Polybutylcyanoacrylate Nanoparticles Research Articles

A new agent for contrast-enhanced intravascular ultrasound imaging in vitro: polybutylcyanoacrylate nanoparticles with drug-carrying capacity

This study prepared and evaluated polymeric polybutylcyanoacrylate (PBCA) nanoparticles (NPs) that can be used as a new agent for contrast-enhanced intravascular ultrasound (IVUS) imaging with drug delivery capacity. The nanoformulation was successfully developed using suspension polymerisation and characterised in terms of size, size distribution, zeta potential, morphology, stability, toxicity effects, imaging effects and drug release study. The results showed that the nanoparticles were round and hollow, with a particle diameter of 215.8 ± 25.3 nm and a zeta potential of −22.2 ± 4.1 mV. In vitro experiments, the nanoparticles were safe, non-toxic, and stable in nature with the capacity to carry and release drug (ant-miR-126). Moreover, the nanoparticles can match the high-frequency probe of commercially IVUS as a contrast agent to improve the resolution of imaging (the mean echo intensity ratio in the vascular wall increased significantly from 10.89 ± 1.10 at baseline, to 24.51 ± 1.91 during injection and 43.70 ± 0.88 after injection, respectively p < .0001). Overall, a new nano agent with drug-carrying capacity was prepared, which can be used in combination with IVUS for simultaneous diagnosis and targeted therapy of coronary atherosclerosis.

Blood-Nanoparticle Interactions Create a Brain Delivery Superhighway for Doxorubicin.

This study investigated the brain targeting mechanism of doxorubicin-loaded polybutyl cyanoacrylate (PBCA) nanoparticles, particularly their interactions with the blood-brain barrier (BBB). The BBB protects the brain from drugs in the bloodstream and represents a crucial obstacle in the treatment of brain cancer. An advanced computer model analyzed the brain delivery of two distinct formulations, Doxil® and surfactant-coated PBCA nanoparticles. Computational learning was combined with in vitro release and cell interaction studies to comprehend the underlying brain delivery pathways. Our analysis yielded a surprising discovery regarding the brain delivery mechanism of PBCA nanoparticles. While Doxil® exhibited the expected behavior, accumulating in the brain through extravasation in tumor tissue, PBCA nanoparticles employed a unique and previously uncharacterized mechanism. They underwent cell hitchhiking, resulting in a remarkable more than 1000-fold increase in brain permeation rate compared to Doxil® (2.59 × 10-4 vs 0.32 h-1). The nonspecific binding to blood cells facilitated and intensified interactions of surfactant-coated PBCA nanoparticles with the vascular endothelium, leading to enhanced transcytosis. Consequently, the significant increase in circulation time in the bloodstream, coupled with improved receptor interactions, contributes to this remarkable uptake of doxorubicin into the brain.

Investigating the Properties and Cytotoxicity of Cisplatin-Loaded Nano-Polybutylcyanoacrylate on Breast Cancer Cells

Background: This study aimed to develop a novel drug formulation using polybutylcyanoacrylate (PBCA) nanoparticles to deliver cisplatin, a commonly used chemotherapeutic agent for breast cancer treatment.Materials and Methods: PBCA nanoparticles were synthesized using a mini-emulsion polymerization method, and the resulting NPs were comprehensively characterized for their physical properties, such as size, size distribution, zeta potential, drug loading, and encapsulation efficiency. In addition, the cytotoxicity of the NPs was assessed, along with their ability to release the entrapped drugs over time. Results: The results showed that the PBCA nanoparticles had a mean size of 457 ± 7.4 nm, a size distribution of 0.253±0.011 and a negative zeta potential of -12.3 ± 1.3 mV. The drug encapsulation efficiency and loading capacity of cisplatin-PBCA were found to be 45.6 ± 2.7% and 3.5 ±0.8%, respectively; The release of the drug from the PBCA was estimated to be approximately 12.2±1.1% after 45 hours. The cytotoxic effects of the nanoparticle formulation were significantly enhanced compared to the free drug. The cytotoxicity of cisplatin-PBCA was evaluated in the T-47D breast cancer cell line, showing promising results as a potential drug formulation for breast cancer therapy. Conclusions: These findings suggest that cisplatin-PBCA may offer advantages over traditional cisplatin formulations, potentially improving the efficacy and reducing the toxicity of breast cancer treatment.

