric microparticles.

Background: Local tissue injury from sustained-release formulations for local anesthetics can be severe. There is considerable variability in reporting of that injury. We investigated the influence of the intrinsic myotoxicity of the encapsulated local anesthetic (lidocaine, low; bupivacaine, high) on tissue reaction in rats.

Prolonged nerve blockade delays the onset of neuropathic pain.

Aberrant neuronal activity in injured peripheral nerves is believed to be an important factor in the development of neuropathic pain. Pharmacological blockade of that activity has been shown to mitigate the onset of associated molecular events in the nervous system. However, results in preventing onset of pain behaviors by providing prolonged nerve blockade have been mixed.