Isobutylcyanoacrylate Research Articles

In Vitro Efficacy of Isobutyl Cyanoacrylate Nanoparticles against Fish Bacterial Pathogens and Selection Preference by Rainbow Trout (Oncorhynchus mykiss).

The upsurge in havoc being wreaked by antibiotic-resistant bacteria has led to an urgent need for efficacious alternatives to antibiotics. This study assessed the antibacterial efficacy of two isobutyl cyanoacrylate nanoparticles (iBCA-NPs), D6O and NP30, against major bacterial pathogens of fish. In vivo tests on rainbow trout were preceded by in vitro tests of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). NP30 exhibited higher efficacy than D60, but both iBCA-NPs demonstrated dose-dependent and species-specific in vitro antibacterial properties against the bacterial isolates. Generally, Gram-negative bacteria were more resistant to the iBCA-NPs. Streptococcus iniae, Tenacibaculum maritimum, and Photobacterium damselae were particularly sensitive to both iBCA-NPs. Administered to rainbow trout at 3571.4 mg (iBCA-NP)/kg feed, the iBCA-NPs produced a relative gain rate and survival rates comparable to the control (p > 0.05). The condition factor and the hepatosomatic and viscerosomatic indices of fish were indifferentiable (p > 0.05) between the iBCA-NP groups and the control. The iBCA-NPs caused no alteration in stress, oxidative stress (superoxide dismutase, SOD), plasma complement titer, or lysozyme activity. This study presents the first report of antibacterial activity of iBCA-NPs against Gram-negative bacteria. The results of this study suggest that D60 and NP30 may contribute to reducing the amounts of antibiotics and chemotherapeutic agents used in aquaculture.

Treatment of orbital vascular malformations with intralesional bleomycin injection and N-butyl-2-cyanoacrylate glue embolization

Objective: To evaluate the clinical efficacy of bleomycin lavage combined with N-butyl-2-cyanoacrylate glue embolization and resection in the treatment of orbital vascular malformations. Methods: It was a retrospective case series study. Patients with orbital vascular malformations diagnosed at the Ophthalmology Division of Chinese PLA General Hospital from January 2018 to October 2021 were included and divided into exophthalmos group and non-exophthalmos group based on whether the patients had postural exophthalmos. Intralesional bleomycin injection and N-butyl-2-cyanoacrylate glue embolization were performed. The preoperative and postoperative visual acuity, the dosages of bleomycin and isobutyl cyanoacrylate glue, pathological results, imaging findings and remission rate were recorded and analyzed. The Chi-square test, Wilcoxon signed rank analysis and Mann-Whitney U test were used for statistical analysis. Results: A total of 58 patients (58 eyes)were included, and there were 22 males (37.9%) and 36 females (62.1%). Nineteen (32.8%) patients had postural exophthalmos, and 39 (67.2%) patients did not suffer postural exophthalmos. The patient's age of the two groups was 39.0 (28.0, 54.5) years vs. 14.0 (5.7, 26.5) years, with a statistically significant difference (Z=-3.96, P<0.001). There was no significant difference in gender, eye laterality, follow-up time and the disease course between the two groups (all P>0.05). During the operation, the dosage of bleomycin was 15 000 (13 500, 15 000) U in the exophthalmos group, and 15 000 (9 000, 16 500) U in the non-exophthalmos group (Z=-0.70, P=0.944). The dosages of N-butyl-2-cyanoacrylate glue were 2.8 (1.0, 3.0) ml and 1.7 (1.0, 2.2) ml, respectively, in the two groups, with no significant difference (Z=-1.11, P=0.268). There was no visual impairment in both groups, while the visual acuity in 5 patients without postural exophthalmos was improved postoperatively. The imaging examination results showed no difference in the malformed vascular area before and after the treatment in the exophthalmos group [384.0 (329.0, 458.0) mm2 vs. 330.5 (271.6, 356.7) mm2; Z=-1.26, P=0.208], but a significantly decreased area after the treatment in the non-exophthalmos group [960.8 (822.1, 1058.3) mm2 vs. 311.6 (164.6, 361.6) mm2; Z=-2.67, P=0.008]. All patients had no obvious local or systemic adverse reactions during the follow-up. The pathology reports showed vascular malformations in all 15 specimens obtained from the exophthalmos group, as well as vascular malformations in 41.0% (16/39) of specimens and venous lymphatic malformations in 59.0% (23/39) of specimens from the non-exophthalmos group. Thirty-nine patients had complete remission (67.2%), 19 patients had partial remission (32.8%), and the effective treatment rate was 100%. Conclusion: Bleomycin lavage combined with N-butyl-2-cyanoacrylate glue embolization can achieve good therapeutic effects on orbital vascular malformations.