Design, Preparation, and Evaluation of Osthol Poly-Butyl-Cyanoacrylate Nanoparticles with Improved In Vitro Anticancer Activity in Neuroblastoma Treatment.

Osthol (osthole), known as a neuroprotective drug, has shown potent anticancer activity. However, the potential clinical application of osthol is limited due to its low water solubility and low bioavailability. Polybutyl cyanoacrylate (PBCA) has been widely used to improve the solubility of drugs with poor water solubility. In this study, an orthogonal experimental design (OED) was applied to design the preparation process of PBCA nanoparticles (NPs). Then, nanoparticles were prepared and evaluated in terms of physicochemical properties, in vitro release, and cellular uptake, etc. Further, the anti-cancer activity of osthol-PBCA NPs was demonstrated in SH-SY5Y cells. The pharmacokinetics and area under the curve (AUC) were investigated. The obtained osthol-NPs presented a spherical shape with a particle size of 110 ± 6.7 nm, a polydispersity index (PDI) of 0.126, and a zeta potential of −13 ± 0.32 mV. Compared with the free osthol, the drugs in osthol-NPs presented better stability and sustained release pattern activity. In vitro analysis using SH-SY5Y neuroblastoma cells showed that osthol-loaded nanoparticles displayed a significantly enhanced intracellular absorption process (three times) and cytotoxicity compared with free osthol (p < 0.05, increased 10–20%). The in vivo pharmacokinetic study revealed that the AUC of osthol-NPs was 3.3-fold higher than that of free osthol. In conclusion, osthol-PBCA NPs can enhance the bioactivity of osthol, being proposed as a novel, promising vehicle for drug delivery.

Comparative study on the antitumor effects of gemcitabine polybutylcyanoacrylate nanoparticles coupled with anti-human MUC1 and CA199 monoclonal antibodies on pancreatic cancer in vitro and in vivo

Background and Study AimsThis study was designed to compare the antitumor effects of anti-human MUC1 monoclonal antibody with those of anti-human CA199 monoclonal antibody coupled with drug-loaded polybutylcyanoacrylate nanoparticles on human pancreatic cancer cell lines and pancreatic cancer-bearing model animals and to screen more efficient targeting molecules. Patients and MethodsGemcitabine-loaded nanospheres were prepared by emulsion polymerization (GEM-PBCA-NP), and then, anti-MUC1 monoclonal antibody was coupled with GEM-PBCA-NP (MUC1-GEM-PBCA-NP), and anti-human CA199 monoclonal antibody was coupled with GEM-PBCA-NP (CA199-GEM-PBCA-NP), using the chemical crosslinking method. The cell-killing rates were detected using MTT assay. The changes in the tumor cell cycle and apoptosis after treatment were detected using flow cytometry. Then, the subcutaneous planting method was adopted to establish an animal model of pancreatic cancer: two nanometer microspheres were injected into the body of nude mice via the tail vein; the tumor suppression effect was detected after treatment; then, the groups were compared. ResultsIn vitro, the cell-killing rate of each experimental group was significantly different from that of the control group (P < 05). The MUC1-GEM-PBCA-NP group had a significantly higher cell-killing rate than the other groups (P < 05). The apoptosis rate of the MUC1-GEM-PBCA-NP treatment group was significantly higher than that of other groups (P < 05). In vivo, the tumor inhibition rate of the MUC1-GEM-PBCA-NP treatment group was 72.69% ± 4.29%, which was significantly higher than those of other groups (P < 0.05). The tumor inhibition rate of the CA199-GEM-PBCA-NP treatment group was 56.58% ± 5.11%, which was significantly higher than those of other control groups (P < 0.05). At the end of treatment, the average tumor mass of the MUC1-GEM-PBCA-NP treatment group was 433.55 ± 12.49 mg, which was significantly lower than those of other groups (P < 0.05). ConclusionCompared with CA199-GEM-PBCA-NP, MUC1-GEM-PBCA-NP is more effective in vitro and in vivo. MUC1 could be a target molecule in treating pancreatic cancer.

An Ultrasound-Responsive Theranostic Cyclodextrin-Loaded Nanoparticle for Multimodal Imaging and Therapy for Atherosclerosis.

