Quantification of tissue reaction.

(A) Inflammation and (B) myotoxicity scores of animals injected at the sciatic nerve with benzonatate and bupivacaine. Equieffective concentrations have the same shading. Data are medians with 25th and 75th percentiles, n = 4 for all groups. * p < 0.05 for the comparison of equieffective concentrations by Mann-Whitney U test.</p

Formulations injected at the sciatic nerve.

IntroductionBenzonatate is an FDA-approved antitussive agent that resembles tetracaine, procaine, and cocaine in its chemical structure. Based on structural similarities to known local anesthetics and recent findings of benzonatate exerting local anesthetic-like effects on voltage-gated sodium channels in vitro, we hypothesized that benzonatate will act as a local anesthetic to yield peripheral nerve blockade.MethodsBenzonatate was injected at the sciatic nerve of Sprague-Dawley rats. Sensory and motor blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Additionally, the effect of co-injection with tetrodotoxin and Tween 80 (a chemical permeation enhancer) was examined. Myotoxicity of benzonatate was assessed in vivo by histological analysis.ResultsBenzonatate produced a concentration-dependent sensory and motor nerve blockade with no appreciable systemic effects. Co-injection with tetrodotoxin or Tween 80 produced prolongation of sensory nerve blockade. Histologic assessment showed significant inflammation and myotoxicity from benzonatate injection, even at low concentrations.ConclusionThis study demonstrates that benzonatate does act as a local anesthetic at the peripheral nerve, with sensory and motor nerve blockade. Benzonatate interacts with tetrodotoxin and Tween 80 to prolong nerve blockade. However, benzonatate causes significant myotoxicity, even at subtherapeutic concentrations.</div

Tissue toxicity of benzonatate: Inflammation and myotoxicity scores.

Tissue toxicity of benzonatate: Inflammation and myotoxicity scores.</p

Quantification of tissue reaction represented by a box and whisker plot.

(a) Inflammation and (b) myotoxicity scores of animals injected at the sciatic nerve with benzonatate and bupivacaine. Equieffective concentrations have the same shading. Data are medians with 25th and 75th percentiles, n = 4 for all groups. Note that the median value (bar) overlaps with the 25th or 75th percentiles (box) for multiple data points. * P (DOCX)</p

Formulations injected at the sciatic nerve.

IntroductionBenzonatate is an FDA-approved antitussive agent that resembles tetracaine, procaine, and cocaine in its chemical structure. Based on structural similarities to known local anesthetics and recent findings of benzonatate exerting local anesthetic-like effects on voltage-gated sodium channels in vitro, we hypothesized that benzonatate will act as a local anesthetic to yield peripheral nerve blockade.MethodsBenzonatate was injected at the sciatic nerve of Sprague-Dawley rats. Sensory and motor blockade were assessed using a modified hot plate test and a weight-bearing test, respectively. Additionally, the effect of co-injection with tetrodotoxin and Tween 80 (a chemical permeation enhancer) was examined. Myotoxicity of benzonatate was assessed in vivo by histological analysis.ResultsBenzonatate produced a concentration-dependent sensory and motor nerve blockade with no appreciable systemic effects. Co-injection with tetrodotoxin or Tween 80 produced prolongation of sensory nerve blockade. Histologic assessment showed significant inflammation and myotoxicity from benzonatate injection, even at low concentrations.ConclusionThis study demonstrates that benzonatate does act as a local anesthetic at the peripheral nerve, with sensory and motor nerve blockade. Benzonatate interacts with tetrodotoxin and Tween 80 to prolong nerve blockade. However, benzonatate causes significant myotoxicity, even at subtherapeutic concentrations.</div

Representative light microscopy of hematoxylin/eosin-stained sections of nerves (n), muscles (m), and surrounding tissues at the site of injection.

Tissues were collected 4 days after injection with equieffective concentrations of benzonatate and bupivacaine. Infl: Inflammation. Mtox: Myotoxicity. Nec: Necrosis.</p

Characterization of benzonatate.

(A) chemical structure of benzonatate (B) LC-MS of benzonatate used in this study.</p

Effect of co-administration of benzonatate (Benz, 12.4 mM) with TTX (30 μM) or T80 (23 mM).

(A) frequency of successful sensory nerve block (B) duration of sciatic sensory and motor nerve block. Data are medians with 25th and 75th percentiles, n = 8 per group except benzonatate administration with n = 12 (note that administration of T80 alone resulted in no sensory or motor block for all animals). Duration of nerve block were compared by a Kruskal-Wallis test (p = 0.0001) with post-hoc pairwise comparison with Bonferroni correction (p<0.01 for sensory and motor blockade following co-administration of benzonatate and TTX compared to benzonatate alone).</p

Delivery of Liposomal Quantum Dots <i>via</i> Monocytes for Imaging of Inflamed Tissue

Quantum dots (QDs), semiconductor nanocrystals, are fluorescent nanoparticles of growing interest as an imaging tool of a diseased tissue. However, a major concern is their biocompatibility, cytotoxicity, and fluorescence instability in biological milieu, impeding their use in biomedical applications, in general, and for inflammation imaging, in particular. In addition, for an efficient fluorescent signal at the desired tissue, and avoiding systemic biodistribution and possible toxicity, targeting is desired. We hypothesized that phagocytic cells of the innate immunity system (mainly circulating monocytes) can be exploited as transporters of specially designed liposomes containing QDs to the inflamed tissue. We developed a liposomal delivery system of QDs (LipQDs) characterized with high encapsulation yield, enhanced optical properties including far-red emission wavelength and fluorescent stability, high quantum yield, and protracted fluorescent decay lifetime. Treatment with LipQDs, rather than free QDs, exhibited high accumulation and retention following intravenous administration in carotid-injured rats (an inflammatory model). QD–monocyte colocalization was detected in the inflamed arterial segment only following treatment with LipQDs. No cytotoxicity was observed following LipQD treatment in cell cultures, and changes in liver enzymes and gross histopathological changes were not detected in mice and rats, respectively. Our results suggest that the LipQD formulation could be a promising strategy for imaging inflammation