Chronological transcriptome changes induced by exposure to cyanoacrylate resin nanoparticles in Chlamydomonas reinhardtii with a focus on ROS development and cell wall lysis-related genes

Resin nanoparticles composed of isobutyl cyanoacrylate polymers (iBCA-NPs) are reported to induce acute cell death in many microalgal species. Chronological transcriptome changes induced by exposure to iBCA-NPs in Chlamydomonas reinhardtii (Chlorophyceae) were investigated using next-generation sequencing. Genes encoding antioxidant enzymes, such as glutathione peroxidase (GPX5), Fe-superoxide dismutase (Fe-SOD), and glutathione S-transferase (GSTS1), were prominently upregulated when the cell death ratio reached approximately 3 %. Subsequently, strong expression of these genes was maintained even when the cell death ratio reached ~30 %. Apart from these genes, nine out of 20 heat shock protein (HSP)-coding genes were also upregulated. There was a positive correlation between cell death and ROS accumulation. Upregulation of these genes must be a response to cope with the stresses induced by the ROS accumulation.Cre13.g605200, which is one of 31 genes annotated to encode cell wall hydrolytic enzymes, was highly upregulated by exposure to iBCA-NPs. Three tag-insertion mutants of the Cre13.g605200 gene showed considerably more resistance to cell wall hydrolysis and nanoparticle-induced cell death than the parent strain, suggesting that the Cre13.g605200 gene encodes a cell wall hydrolytic enzyme, and that its upregulation contributes to acute cell death induced by the iBCA-NPs. Positive contribution of the Cre13.g605200 to cell death suggests that the target of nanoparticles (NPs) to induce cell death is located inside the cell walls.The laddering DNA of nucleosome units, a hallmark of programmed cell death (PCD), was barely detectable in the smeared DNA of C. reinhardtii cells exposed to iBCA-NPs. This shows that necrosis-like cell death is the most common type of induced cell death caused by iBCA-NPs exposure. Induced cell death can be the result of intracellular damage to proteins, lipids and DNA caused by ROS.

Evaluation of the Growth-Inhibitory Spectrum of Three Types of Cyanoacrylate Nanoparticles on Gram-Positive and Gram-Negative Bacteria.

The development of novel effective antibacterial agents is crucial due to increasing antibiotic resistance in various bacteria. Poly (alkyl cyanoacrylate) nanoparticles (PACA-NPs) are promising novel antibacterial agents as they have shown antibacterial activity against several Gram-positive and Gram-negative bacteria. However, the antibacterial mechanism remains unclear. Here, we compared the antibacterial efficacy of ethyl cyanoacrylate nanoparticles (ECA-NPs), isobutyl cyanoacrylate NPs (iBCA-NPs), and ethoxyethyl cyanoacrylate NPs (EECA-NPs) using five Gram-positive and five Gram-negative bacteria. Among these resin nanoparticles, ECA-NPs showed the highest growth inhibitory effect against all the examined bacterial species, and this effect was higher against Gram-positive bacteria than Gram-negative. While iBCA-NP could inhibit the cell growth only in two Gram-positive bacteria, i.e., Bacillus subtilis and Staphylococcus aureus, it had negligible inhibitory effect against all five Gram-negative bacteria examined. Irrespective of the differences in growth inhibition induced by these three NPs, N-acetyl-L-cysteine (NAC), a well-known reactive oxygen species (ROS) scavenger, efficiently restored growth in all the bacterial strains to that similar to untreated cells. This strongly suggests that the exposure to NPs generates ROS, which mainly induces cell growth inhibition irrespective of the difference in bacterial species and cyanoacrylate NPs used.

