Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study.

PURPOSE: To compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model. METHODS: After an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation. RESULTS: At 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%-66%) for PVE versus 23% (IQR: 6%-36%) for TARE after 2 weeks and 51% (IQR: 47%-69%) for PVE versus 29% (IQR: 20%-50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%-119%) for PVE versus 82% (IQR: 70%-96%) for TARE after 3 months and 115% (IQR: 70%-46%) for PVE versus 86% (IQR: 58%-111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139-175) and hypertrophy. CONCLUSIONS: PVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3-6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.

Correcting Concavity of Rabbit Auricular Cartilage: Comparison of Single Scoring Incisions with Butyl Cyanoacrylate-Aided Techniques.

BACKGROUND: The authors present the results of an experimental study in which four different techniques were used for the correction of concave rabbit auricular cartilage. METHODS: Sixteen New Zealand adult male rabbits were used in the study. Butyl cyanoacrylate-aided cartilage graft fixation and butyl cyanoacrylate-aided bone graft fixation and scoring technique, alone or combined with butyl cyanoacrylate application, were performed to correct the concavity of rabbit auricular cartilage. RESULTS: Angle measurements showed that all four techniques were efficient for correction of the cartilage concavities. However, the mean postsacrifice angles of the graft fixation groups were significantly higher than those of the other study groups, reflecting the fact that graft fixation with butyl cyanoacrylate application was more efficient for preserving the final cartilage shape. Furthermore, in the ninth month, graft fixation groups had the lowest chondrocyte densities, the highest degree of inflammation, the highest degree of foreign body reaction, and the highest butyl cyanoacrylate density. CONCLUSIONS: Fibrosis or chondrocyte proliferation on scoring incision lines is not an associated feature of this technique. When the incision depths were standardized, the scoring technique provided efficacy similar to that of the scoring incisions combined with butyl cyanoacrylate application for correction of the cartilage concavity. The scoring incision plus butyl cyanoacrylate group showed less toxicity than the graft fixation groups because of rapid removal of toxic breakdown products. Graft fixation techniques were superior to other corrective procedures with regard to preservation of the final cartilage shape. Although they resulted in greater toxicity, the cartilage correction was not affected unfavorably.

Comparison of 2-Ethyl-Cyanoacrylate and 2-Butyl-Cyanoacrylate for Use on the Calvaria of CD1 Mice.

Short-chain cyanoacrylates (SCCA), such as ethyl-2-cyanoacrylate (KrazyGlue, Aron Alpha, Columbus, OH) are commonly used as commercial fast-acting glues. Although once used in clinical medicine as skin adhesives, these products caused tissue toxicity and thus their use in live tissue was discontinued. SCCA were replaced by longer-chain versions (LCCA), such as butyl-cyanoacrylate (Vetbond, 3M, St Paul, Minnesota), which were found to be less toxic than the short-chain formulations. Some researchers prefer to use SCCA due to the belief that they create a stronger bond than do the longer-chain counterparts. In survival surgeries, we compared the bone thickness, bone necrosis, fibrosis, inflammation, and bone regeneration in the calvaria of control (naïve), surgery-only, SCCA-treated, and LCCA-treated mice (n = 20 per group). At 1 and 14 d after surgery, all mice except those treated with SCCA showed statistically similar bone measurements to those of the naive control group. The SCCA group had significantly less bone regeneration than did all other groups. These results suggest that the application of SCCA causes bone damage resulting in the loss of bone regeneration. This finding may assist investigators in choosing a tissue glue for their studies and may support the IACUC in advocating the use of pharmaceutical-grade tissue glues.

N-butyl cyanoacrylate- and alpha-cyanoacrylate induced hepatotoxicity and venous sclerosis in a rabbit model.

