Poly Isobutylcyanoacrylate Nanoparticles Research Articles

Development of levan-coated PIBCA nanoparticles and their antiproliferative activity against MDA-MB-231 and B16F10 cells

Polysaccharides have been described as a successful alternative in developing nanosystems to reach specific sites. Levan is an exopolysaccharide with several biological activities, including immunostimulant, blood plasma substitute, and drug action prolonging agent. The present work aimed to develop poly-isobutyl cyanoacrylate (PIBCA) nanoparticles coated levan (Np-Lev) and to verify its cytotoxicity in two cancer cell lines. Levan was obtained through the fermentation of ZAG 12 Zymomonas mobilis. The nanoparticles were prepared using the anionic emulsion polymerization technique and characterized in size, zeta potential, morphological analysis, X-ray diffraction, infrared spectroscopy, and thermogravimetric analysis. The cell lines MDA-MB-231 (metastatic breast cancer cells) and B16F10 (melanoma cells) were used to evaluate the antiproliferative activity and cellular uptake of Np-Lev. The technique of obtaining the levan allowed a higher yield than the reference methodology, achieving 71.4% more. The novel nanoparticles (Np-Lev) presented spherical shapes, size of 244 ± 2 nm with homogeneous distribution and zeta potential of −12 ± 1 mV. Characterization techniques, such as infrared spectroscopy and X-ray diffraction, confirmed the presence of levan in the nanoparticles. The thermogravimetric analysis results showed greater thermal resistance when compared to free levan. In addition, Np-Lev were more cytotoxic than levan in both cell lines. This toxicity may be related to the internalization of nanoparticles inside the cells since Np-Lev were captured by the cells, which could increase the activity of levan cytotoxicity. Thus, it was verified a substantial increase in levan yield, also that the levan produced could be used to prepare PIBCA nanoparticles, and finally these Np-Lev showed antiproliferative activity against breast cancer and melanoma cell lines. The results exposed here are of interest to explore levan potential, in addition to nanotechnology, as a promising nanosystem with various biological applications. Further studies are needed to understand the biological behavior of nanoparticles and assess their stability for future therapeutic application.

Does Oncocalyxone A (oncoA) have intrinsic fluorescence?

BackgroundOncocalyxone A (oncoA) is a quinone extracted from the Cordia oncocalyx plant. This compound has pharmacological properties, such as anti-inflammatory, analgesic, and cytotoxic activities, among others. OncoA presents a similar chemical structure to doxorubicin, a drug used in cancer treatment, which possesses an intrinsic fluorescence explored in various studies, including those using doxorubicin-loaded nanoparticles. Thus, due to the chemical structural similarity, the question arose whether oncoA could also show autofluorescence. Therefore, this study proposed to characterize the absorption and emission spectral profiles of oncoA and analyze if this compound could be used as a fluorescent probe. MethodsFor this, fucoidan-coated polyisobutylcyanoacrylate (PIBCA) nanoparticles containing oncoA were prepared, and an uptake study was performed using a human metastatic breast cancer cell line (MDA-MB-231 cells). ResultsOncoA presented a maximum emission wavelength in the blue region, near 430 nm, at 350 nm excitation, compatible with standard microscope optics. Fluorescence microscopy analyses showed that oncoA-loaded PIBCA nanoparticles were internalized by MDA-MB-231 cells under incubation times as shorter as 15 min. ConclusionAccording to these findings, oncoA-encapsulated nanoparticles are promising fluorescent probes and could be useful for cellular uptake studies.

Immune response to antituberculosis drug-loaded gelatin and polyisobutyl-cyanoacrylate nanoparticles in macrophages.

Secondary toxicity of nanoparticles (NPs) in macrophages is a well-known phenomenon. The aim of the study was to investigate the immuneresponse of macrophages after NP treatment. Antituberculosis drugs moxifloxacin and rifampicin were loaded into gelatin and polyisobutyl-cyanoacrylate NPs. The NPs were physicochemical characterized. Cellular immuneresponses and cellular viability were determined. The drug release kinetics vary depending on the type of NP, size and loading capacity. IC50 values of polyisobutyl-cyanoacrylate NPs were lower than for gelatin NPs. NPs treatment induced higher release of Th1 type cytokines compared with free drug. NPs together with chemotherapeutic drugs might be able to trigger an immune response in macrophages. The combined effect might be able to overcome mycobacteria infections.