Fucoidan-coated PIBCA nanoparticles containing oncocalyxone A: Activity against metastatic breast cancer cells

BackgroundOncocalyxone A (oncoA) is a natural benzoquinone isolated from Cordia oncocalyx, which exhibits many biological activities such as anti-tumor, anti-inflammatory, antioxidant, and hypoglycemic. However, it presents renal, cardiac, and pulmonary toxicity, which can be a limiting factor. The encapsulation of oncoA in polymeric nanoparticles can enhance its therapeutic effect, while reducing its toxicity. ObjectiveThus, this study aimed to develop nanoparticles of poly (isobutyl cyanoacrylate) containing oncoA, and to evaluate its activity against metastatic breast cancer cells. MethodsThe nanoparticles were obtained using the anionic emulsion polymerization technique and characterized by Fourier-transform Infrared spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Energy Dispersive X-Ray Analysis (EDX), Differential Scanning Calorimetry (DSC), and Thermogravimetry (TG), in addition to studies of long-term stability, including different pH, and blood compatibility. Antiproliferative activity was assessed by MTT and cell migration assays. ResultsThe nanoparticles were obtained with a particle size of 305 ± 6.49 nm and encapsulation rate of 101.5 ± 1.4%, and were stable at different pH over 7 months. The nanoparticles did not induce hemolysis. The encapsulation of oncoA in fucoidan-coated PIBCA nanoparticles increased its cytotoxicity on MDA-MB-231 cells, and inhibited cell migration. ConclusionIn conclusion, fucoidan-coated PIBCA nanoparticles containing oncoA may be a promising alternative for further anticancer in vivo studies.

Mucoadhesive paclitaxel-loaded chitosan-poly (isobutyl cyanoacrylate) core-shell nanocapsules containing copaiba oil designed for oral drug delivery

The development of drug delivery systems for potent anticancer drugs like paclitaxel remains a challenger. The aim of this work was to study the mucoadhesive properties of paclitaxel-loaded chitosan-poly (isobutyl cyanoacrylate) core-shell nanocapsules designed for oral drug delivery. Using an experimental design approach, the nanocapsules were produced and, then, physicochemically characterized. Mucoadhesion assays were performed in-vitro by the aggregation test with mucin and ex-vivo, in Ussing Chamber, using freshly excised rat intestinal mucosa. [3H]-paclitaxel dosages were carried out by liquid scintillation. Paclitaxel-loaded nanocapsules showed a mean hydrodynamic diameter of 470 nm with low polydispersity index and spherical form. Encapsulation efficiency and drug loading of paclitaxel were 74 ± 1% and 1.70 ± 0.02%, respectively. After drying, nanocapsules could be redispersed with no changes on their nanostructure. Dispersions of nanocapsules were stable in simulated gastric medium for 120 min, and after six months of storage at 4 °C. They showed interesting mucoadhesive properties with mucins and good association (9%) with the intestinal mucosa of the rat. Taking together, results from the present work are encouraging to pursue the development of chitosan-coated nanocapsules for oral delivery of paclitaxel as a new treatment for cancer with possible synergetic anticancer effect with the therapeutically active components found in copaiba oil.

Theoretical study on the stability of insulin within poly-isobutyl cyanoacrylate (PIBCA) nanocapsule

ABSTRACTTo study the physical stability of insulin in drug delivery particles, we developed a coarse-grained (CG) model for insulin based on dissipative particle dynamics (DPD). Three insulin modelling schemes were considered: each amino acid as a bead (IM1), each amino acid being separated into one to three beads (IM2), and adding secondary structural information of insulin to IM2 (IM3). The best possible bead-bead interaction parameters were obtained from Hildebrand and Hansen solubility parameters by performing the constant-temperature DPD simulation with insulin models in 20% acetic acid solution. IM3 showed good results in terms of RMSF, RMSD and A1B30 distance compared to those of all-atom models from the literature. Then, the IM3 model was considered in an oil-filled poly (isobutyl cyanoacrylate) (PIBCA) nanocapsule. Two crucial factors were found that mainly influence the stability of insulin in oil: the PIBCA shell thickness and the amount of ethanol in the oil droplet. An appropriate PIBCA shell thickness is necessary to block the interaction between insulin and water outside, and ethanol could stabilise insulin with its good affinity for both insulin and oil.