BACKGROUND AND STUDY AIMS: Tissue adhesives are commonly used. The aim of this study was to assess the efficacy and hepatotoxicity of intravenous injection of N-butyl cyanoacrylate versus alpha-cyanoacrylate in a rabbit model. MATERIALS AND METHODS: A total of 20 rabbits were divided into three groups: group I included four rabbits injected with lipiodol in the dorsal vein of a pinna (control group); group II included eight rabbits injected with N-butyl cyanoacrylate/lipiodol; and group III included eight rabbits injected with alpha-cyanoacrylate/lipiodol. All animals were left under normal living conditions for 1week, and then euthanised. Specimens of ear and liver were taken and fixed in 10% formalin saline for histological examination. Secondary fixation was performed using Bouin solution. Specimens of ear were decalcified in ethylenediaminetetraacetic acid (EDTA) at room temperature for 3months. Then, all specimens were processed, embedded in paraffin, sectioned, and stained with haematoxylin and eosin stains for microscopic examination. RESULTS: Microscopic examination of all specimens of the control group revealed normal structure of pinna and liver tissue. Both test groups demonstrated a wide variability of structural changes ranging from oedema and congestion to necrosis and marked cellular inflammatory infiltration. The two groups were compared using a self-designed inflammatory score. This revealed that alpha-cyanoacrylate caused more venous sclerosis with extensive perivenous reaction and hepatotoxicity than both N-butyl cyanoacrylate and control (p<0.05 and p<0.05). N-butyl cyanoacrylate was also found to cause more venous sclerosis and hepatotoxicity than control (p<0.05). CONCLUSION: This study suggested that injection of Krazy Glue, either the clinically usable N-butyl cyanoacrylate or the commercially available alpha-cyanoacrylate, caused comparable venous sclerosis. Unfortunately, both induced significant hepatotoxicity. Therefore, neither of them should be used unless all other safe options are absent. Larger studies have to be conducted and effects of these components on other organs should be investigated; however, caution must be exercised in their clinical use.

Cytotoxicity and apoptotic gene expression in an in vitro model of the blood-brain barrier following exposure to poly(butylcyanoacrylate) nanoparticles.

Background Poly(butylcyanoacrylate) (PBCA) nanoparticles (NPs) loaded with doxorubicin (DOX) and coated with polysorbate 80 (PS80) have shown efficacy in the treatment of rat glioblastoma. However, cytotoxicity of this treatment remains unclear. Purpose The purpose of this study was to investigate cytotoxicity and apoptotic gene expression using a proven in vitro co-culture model of the blood-brain barrier. Methods The co-cultures were exposed to uncoated PBCA NPs, PBCA-PS80 NPs or PBCA-PS80-DOX NPs at varying concentrations and evaluated using a resazurin-based cytotoxicity assay and an 84-gene apoptosis RT-PCR array. Results The cytotoxicity assays showed PBCA-PS80-DOX NPs exhibited a decrease in metabolic function at lower concentrations than uncoated PBCA NPs and PBCA-PS80 NPs. The apoptosis arrays showed differential expression of 18 genes in PBCA-PS80-DOX treated cells compared to the untreated control. Discussion As expected, the cytotoxicity assays demonstrated enhanced dose-dependent toxicity in the DOX loaded NPs. The differentially expressed apoptotic genes participate in both the tumor necrosis factor receptor-1 and mitochondria-associated apoptotic pathways implicated in current DOX chemotherapeutic toxicity. Conclusion The following data suggest that the cytotoxic effect may be attributed to DOX and not the NPs themselves, further supporting the use of PBCA-PS80 NPs as an effective drug delivery vehicle for treating central nervous system conditions.

Comparison of the Toxicities of Ethylene Vinyl Alcohol Copolymer (EVOH) Preparations, Dimethyl Sulphoxide and N-Butyl 2-Cyanoacrylate on Cerebral Parenchyma in an Experimental Rabbit Model.

AIM: Ethylene vinyl alcohol copolymer (EVOH), its organic solvent dimethyl sulfoxide (DMSO), and N-Butyl 2-Cyanoacrylate (NBCA) are widely used in neurovascular embolization procedures and yet with potential risk of cytotoxicity. The aim of this study was to evaluate the toxic effect of EVOH-DMSO, its solvent DMSO and NBCA on cerebral parenchyma in a rabbit model. MATERIAL AND METHODS: Forty-eight albino male rabbits were divided into 6 groups based on the substance injected into the parenchyma; normal saline, DMSO, NBCA, 6% EVOH-DMSO and 20% EVOH-DMSO and control group. At 72 hours the subjects were sacrificed and brain samples were harvested for histopathological examination and lipid peroxidase measurements. RESULTS: Neuronal degeneration and inflammatory reaction in the brain parenchyma was prominent especially in DMSO group and EVOHDMSO groups. Furthermore, the extent of degeneration and inflammatory reaction was related to the concentration of the embolic agent in the EVOH group. Lipid peroxidase activity was significantly increased in the NBCA group as compared to all but to 20 % EVOH-DMSO group. CONCLUSION: EVOH and its solvent DMSO cause degeneration and inflammatory reaction in brain parenchyma and for EVOH this reaction was appeared to be dose dependent.