Unloaded polyisobutylcyanoacrylate nanoparticles: efficiency against bloodstream trypanosomes.

The potential use of polyisobutylcyanoacrylate nanoparticles in antiparasitic chemotherapy is described. The nanoparticles on their own proved to have trypanocidal activity against Trypanosoma brucei brucei in-vitro but not against Trichomonas vaginalis or Entamoeba histolytica. The trypanocidal activity was partly confirmed in-vivo with T. brucei-infected mice.

In vivo performance of parenteral theophylline-loaded polyisobutylcyanoacrylate nanoparticles in rats

Theophylline-loaded polyisobutylcyanoacrylate (PICA) nanoparticles were prepared by emulsifier-free polymerization in aqueous media at ambient conditions. PICA nanoparticles were shown (in vitro) to be a promising controlled delivery system for theophylline. Therefore, this study was conducted to investigate the feasibility of PICA nanoparticles as a parenteral controlled drug delivery system in rats. Wistar rats were given intraperitoneal (i.p.) injections of theophylline solution (4 mg/kg) and theophylline nanospheres suspension (8 mg/kg) on two different occasions. Theophylline serum concentrations were measured by an HPLC assay. The drug solution was rapidly absorbed, distributed, and eliminated. The peak concentration ( C max), 5.34±1.9 mg/l, was achieved 20 min following administration. The mean residence time was 2.94 h, and the apparent clearance was 0.31 (l/h)/kg. After nanospheres administration the mean C max, 2.53±1.1 mg/l, was attained at 3 h. The drug was successfully maintained around this elevated serum drug concentration up to 11 h in rats. The drug concentration was only reduced to 1.43±0.98 mg/l (i.e. reduced by 43.5%) after 20 h of administration. This present study provides evidence that the sorption of theophylline to PICA nanoparticles could control the drug release in rats.

Effect of polyisobutylcyanoacrylate nanoparticles and Lipofectin® loaded with oligonucleotides on cell viability and PKCα neosynthesis in HepG2 cells

The aim of the present study was to evaluate the inhibitory effect on protein kinase Ca (PKCα) neosynthesis of antisense oligonucleotides delivered by two types of carriers. First, PKCα antisense oligonucleotides were associated with polyisobutylcyanoacrylate (PIBCA) nanoparticles pre-coated with cetyltrimethyl ammonium bromide (CTAB), a hydrophobic cation. Adsorption of oligonucleotides onto PIBCA nanoparticles was shown to be a saturating process. From these studies, it was possible to identify two types of particles: positively and negatively charged. Secondly, Lipofectin® was used as another carrier system. These systems were incubated with HepG2 cells. Toxicity was evaluated by the MTT assay, and PKCα neosynthesis was determined by Western blots in conditions where nanoparticles and Lipofectin® were not inducing cytotoxicity. It was observed that both mismatch and antisense oligonucleotides induced an inhibition of PKCa neosynthesis when loaded onto cationic or anionic nanoparticles as well as when complexed to cationic liposomes (Lipofectin®). This non-specific effect was only observed in the phase of PKCα neosynthesis when the cells were first depleted in PKCa by phorbol 12-myristate β-acetate (12-PMA) and in the absence of serum. These results strongly suggest that delivery systems, PIBCA nanoparticles or Lipofectin®, containing a positively charged component (CTAB or cationic lipids), are able to induce a perturbation in the intracellular metabolic activity. In conclusion, it was shown that the commonly used strategy of oligonucleotides targeting with cationic non-viral vectors may display non-specific effects which can lead to artifactual results.

Ciprofloxacin-loaded polyisobutylcyanoacrylate nanoparticles: pharmacokinetics and in vitro antimicrobial activity

The disposition of ciprofloxacin in free form and loaded PIBCA/NP has been studied after intravenous infusion to the rabbit. Data from plasma concentration profiles revealed that pharmacokinetic parameters of ciprofloxacin associated with the colloidal carrier were greatly modified. Thus, ciprofloxacin-loaded PIBCA/NP led to increased AUC, t 1/2 and V d, and to a decreased Cl as compared with drug in solution. This could be due not only to the colloidal drug carrier but also to the pharmacokinetics of ciprofloxacin itself. Studies of efficacy against Mycobacterium avium complex in human macrophages proved that ciprofloxacin-loaded PIBCA/NP was more effective than free drug. The cytotoxicity of the polymeric material was observed at concentrations higher than 80 μg of PIBCA per ml with drastic reduction of viable macrophages. This may explain why the efficacy of ciprofloxacin associated with nanoparticles was much lower than expected.