Mucoadhesive properties of low molecular weight chitosan- or glycol chitosan- and corresponding thiomer-coated poly(isobutylcyanoacrylate) core-shell nanoparticles

The aim of the present work was to evaluate the mucoadhesive properties of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles (NPs) coated with Low Molecular Weight (LMW) chitosan (CS)- and glycol chitosan (GCS)-based thiomers as well as with the corresponding LMW unmodified polysaccharides. For this purpose, all the CS- and GCS-based thiomers were prepared under simple and mild conditions starting from the LMW unmodified polymers CS and GCS. The resulting NPs were of spherical shape with diameters ranging from 400 to 600nm and 187 to 309nm, for CS- and GCS-based NPs, respectively. The mucoadhesive characteristics of these core shell NPs were studied in Ussing chambers measuring the percentage of NPs stuck on the mucosal of fresh intestinal tissue after 2h of incubation. Moreover, incubation of nanoparticle formulations with the intestinal tissue induced changes in transmucosal electrical resistance which were measured to gain information into the opening of tight junctions and to control the integrity of the mucosa. Thus, it was found that PIBCA NPs coated with the GCS–Glutathione conjugate (GCGPIBCA NPs) possessed the most favorable mucoadhesive performances. Moreover, both GCGPIBCA- and GCS-N-acetyl-cysteine (GCNPIBCA)-core-shell NPs might induced an enlargement of the epithelial cell tight junctions. In conclusion, coating of PIBCA NPs with GCS-based thiomers may be useful for improving the mucoadhesive and permeation properties of these nanocarriers.

Inflammation Caused by Nanosized Delivery Systems: Is There a Benefit?

Secondary macrophage cytotoxicity induced by nanoparticles was described before. The study aim was to investigate the role of secondary cytotoxic effect in a macrophage-lung cancer coculture model after nanoparticle treatment in the presence and absence of anti-inflammatory drugs. An in vitro coculture model composed of confluent alveolar macrophage MH-S and A-549 lung cancer cells separated by a 0.4 μm porous membrane was used in the study. Macrophages were treated with two sizes of gelatin nanoparticles and two sizes of poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles, with and without doxorubicin as a chemotherapeutic drug. The treatment effect with and without the presence of anti-inflammatory drug was studied using an MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The model drugs were ibuprofen, celecoxib, prednisolone, dexamethasone, and methotrexate. Different nanoparticles in different sizes were synthesized with a range of physicochemical characteristics. Doxorubicin loaded nanoparticles were prepared with an entrapment efficiency of 82-83% for PIBCA and 39-42% for gelatin. Nanoparticle treatment of macrophages showed a secondary cytotoxic effect on A-549 cancer cells at 24 and 36 h, with a drop in cell viability of 40-62%. However, this effect was significantly reduced to 10-48% if the macrophages were exposed to anti-inflammatory drugs. When ibuprofen and celecoxib were used the cell viability rebounded between 24 and 36 h. For prednisolone, dexamethasone, and methotrexate the cell viability dropped further between 24 and 36 h. Macrophages exposed to nanoparticles show secondary cytotoxicity, which has a significant antitumor effect in the microclimate of the coculture model. The beneficial nanoparticle treatment effect was significantly reduced if nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticoids, or methotrexate was given at the same time. The data suggest that anti-inflammatory treatments can decrease the carrier-induced macrophage cytotoxicity and its antitumor effectiveness with chemotherapy.

Superselective transcatheter arterial embolization in patients with acute peripancreatic bleeding complications: review of 44 cases.

To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications. During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n=38), polyvinyl alcohol (PVA) particles (n=2), isobutyl cyanoacrylate (n=2), coils plus PVA particles (n=1), and coils plus isobutyl cyanoacrylate (n=1). Outcome measures included technical success, clinical success, and the rate of complications. Identified bleeding sources included gastroduodenal artery (n=14), splenic artery (n=9), pancreaticoduodenal artery (n=6), common hepatic artery (n=5), superior mesenteric artery branches (n=4), proper hepatic artery (n=3), and dorsal/transverse pancreatic artery (n=3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93%). Clinical success attributed to TAE alone was documented in 40/44 patients (91%). The rate of major complications was 2% including death in one patient. Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications.