Preparation, in vitro and in vivo evaluation of polymeric nanoparticles based on hyaluronic acid-poly(butyl cyanoacrylate) and D-alpha-tocopheryl polyethylene glycol 1000 succinate for tumor-targeted delivery of morin hydrate.

Herein, we describe the preparation of a targeted cellular delivery system for morin hydrate (MH), based on a low-molecular-weight hyaluronic acid-poly(butyl cyanoacrylate) (HA-PBCA) block copolymer. In order to enhance the therapeutic effect of MH, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) was mixed with HA-PBCA during the preparation process. The MH-loaded HA-PBCA "plain" nanoparticle (MH-PNs) and HA-PBCA/TPGS "mixed" nanoparticles (MH-MNs) were concomitantly characterized in terms of loading efficiency, particle size, zeta potential, critical aggregation concentration, and morphology. The obtained MH-PNs and MH-MNs exhibited a spherical morphology with a negative zeta potential and a particle size less than 200 nm, favorable for drug targeting. Remarkably, the addition of TPGS resulted in about 1.6-fold increase in drug-loading. The in vitro cell viability experiment revealed that MH-MNs enhanced the cytotoxicity of MH in A549 cells compared with MH solution and MH-PNs. Furthermore, blank MNs containing TPGS exhibited selective cytotoxic effects against cancer cells without diminishing the viability of normal cells. In addition, the cellular uptake study indicated that MNs resulted in 2.28-fold higher cellular uptake than that of PNs, in A549 cells. The CD44 receptor competitive inhibition and the internalization pathway studies suggested that the internalization mechanism of the nanoparticles was mediated mainly by the CD44 receptors through a clathrin-dependent endocytic pathway. More importantly, MH-MNs exhibited a higher in vivo antitumor potency and induced more tumor cell apoptosis than did MH-PNs, following intravenous administration to S180 tumor-bearing mice. Overall, the results imply that the developed nanoparticles are promising vehicles for the targeted delivery of lipophilic anticancer drugs.

Nanotoxicity of poly(n-butylcyano-acrylate) nanoparticles at the blood-brain barrier, in human whole blood and in vivo.

Therapy of diseases of the central nervous system is a major challenge since drugs have to overcome the blood-brain barrier (BBB). A powerful strategy to enhance cerebral drug concentration is administration of drug-loaded poly(n-butylcyano-acrylate) (PBCA) nanoparticles coated with polysorbate 80 (PS80). This study evaluates the toxicity of PBCA-nanoparticles at the BBB, representing the target organ, the inflammatory response in human whole blood, as the site of administration and in a rat model in vivo. PBCA-nanoparticles were prepared by a mini-emulsion method and characterized concerning size, surface charge, shape and PS80-adsorption. The influence on metabolic activity, cell viability and integrity of the BBB was analyzed in an in vitro model of the BBB. In ex vivo experiments in human whole blood the release of 12 inflammatory cytokines was investigated. In addition, the inflammatory response was studied in vivo in rats and complemented with the analysis of different organ toxicity parameters. PBCA-nanoparticles showed time- and concentration-dependent effects on metabolic activity, cell viability and BBB integrity. No cell death or loss of metabolic activity was observed for nanoparticle-concentrations ≤500µg/ml up to 3h of treatment. Within 12 tested inflammatory cytokines, only interleukin-8 displayed a significant release after nanoparticle exposure in human blood. No severe inflammatory processes or organ damages were identified in rats in vivo. Thus, PBCA-nanoparticles are a promising drug delivery system to overcome the BBB since they showed hardly any cytotoxic or inflammatory effect at therapeutic concentrations and incubation times.