Polyisobutylcyanoacrylate nanoparticles as drug carriers: influence of sulfur dioxide on the physico-chemical characteristics of ciprofloxacin- and doxorubicin-loaded nanoparticles

The amount of sulfur dioxide present in isobutylcyanoacrylate monomer was examined for the entrapment of ciprofloxacin and doxorubicin into poly(isobutylcyanoacrylate) nanoparticles obtained by emulsion polymerization. In fact, SO 2, commonly used as a polymerization inhibitor, was shown to be a crucial factor modulating the polymerization process. In this report, its optimal concentration to have reproducible preparations regarding size and highest association extent was about 0.5% for both drugs.

Preparation and pharmacological evaluation of physostigmine-loaded polyisobutylcyanoacrylate nanoparticles in rats.

The nanoparticles of physostigmine were prepared by an emulsion polymerization of polyisobutylcyanoacrylate. The drug content, release and particle size distribution of the nanoparticles were characterized. In vitro drug release profiles displayed a retardation by the nanoparticles in comparison to the aqueous solution. Pharmacological evaluation of physostigmine nanoparticles in vivo were carried out with Sprague-Dawley rats. The endogenous acetylcholine was sampled by on-line microdialysis and determined by a sensitive microbore HPLC/ED system in the striatum of rats. The choline oxidase and catalase immobilized enzyme reactors were used as the pre-column to erase choline. Accordingly, this chromatographic flow sequence could be utilized for the quantitative assay of acetylcholine without interference. The results indicate that the increase of acetylcholine (%) in the rats striatum by the nanoparticle was 2.3 times (AUC) higher than that of aqueous solution.

Ciproflexacin-loaded polyisobutylcyanoacrylate nanoparticles: Preparation and characterization

Experimental conditions for attachment of ciprofloxacin hydrochloride to poly(isobutylcyanoacrylate) (PIBCA) nanoparticles (NP) and release of drug were studied. Attachment of the drug was performed by the incorporative and adsorptive processes. The pH, and to a lesser degree the drug concentration in the reaction medium, were shown to be important factors in controlling the size of NP only in the incorporative process. The diameter of NP increased when the initial drug concentration was higher than 1.2 mg/ml. Ciproflaxacin content of NP was influenced by the drug concentration in the polymerization and incubation media. The binding capacity in the adsorptive process was not influenced by the pH. In contrast, the entrapment of ciprofloxacin in the NP by incorporation was greatly influenced by the pH in the range 1.5-4. Thin layer chromatography (TLC) of NP prepared by incorporation showed new products suggesting interactions between ciprofloxacin and isobutylcyanoacrylate. Ciprofloxacin release from nanoparticles prepared by the incorporating process was found to be slower as compared to nanoparticles produced by adsorptive process from which the drug release was practically complete within 1 h in absence of esterases in the release medium. Drug release from the two types of NP was accelerated in the presence of esterases in the release medium.

Complement consumption by poly(ethylene glycol) in different conformations chemically coupled to poly(isobutyl 2-cyanoacrylate) nanoparticles

There is an increasing interest to develop injectable drug polymeric carriers not recognizable by the body as foreign particles and eliminated very quickly from the bloodstream. A polyethylene glycol (PEG)-coating onto injectable particles showed to reduce either protein adsorption and complement consumption, as a function of the PEG density. In this work we compared the complement rejecting ability of PEG in different conformations coupled to polyisobutylcyanoacrylate (PIBCA) nanoparticles, through the analysis of the residual hemolytic capacity of the human serum after contact with the particles. Nanoparticles were formed by chemical coupling of PEG during emulsion/polymerization of isobutylcyanoacrylate (IBCA). Nanoparticles characterization included an investigation of their surface properties, such as hydrophilicity and conformational mobility of the PEG chains grafted on the nanoparticles surface, and PEG total content. The polymerization kinetics of IBCA in presence of PEG or MePEG were also studied. Complement consumption was observed to be very sensitive to the number of particles in contact with human serum, as well as to the PEG conformation, suggesting PEG configuration could affect the particle exposed surface.