Microcalorimetric Method to Assess Phagocytosis: Macrophage-Nanoparticle Interactions

This study evaluated the use of isothermal microcalorimetry (ITMC) to detect macrophage-nanoparticle interactions. Four different nanoparticle (NP) formulations were prepared: uncoated poly(isobutyl cyanoacrylate) (PIBCA), polysorbate-80-coated PIBCA, gelatin, and mannosylated gelatin NPs. Changes in NP formulations were aimed to either enhance or decrease macrophage-NP interactions via phagocytosis. Alveolar macrophages were cultured on glass slabs and inserted in the ITMC instrument. Thermal activities of the macrophages alone and after titration of 100 μL of NP suspensions were compared. The relative interactive coefficients of macrophage-NP interactions were calculated using the heat exchange observed after NP titration. Control experiments were performed using cytochalasin B (Cyto B), a known phagocytosis inhibitor. The results of NP titration showed that the total thermal activity produced by macrophages changed according to the NP formulation. Mannosylated gelatin NPs were associated with the highest heat exchange, 75.4 ± 7.5 J, and thus the highest relative interactive coefficient, 9,269 ± 630 M-1. Polysorbate-80-coated NPs were associated with the lowest heat exchange, 15.2 ± 3.4 J, and the lowest interactive coefficient, 890 ± 120 M-1. Cyto B inhibited macrophage response to NPs, indicating a connection between the thermal activity recorded and NP phagocytosis. These results are in agreement with flow cytometry results. ITMC is a valuable tool to monitor the biological responses to nano-sized dosage forms such as NPs. Since the thermal activity of macrophage-NP interactions differed according to the type of NPs used, ITMC may provide a method to better understand phagocytosis and further the development of colloidal dosage forms.

Secondary cytotoxicity mediated by alveolar macrophages: A contribution to the total efficacy of nanoparticles in lung cancer therapy?

Local treatment of lung cancer using inhalable nanoparticles (NPs) is an emerging and promising treatment option. The aim of this study was to investigate the activation of alveolar macrophages by poly (isobutyl cyanoacrylate) (BIPCA) NPs and the consequences of this activation on H460 lung cancer cells. A methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was used to determine the primary cytotoxicity, that is, the immediate and direct cytotoxicity of doxorubicin (DOX)-loaded NPs on both cell lines. Macrophages were then treated using EC 50 concentrations of different treatments and co-cultured in a two-compartment system with H460 lung cancer cells. These treatments included DOX solution, blank NPs, and DOX-loaded NPs. The results showed that alveolar macrophages exposed to blank or DOX-loaded NPs showed cytotoxicity against cancer cells after 8 and 24 h; this behavior was not expressed by naïve macrophages or macrophages treated with DOX solution. Sample analysis indicated that macrophages have the ability to release back fragments of NPs that were previously phagocytized. Further investigations showed that NPs can induce an increase in the excretion of Th1 cytokines namely, monocytes chemoattractant protein-1 (MCP-1), macrophages inflammatory protein (MIP-1), tumor necrosis factor α (TNF-α), and interferon gamma (IFN-γ). The Th1 cytokines released by the alveolar macrophages might explain the significant secondary cytotoxicity effect on H460 cancer cells. Secondary cytotoxicity mediated by macrophages might compliment the direct cytotoxic effect that NPs have on cancer cells.

Specific permeability modulation of intestinal paracellular pathway by chitosan-poly(isobutylcyanoacrylate) core-shell nanoparticles

This work is focused on the evaluation of the in vitro permeation modulation of chitosan and thiolated chitosan (chitosan-TBA) coated poly(isobutylcyanoacrylate) (PIBCA) nanoparticles as drug carriers for mucosal administration. Core-corona nanoparticles were obtained by radical emulsion polymerisation of isobutylcyanoacrylate (IBCA) with chitosan of different molecular weights and different proportions of chitosan/chitosan-TBA. In this work, the effect of these nanoparticles on the paracellular permeability of intestinal epithelium was investigated using the Ussing chamber technique, by adding nanoparticle suspensions in the mucosal side of rat intestinal mucosa. Results showed that permeation of the tracer [ 14C]mannitol and the reduction of transepithelial electrical resistance (TEER) in presence of nanoparticles were more pronounced in those formulations prepared with intermediate amounts of thiolated polymer. This effect was explained thanks to the high diffusion capacity of those nanoparticles through the mucus layer that allowed them to reach the tight junctions in higher extent. It was concluded that, although a first contact between nanoparticles and mucus was a mandatory condition for the development of a permeation enhancement effect, the optimal effect depended on the chitosan/chitosan-TBA balance and the conformational structure of the particles shell.