Rat model of hindlimb ischemia induced via embolization with polyvinyl alcohol and N-butyl cyanoacrylate.

OBJECTIVE: To investigate the feasibility of a rat model on hindlimb ischemia induced by embolization from the administration of polyvinyl alcohol (PVA) particles or N-butyl cyanoacrylate (NBCA). MATERIALS AND METHODS: Unilateral hindlimb ischemia was induced by embolization with NBCA (n = 4), PVA (n = 4) or surgical excision (n = 4) in a total of 12 Sprague-Dawley rats. On days 0, 7 and 14, the time-of-flight magnetic resonance angiography (TOF-MRA) and enhanced MRI were obtained as scheduled by using a 3T-MR scanner. The clinical ischemic index, volume change and degree of muscle necrosis observed on the enhanced MRI in the ischemic hindlimb were being compared among three groups using the analysis of variance. Vascular patency on TOF-MRA was evaluated and correlated with angiographic findings when using an inter-rater agreement test. RESULTS: There was a technical success rate of 100% for both the embolization and surgery groups. The clinical ischemic index did not significantly differ. On day 7, the ratios of the muscular infarctions were 0.436, 0.173 and 0 at thigh levels and 0.503, 0.337 and 0 at calf levels for the NBCA, PVA and surgery groups, respectively. In addition, the embolization group presented increased volume and then decreased volume on days 7 and 14, respectively. The surgery group presented a gradual volume decrease. Good correlation was shown between the TOF-MRA and angiographic findings (kappa value of 0.795). CONCLUSION: The examined hindlimb ischemia model using embolization with NBCA and PVA particles in rats is a feasible model for further research, and muscle necrosis was evident as compared with the surgical model.

In vivo visualisation of nanoparticle entry into central nervous system tissue.

Because the potential neurotoxicity of nanoparticles is a significant issue, characterisation of nanoparticle entry into the brain is essential. Here, we describe an in vivo confocal neuroimaging method (ICON) of visualising the entry of fluorescent particles into the parenchyma of the central nervous system (CNS) in live animals using the retina as a model. Rats received intravenous injections of fluorescence-labelled polybutyl cyanoacrylate nanoparticles that had been synthesised by a standard miniemulsion polymerisation process. We performed live recording with ICON from before and up to 9 days after particle injection and took photomicrographs of the retina. In addition, selective retrograde labelling of the retinal ganglion cells was achieved by stereotaxic injection of a fluorescent dye into the superior colliculus. Using ICON, we observed vascular kinetics of nanoparticles (wash-in within seconds), their passage to the retina parenchyma (within minutes) and their distribution (mainly cellular) under in vivo conditions. For the detection of cell loss--which is important for the evaluation of toxic effects--in another experiment, we semi-quantitatively analysed the selectively labelled retinal neurons. Our results suggest that the dye per se does not lead to neuronal death. With ICON, it is possible to study nanoparticle kinetics in the retina as a model of the blood-brain barrier. Imaging data can be acquired within seconds after the injection, and the long-term fate of cellular uptake can be followed for many days to study the cellular/extracellular distribution of the nanoparticles. ICON is thus an effective and meaningful tool to investigate nanoparticle/CNS interactions.

Development of an acute obstructive hydrocephalus model in rats using N-butyl cyanoacrylate.

PURPOSE: Previous animal models of obstructive hydrocephalus that was frequently combined with subarachnoid inflammation are not suitable for investigating cerebrospinal fluid (CSF) flow between ventricles and cisterns in obstructive hydrocephalus. In this study, we attempted to develop a new animal model for obstructive hydrocephalus in rats sparing subarachnoid space using N-butyl cyanoacrylate (NBCA). METHODS: Hydrocephalus was induced in adult male Sprague-Dawley rats with NBCA (n=15) or with kaolin (n=10). For the NBCA model, a silicone tube was inserted through the foramen of Magendie into the fourth ventricle, into which 20 µL of a mixture of NBCA and ethiodized oil was injected. For the kaolin model, 100 µL of 20% kaolin solution was injected into the cistern magna. The rats in the NBCA and kaolin groups were sacrificed 3 and 21 days after surgery, respectively. RESULTS: Eleven rats in the NBCA group developed hydrocephalus (73.3%), with a 13.3% mortality rate. The kaolin group showed hydrocephalus in eight rats (80%), with a 20% mortality rate. The mean Evans' indices were 0.37 ± 0.02, 0.45 ± 0.04, and 0.53 ± 0.09 in the control, NBCA, and kaolin groups, respectively (p < 0.05). There was no remarkable arachnoid adhesion or inflammatory change of the ventricular wall in the NBCA group. CONCLUSIONS: The NBCA model seems to be a useful animal model for acute obstructive hydrocephalus with preserved subarachnoid CSF pathway. This model can be useful for studying CSF flow between ventricles and cisterns.