Enzyme-loaded PIBCA nanoparticles (SOD and l-ASNase): Optimization and characterization

Some parameters of the emulsion polymerization process were studied in order to optimize the incorporation of the enzymes l-asparaginase ( l-ASNase) and superoxide dismutase (SOD) into polyisobutylcyanoacrylate (PIBCA) nanoparticles and to make a contribution to the characterization of enzyme-loaded nanoparticles. Optimization criteria were the maximization of enzyme load and the minimization of the lost of catalytic activity. The effect of enzyme molecular weight, enzyme concentration and enzyme substrate on the loading performances were studied and discussed considering the mechanism of emulsion polymerization. The effect of the polymerization process on the characteristics of immobilized l-ASNase and SOD, macromolecules with very different three-dimensional structures, were studied. The incorporation of enzymes in PIBCA nanoparticles must be strongly dependent on the enzyme structure. The performances of the incorporation of SOD in PIBCA nanoparticles can be compared with results regarding other colloidal carriers.

Stability of orosomucoid-coated polyisobutylcyanoacrylate nanoparticles in the presence of serum

Orosomucoid-coated polyisobutylcyanoacrylate nanoparticles are proposed as a biomimetic drug carrier. The stability of the orosomucoid layer adsorbed on the nanoparticle surface was evaluated in vitro in the presence of serum. Orosomucoid was determined by micellar electrokinetic capillary chromatography. Results showed that, in the presence of a concentrated fetal calf serum solution, the orosomucoid layer started to desorb after 5 min and that, after 30 min, only 25% of the initial adsorbed orosomucoid layer remained onto the nanoparticle surface. Using turbidimetry and photon correlation spectrometry, it was demonstrated that nanoparticle degradation was mainly responsible for the desorption of orosomucoid. With diluted human serum, orosomucoid desorption was reduced, which allowed the study of the effect of the orosomucoid layer on serum protein adsorption. By comparing the electropherograms of the proteins desorbed from orosomucoid-coated and uncoated nanoparticles, it was observed that orosomucoid could dramatically reduce the adsorption of serum protein onto the nanoparticles. An attempt to identify the main serum proteins adsorbed was also performed: haptoglobin and opsonins (immunoglobulin and C3 protein of complement) adsorbed onto uncoated nanoparticles, whereas only opsonins adsorbed to a lower extent onto orosomucoid-coated nanoparticles. Other unidentified proteins were also adsorbed.

Polyisobutylcyanoacrylate nanoparticles as sustained release system for calcitonin

The potential of nanoparticles of polyisobutylcyanoacrylate as sustained release for peptide was assessed using calcitonin as a model drug. Calcitonin-loaded nanoparticles were obtained following the addition of the peptide before or after polymerization of isobutylcyanoacrylate (CT-NP and CT/NP, respectively). For both formulations, the percentage of binding of calcitonin to the nanoparticles was more than 95% and the particles had an average size of 150 nm. In vitro studies indicate that the release of calcitonin from CT/NP in saline solution containing esterases resulted from the bioerosion of the polymer. However the peptide was not released from CT-NP in this medium. SDS-PAGE electrophoresis and HPLC also showed that calcitonin is tightly bound to the nanoparticles in the CT-NP formulation, very likely by a covalent binding. After intravenous injection in rats, free calcitonin, CT/NP and CT-NP had the same hypocalcemic activity (at the same dose). Following a subcutaneous injection in rats, the two encapsulated forms of calcitonin showed a more important and more prolonged hypocalcemic effect than free calcitonin. 1 h after injection, calcitonin level was lower after CT-NP injection than CT/NP or free calcitonin injection. However, calcitonin level was sustained for more than 24 h after CT-NP injection.