In vitro evaluation of calcium binding capacity of chitosan and thiolated chitosan poly(isobutyl cyanoacrylate) core–shell nanoparticles

The ability of chitosan and its derivatives to bind cations is well known. Chitosan and thiolated chitosan were recently associated with poly(isobutyl cyanoacrylate) (PIBCA) nanoparticles leading to very promising results in terms of bioadhesion and permeation enhancement properties. Taking into account the influence that cations concentration have in the maintenance of both the permeation and the enzymatic barrier of the oral route, the possible cation binding capacity of these colloidal systems might be interesting in the use of these nanocarriers for the oral administration of pharmacologically active peptides. The aim of the present work was to in vitro evaluate the capacity of these colloidal systems to bind calcium, a model cation of physiological interest in the intestinal tract. The presence of chitosan on the nanoparticle surface importantly increased the calcium binding ability, in comparison to non-coated PIBCA nanoparticles. In addition, its presentation in the gel layer surrounding the nanoparticles, also beneficiated its binding capacity, obtaining 2–3 folds higher values when the polymer coated the nanoparticles than when it was in solution. The cross-linked structure observed for thiolated chitosan, due to the formation of inter- and intra-chain disulphide bonds, diminished the accessibility of cation to active sites of the polymer, decreasing the binding capacity of the calcium ion. However, when the amount of free thiol groups on the nanoparticle surface was high enough, the binding behaviour observed was higher than for nanoparticles elaborated with non-modified polymer.

Mucoadhesion mechanism of chitosan and thiolated chitosan-poly(isobutyl cyanoacrylate) core-shell nanoparticles

The study is focused on the evaluation of the potential bioadhesive behaviour of chitosan and thiolated chitosan (chitosan-TBA)-coated poly(isobutyl cyanoacrylates) (PIBCA) nanoparticles. Nanoparticles were obtained by radical emulsion polymerisation with chitosan of different molecular weight and with different proportions of chitosan/chitosan-TBA. Mucoadhesion was ex vivo evaluated under static conditions by applying nanoparticle suspensions on rat intestinal mucosal surfaces and evaluating the amount of nanoparticles remaining attached to the mucosa after incubation. The analysis of the results obtained demonstrated that the presence of either chitosan or thiolated chitosan on the PIBCA nanoparticle surface clearly enhanced the mucoadhesion behaviour thanks to non-covalent interactions (ionic interaction and hydrogen bonds) with mucus chains. Both, the molecular weight of chitosan and the proportion of chitosan-TBA in the formulation influenced the nanoparticle hydrodynamic diameter and hence their transport through the mucus layer. Improved interpenetration ability with the mucus chain during the attachment process was suggested for the chitosan of high molecular weight, enhancing the bioadhesiveness of the system. The presence of thiol groups on the nanoparticle surface at high concentration (200×10 −6 μmol SH/cm 2) increased the mucoadhesion capacity of nanoparticles by forming covalent bonds with the cysteine residues of the mucus glycoproteins.

Tuning of shell and core characteristics of chitosan-decorated acrylic nanoparticles

The aim of the work was to develop a new family of chitosan-coated acrylic nanoparticles to increase the specificity of absorption of drugs associated given by the mucosal route. To achieve this goal, techniques of radical and anionic emulsion polymerisation of isobutylcyanoacrylate (IBCA) were used. Changes in the shell composition were made by using chitosan of different molecular weight and thiolated chitosan to modify the particle surface properties in order to vary the mucosae–nanoparticle interactions. The core was also modified by the inclusion of methyl methacrylate (MMA) as second monomer potentially able to improve the control of drug release. Finally, the labelling of nanoparticles core with a fluorophore, methacryloxyethyl thiocarbamoyl rhodamine B (Polyfluor™), was successfully achieved, necessary for the in vitro and in vivo evaluation of the systems created. Results showed that nanoparticle size varied from 200 to 500 nm, depending on the molecular weight of chitosan used. Positive surface charge values were obtained in all cases. In addition, evidences of the presence of thiol groups were obtained (0.03–0.16 × 10 −3 μmol/cm 2 of nanoparticle).