Cyanoacrylate in nerve repair: transient cytotoxic effect.

Cyanoacrylate adhesive has been suggested as an alternative to suturing when repairing severed peripheral nerves. The authors examined the cytotoxic effect of ethyl-cyanoacrylate on the human neuroblastoma cell line SH-SY5Y and compared it with the effects of butyl-cyanoacrylate (Histoacryl), an adhesive approved for skin closure. Ethyl-cyanoacrylate or butyl-cyanoacrylate was applied in confluent SH-SY5Y cultures. Immediately, at 24h and at 7, 14, 21 and 28 days, cultures were photographed and analysed digitally. At corresponding intervals, cell death was quantified using a (51)Cr release assay. In cultures exposed to ethyl-cyanoacrylate or butyl-cyanoacrylate, cell death was observed predominantly in conjunction with the adhesive, causing a halo devoid of cells. Surviving cells showed neurodegenerative properties with loss of neuritis and reduction of body size up to 3 days post exposure. The inhibition halo diminished over time in both groups and at 28 days cells reached the margin of the adhesive in the ethyl-cyanoacrylate group. (51)Cr assay indicated significant cell death in exposed cultures, which rapidly decreased during the first 14 days. No significant differences were found between the adhesives. This study demonstrates that ethyl-cyanoacrylate and butyl-cyanoacrylate have a transient cytotoxic effect, which may explain the promising results when using cyanoacrylate for nerve repair.

[Polysorbate-80 modified neurotoxin nanoparticle with its transport and cytotoxicity against blood-brain barrier].

This study was aimed at the transport across blood-brain barrier (BBB) of polysorbate-80 modified neurotoxin loaded polybutylcyanoacrylate nanoparticle (P-80-NT-NP) and its cytotoxicity. An in vitro model of BBB using rat brain microvascular endothelial cells (rBMECs) was established. The cytotoxicity of P-80-NT-NP was measured by the MTT assays, where neurotoxin (NT), nanoparticle (NP), neurotoxin nanoparticle (NT-NP) as control, and the permeability of P-80-NT-NP was determined by using of Millicell insert coculture with rBMECs and fluorescence spectrophotometry. MTT results showed that NT, NP, NT-NP and P-80-NT-NP were avirulent to rBMECs when the concentration of NT was lower than 200 ng x mL(-1). But the cytotoxicity of NP, NT-NP and P-80-NT-NP would be augmented accordingly as concentration increased (P < 0.01), causing obvious reductions of cell survival rate, with no significant difference between them (P > 0.05). When the concentration of NT was 150 ng x mL(-1), the permeability on rBMECs of P-80-NT-NP and NT-NP were both significantly higher than that of NT (P < 0.01), and the permeability of P-80-NT-NP was greater than that of NT-NP (P < 0.05). In conclusion, polysorbate-80 modified neurotoxin nanoparticles can transport across the BBB, while concentration of NT is greater than 200 ng x mL(-1), P-80-NT-NP has a little cytotoxicity against rBMECs.

Evaluation of the toxicity of onyx compared with n-butyl 2-cyanoacrylate in the subarachnoid space of a rabbit model: an experimental research.