In Vitro Evaluation of Polyisobutylcyanoacrylate Nanoparticles as a Controlled Drug Carrier for Theophylline

AbstractTheophylline nanoparticles were prepared by emulsifier-free emulsion polymerization technique in continuos aqueous phase. The polymerization process was carried out at a pH 3. Different concentrations of isobutylcyacoacrylate (IBCA) were used to investigate the effect of monomer concentration. The in vitro release of theophylline in phosphate buffer was studied. An HPLC assay was used to follow the release of the drug from the nanospheres. This polymerization technique was able to hold 2349% of the drug initially dissolved in the aqueous medium. The percentage drug loading is a monomer concentration dependent. Increasing the monomer concentration above 40 μL per mL resulted in a less significant increase in the percentage drug loading. The percentage of drug retained in nanospheres up to 24 hr followed first order kinetics (r = 0.94-0.98). The release rate constant of theophylline from nanoparticles is inversely related to the monomer concentration in the initial solution (r = 0.996). In the mean ...

Adsorption of Allergen Extracts onto Colloidal Particles

The adsorption of different allergen extracts onto colloidal particles (nanoparticles and nanocapsules) made of polyisobutylcyanoacrylate (PIBCA) and polymethacrylate copolymer has been studied. A qualitative analysis of the adsorption has been performed using both sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting technique. These studies have shown that the adsorption onto PIBCA nanoparticles was not specific to certain types of proteins but that all kinds of proteins were adsorbed. The stability of the adsorption of a Dactylis glomerata extract onto PIBCA nanoparticles was studied in the presence of human serum. A slight desorption of D. glomerata allergens was observed only in the presence of a high concentration of serum in the incubation medium. The desorption observed under these conditions was the consequence of both the biodegradation of the polymer by serum esterases and the competitive displacement of allergens by serum proteins. The influence of the surfactant (Pluronic F 68) or of the stabilizer (Dextran 70) used in preparing colloidal particles was also investigated.

P23 Polyisobutylcyanoacrylate nanoparticles as sustained release system for calcitonin

P23 Polyisobutylcyanoacrylate nanoparticles as sustained release system for calcitonin

Capillary electrophoresis monitoring of the competitive adsorption of albumin onto the orosomucoid-coated polyisobutylcyanoacrylate nanoparticles.

The simultaneous and rapid quantitation of a glycoprotein, human orosomucoid, and a protein, human serum albumin (HSA), by micellar electrokinetic capillary electrophoresis was developed and optimized (pH and sodium dodecyl sulfate concentration) in order to study the competitive adsorption of HSA onto orosomucoid-coated nanoparticles of polyisobutylcyanoacrylate. This method provided satisfactory repeatability and the response was linear for concentrations of orosomucoid and HSA ranging from 0.025 to 0.500 mg/mL (r > 0.994 for both proteins). To study the competitive adsorption of HSA, the amounts of free orosomucoid and free HSA were determined in the supernatant obtained after centrifugation of the orosomucoid-coated nanoparticle suspension incubated with HSA. Furthermore, the quantities of both orosomucoid and HSA absorbed onto nanoparticles were also determined after desorption of these molecules from the nanoparticle surface, using sodium dodecyl sulfate. No analytical interference was observed with this surfactant. The results showed that HSA did not at all absorb onto the orosomucoid-coated nanoparticles and, thus, that this protein did not displace the layer of absorbed orosomucoid from the nanoparticle surface.

An interpretative analysis of the effect of the surfactants used for the preparation of polyalkylcyanoacrylate nanoparticles on the release process.

The release of fluorescein from polyethylcyanoacrylate (PECA) or polyisobutylcyanoacrylate (PICA) nanoparticles was affected by the surfactants used for the preparation. The different surfactants also modified the molecular weight, size and loading of the nanoparticles. However, these factors were not be responsible for the different release. According to the release profiles and the Baker-Lonsdale model, a portion of fluorescein was concentrated near the nanoparticle surface. Thus, a non-homogeneous distribution of the fluorescent probe inside the nanoparticles was hypothesized. This distribution could reflect the fluorescein position inside the micella during the polymerization stage, or could be reached during the washing stage as the consequence of a different effect of the surfactants on the porosity of the nanoparticle structure.

Adsorption of beta-blockers onto polyisobutylcyanoacrylate nanoparticles measured by depletion and dielectric methods.

Adsorption of beta-blockers onto polyisobutylcyanoacrylate nanoparticles measured by depletion and dielectric methods.