Busulfan loading into poly(alkyl cyanoacrylate) nanoparticles: Physico‐chemistry and molecular modeling

The busulfan is an alkylating agent widely used for the treatment of haematological malignancies and nonmalignant disorders. For a long time, it has been available only in an oral form. This treatment leads to a wide variability in bioavailability and side effects such as the veino-occlusive disease. Thus, an intravenous formulation of busulfan-loaded nanoparticles may be considered as a major progress. This study deals with busulfan entrapment by nanoprecipitation into five different types of poly(alkyl cyanoacrylate) polymers. The polymers leading to the highest busulfan loading efficiencies were poly(isobutyl cyanoacrylate) (PIBCA) and poly(ethyl cyanoacrylate). Molecular modeling along with energy minimization process was employed to identify the nature of the interactions occurring between busulfan and PIBCA. Further, optimization studies enabled to obtain PIBCA nanoparticles displaying busulfan loading ratios equal to 5.9% (w/w) together with nanoparticle yields of 71% (w/w). Since busulfan is a highly reactive molecule, we performed (1)H-NMR spectroscopy experiments showing that chemical integrity of the drug was preserved after loading into nanoparticles. The in vitro release studies under sink conditions, in water, or in rat plasma showed a fast release in the first 10 min followed by a slower one over 6 h. This phenomenon could be explained by the semi-polar characteristics of busulfan.

Endovascular Treatment of Arterial Injury as an Uncommon Complication after Orthopedic Surgery

To evaluate selective and superselective catheter therapy of serious arterial damage associated with orthopedic surgery of the pelvis, hip joint, femur, and knee. Between 1989 and 2005, 16 consecutive patients with arterial damage after orthopedic surgery (seven women, nine men; mean age, 62 years; age range, 21-82 y) underwent angiographic exploration. Seven patients were in hemodynamically unstable condition. Initial orthopedic procedures were iliac crest internal fixation (n = 1); total hip prosthesis (n = 3); revision of total hip prosthesis (n = 4); revision of acetabular cup prosthesis (n = 1); gamma-nailing, nail-plate fixation, or intramedullary nailing (n = 3); and total knee prosthesis (n = 4). Angiography showed pseudoaneurysms (n = 11), vascular lacerations with active extravasation (n = 3), and arteriovenous fistulas with extravasation (n = 2). After angiographic documentation of serious arterial injury, 14 patients were treated with a single or coaxial catheter technique in combination with coils alone, coils and polyvinyl alcohol particles, coils and Gelfoam pledgets, or Gelfoam pledgets; or balloon occlusion with isobutyl cyanoacrylate and coils. Two patients were treated with covered stents. In all, bleeding was effectively controlled in a single session in 16 patients, with immediate circulatory stabilization. Major complications included death, pulmonary embolism, and postprocedural hematoma. Selective and superselective catheter therapy may be used for effective, minimally invasive management of rare but potentially life-threatening vascular complications after orthopedic surgery.

Tissue reactions induced by different embolising agents in cerebral arteriovenous malformations: a histopathological follow-up

Comparative histopathological analysis was performed in 47 incompletely embolised and resected cerebral arteriovenous malformations (AVMs). Thirty-three AVMs were embolised with n-butyl-cyanoacrylate (NBCA), four with iso-butyl-cyanoacrylate (IBCA), seven with polyvinyl alcohol particles (PVA), one with a fibrin mixture, one with silicon pellets, and one with microcatheter balloons. Maximum exposure time (MET) of the embolising agent (interval between embolisation and surgery) ranged from <24 hours to 80 months. All AVMs were investigated regarding angionecrosis, angiofibrosis, acute inflammation, chronic inflammation, foreign-body reactions, vascular calcification, blood admixture to embolising cast, and capillary recanalisation within the AVMs. These parameters were correlated with MET, comparing different embolising agents, age, and sex. A typical sequence of events depending on MET is observed in all embolised AVMs: acute inflammation with mural angionecrosis is soon replaced by prominent chronic granulomatous vasculitis, which remains stable and is detectable for a very long time, even in AVMs with a MET of more than 6 years. Capillary recanalisation is always present in incompletely embolised AVMs, detectable after 3 months of MET, irrespective of the embolising agent used. Age and sex does not influence pattern and time course of tissue lesions and recanalisation in incompletely embolised AVMs.

Isobutyl cyanoacrylate as a tissue adhesive. An experimental study

Journal Article Isobutyl cyanoacrylate as a tissue adhesive. An experimental study Get access J Hale, J Hale Surgical Unit, Westminster Hospital, London Search for other works by this author on: Oxford Academic Google Scholar Harold Ellis Harold Ellis Surgical Unit, Westminster Hospital, London Search for other works by this author on: Oxford Academic Google Scholar British Journal of Surgery, Volume 55, Issue 11, November 1968, Pages 850–852, https://doi.org/10.1002/bjs.1800551111 Published: 08 December 2005