INTRODUCTION: The toxic effects of onyx, its solvent dimethyl sulphoxide (DMSO), and n-butyl 2-cyanoacrylate (NBCA) were evaluated after infusion into the subaracnoid space of a rabbit model. METHODS: Each of the two various concentrations of onyx, pure DMSO, NBCA, and normal saline solution were percutaneously infused into the pontocerebellar cisternae of 39 domestic male albino rabbits, after which, the brain stems and medial cerebellar tissues were harvested for biochemical and histopathological studies. RESULTS: The specimens infused in various concentration of onyx, DMSO, and NBCA showed neural tissue necrosis and edema with inflammatory cell infitration in the acute stage. Although the mean values of the lipid peroxidase in the control, saline, and NBCA groups were found to be almost similar, they were found to be low in the onyx and DMSO groups. CONCLUSION: This experimental study suggests that NBCA, and various concentrations of onyx and DMSO have toxic effects on the neural tissues of rabbits when infused into the subarachnoid space.

Intravenous tolerance of a nanoparticle-based formulation of doxorubicin in healthy rats.

A comparative toxicological study of doxorubicin bound to poly(butyl cyanoacrylate) nanoparticles coated with polysorbate 80 was performed in male and female Wistar rats. The drug substance was used as a reference formulation. The formulations were injected intravenously at a therapeutic dose of 6 mg/kg administered either as a single injection or in form of four weekly injections. The animals were followed up for 4 and 40 days (single injection) or 25 and 61 days (multiple injections) for assessment of the dynamics of body weight, hematological parameters, blood biochemical parameters, and urinalysis. Pathomorphological evaluation included macroscopic evaluation and weight measurement of the internal organs. The heart, lung, spleen, testes, and liver were also subjected to the histological evaluation. The overall result of this study suggests that the surfactant-coated nanoparticle formulation of doxorubicin has a favorable toxicological profile. Specifically, this formulation displays a considerably reduced cardio- and testicular toxicity, as compared to a free drug.

Comparison of the bacteriostatic effects, corneal cytotoxicity, and the ability to seal corneal incisions among three different tissue adhesives.

PURPOSE: To compare the bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions among fibrin glue and 2 commercially available cyanoacrylate derivatives: N-butyl cyanoacrylate and methoxypropyl cyanoacrylate. METHODS: The bacteriostatic activities of these tissue glues were verified by measuring the zones of bacterial growth inhibition surrounding the adhesive droplets on agar plates inoculated with Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Escherichia coli, or Mycobacterium chelonae. Corneal cytotoxicity was tested by a direct contact method by using cultured bovine corneal epithelial cells, keratocytes, and corneal endothelial cells challenged with droplets of adhesives. Each of the cells was treated with droplets of adhesives. The ability to seal corneal incisions was verified by calculating the maximum intraocular pressure resistant to leakage of rabbit corneal stab wounds sealed with tissue adhesives. RESULTS: Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate showed bacteriostatic effects against S. aureus, S. pneumoniae, and M. chelonae but not P. aeruginosa and E. coli. In contrast, fibrin glue had no such effects against either Gram-positive or -negative bacteria (P < 0.01). Methoxypropyl cyanoacrylate showed the highest levels of corneal cytotoxicity, followed by N-butyl cyanoacrylate. Fibrin glue, however, showed minimal cytotoxicity (P < 0.01). Methoxypropyl cyanoacrylate and N-butyl cyanoacrylate also displayed a greater ability to seal corneal incisions than that of fibrin glue (P < 0.01). CONCLUSIONS: The bacteriostatic effects, corneal cytotoxicity, and ability to seal corneal incisions differed among the 3 compounds tested. These different properties should be considered when choosing tissue adhesives during corneal surgery.

Biochemical and histopathological findings of N-butyl-2-cyanoacrylate in oral surgery: an experimental study.

OBJECTIVES: The increasing use of cyanoacrylates in dentistry, particularly as an adhesive and sealing glue, has raised concerns regarding its potential toxicity in humans. Several different forms of these compounds including methyl- (MCA), ethyl- (ECA), isobutyl-, isohexyl-, and octyl CA have been developed to eliminate tissue toxicity. N-butyl-2-cyanoacrylate is becoming an increasingly popular method for wound closure under low tension. Despite their increasing use, pharmacologic effects of these substances on liver and kidney functions are not widely known. The objective of the present study was to investigate possible immediate and long-term systemic effects of N-butyl-2-cyanoacrylate in oral surgery. STUDY DESIGN: Ten male Wistar rats weighing 220 to 270 g were used in the study. Straight incisions were made to the buccal mucosa of the animals. N-butyl-2-cyanoacrylate adhesive (Indermil) was applied and wounds were closed primarily. Blood specimens were taken periodically from the vena cava of the animals before the surgical procedure and 2, 14, 21, and 65 days after the surgical procedure. The blood specimens of those taken before the application of the adhesive were defined as the control group; blood specimens that were taken 2, 14, 21, and 65 days from the application were defined as study group. The stored plasma samples were analyzed for blood urea nitrogen (BUN), creatinine (CRE), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBI), total protein (TP), albumin (ALB), and amylase (AML). In addition to biochemical parameters, histopathological examination was performed. Blood parameter values of the control and study groups were statistically compared with the Duncan test (P < .05). RESULTS: There were no significant differences in the values of BUN, CRE, ALT, AST, TBI, TP, ALB, and AML between the control and at 2, 14, 21, and 65 days. CONCLUSION: The present study shows that N-butyl-2-cyanoacrylate is a suitable adhesive applicable in oral surgery.

[Antitumor activity of mitoxantrone-nanosphere against murine liver tumor H22].

OBJECTIVE: [corrected] To make a comparison between mitoxantrone (DHAQ) and liver targeting drug delivery system mitoxantrone-polybutylcyanoacrylate-nanosphere (DHAQ-PBCA-NS) in respect to their antitumor activity against experimental liver tumor H22 in mice. METHODS: Drugs were given intravenously on the 1st, 5th, 9th day after planting tumor respectively. Weight of tumor in mouse was determined and the results were compared with those of mitoxantrone (DHAQ). RESULTS: There was relationship of dose-effect for both DHAQ and DHAQ-PBCA-NS, and the median effective dose (ED50) of DHAQ and DHAQ-PBCA-NS was 1.04 mg/kg and 0.34 mg/kg respectively. The lethal dose to 50% of the population (LD50) of DHAQ and DHAQ-PBCA-NS i.v. in mice with the same administration schedule was 3.670 mg/kg and 4.225 mg/kg respectively. Therefore, the calculated value of therapeutic index was 3.53 for DHAQ and 12.43 for DHAQ-PBCA-NS. In addition, the antitumor activity of both drugs with different treatment schedules was reported. The results showed: the earlier the mice were treated, the higher the antitumor activity of the two drugs were seen. However, DHAQ-PBCA-NS presented higher activity than DHAQ did, when the same treatment schedule was followed. CONCLUSION: The results demonstrated that the antitumor activity of DHAQ-PBCA-NS is much higher than that of DHAQ, and DHAQ-PBCA-NS is possessed of liver targeting property.

Cytotoxic effects of cyanoacrylates used as retrograde filling materials: an in vitro analysis.

Cyanoacrylate has been used in medicine and dentistry for many years. It has been used as a postextraction dressing and retrograde filling material in endodontic surgery. The aim of this study was to evaluate the cytotoxic effects of Histoacryl and other two homologue ethyl cyanoacrylates, Super Bonder and Ultrabond, on cultured fibroblasts, using the Trypan blue dye exclusion assay. The cyanoacrylates were applied to round glass coverslips, which were placed in contact with NIH 3T3 cells. After 0, 6, 12 and 24 h (short-term assay; viability) and 1, 3, 5 and 7 days (long-term assay; survival), the cells were examined under phase light microscopy and counted. The data were compared by the Kruskal-Wallis test. In the short-term experiments, only the cultures of the Ultrabond group (GIV) presented significant smaller percentages of cell viability than the cultures of the other groups (GI: control; GII: Super Bonder; GIII: Histoacryl). Although the cultures of the Super Bonder group (GII) presented smaller percentages of cell viability than cultures of the other groups (GI, GIII, GIV) at the long-term assay, this group was the only experimental group presenting a continuous and progressive cell growth. Our results have shown an in vitro biocompatibility of Histoacryl and ethyl cyanoacrylate homologues. These cyanoacrylates could therefore be of importance for endodontic purposes.