Atherosclerosis is a major cause of mortality and morbidity worldwide. Left undiagnosed and untreated, atherosclerotic plaques can rupture and cause cardiovascular complications such as myocardial infarction and stroke. Atherosclerotic plaques are composed of lipids, including oxidized low-density lipoproteins and cholesterol crystals, and immune cells, including macrophages. 2-Hydroxypropyl-beta-cyclodextrin (CD) is FDA-approved for capturing, solubilizing, and delivering lipophilic drugs in humans. It is also known to dissolve cholesterol crystals and decrease atherosclerotic plaque size. However, its low retention time necessitates high dosages for successful therapy. This study reports CD delivery via air-trapped polybutylcyanoacrylate nanoparticles (with diameters of 388±34nm) loaded with CD (CDNPs). The multimodal contrast ability of these nanoparticles after being loaded with IR780 dye in mice is demonstrated using ultrasound and near-infrared imaging. It is shown that CDNPs enhance the cellular uptake of CD in murine cells. In an ApoE-/- mouse model of atherosclerosis, treatment with CDNPs significantly improves the anti-atherosclerotic efficacy of CD. Ultrasound triggering further improves CD uptake, highlighting that CDNPs can be used for ultrasound imaging and ultrasound-responsive CD delivery. Thus, CDNPs represent a theranostic nanocarrier for potential application in patients with atherosclerosis.

A study on the antitumor effect of gemcitabine polybutylcy- anoacrylate nanoparticles coupled with Mucin 1 monoclonal antibody on pancreatic cancer in vitro and in vivo.

Previous studies have discovered a high expression rate of Mucin 1 (MUC1) in pancreatic cancer tissue, and its abnormal glycosylation causes MUC1 to expose new protein epitopes or glycoantigens. To investigate the therapeutic effect of drug-loaded gemcitabine polybutylcyanoacrylate nanoparticles coupled with anti-human MUC1 monoclonal antibody (mAb) on human pancreatic cancer cell line and xenografts. Randomized controlled trial. Gemcitabine-loaded nanospheres were prepared by emulsion polymerization; then, the anti-MUC1 mAb coupled with gemcitabine polybutylcyanoacrylate nanoparticles (MUC1-GEM-PBCA-NP) was prepared by chemical cross-linking. Cell-killing rates were detected by MTT assay in in vitro study, and changes in tumor cell cycle and apoptosis after treatment were detected by flow cytometry. Furthermore, in in vivo study, MUC1-GEM-PBCA-NP was injected into nude mice through the tail vein. Gemcitabine-loaded polybutylcyanoacrylate nanoparticles (GEM-PBCA-NP), gemcitabine bulk drug and empty nanoparticles (PBCA-NP), and normal saline blank control groups were established. Finally, data obtained were compared between groups. Compared with the control group, the cell-killing rate of each experimental group was significantly different (P < 0.05) in in vitro study, among which the MUC1-GEM-PBCA-NP group was significantly higher than other groups (P < 0.05). In addition, the apoptosis rate of the MUC1-GEM-PBCA-NP treatment group was significantly higher than that of other groups (P < 0.05). Furthermore, in in vivo study, the tumor inhibition rate of the MUC1-GEM-PBCA-NP treatment group was (68.14% ±1.66%), which was significantly higher than other control groups (P < 0.05). Finally, at the end of the treatment, the average tumor mass of the MUC1-GEM-PBCA-NP treatment group was (471.61 mg ± 12.16 mg), which was significantly lower than those of other control groups (P < 0.05). MUC1-GEM-PBCA-NP could have an excellent inhibitory effect on tumors; thus, requiring further study.

Double-Coated Poly(butyl Cyanoacrylate) Nanoparticles as a Potential Carrier for Overcoming P-Gp- and BCRP-Mediated Multidrug Resistance in Cancer Cells

The present study evaluates poly (butyl cyanoacrylate) nanoparticles (PBCA-NPs), double-coated with Tween 80 and polyethylene glycol (PEG) 20,000 as a potential carrier system for overcoming P-glycoprotein (P-gp) and breast cancer resistant protein (BCRP)-mediated multidrug resistance (MDR) in cancer cell lines. Doxorubicin-loaded PBCA-NPs were prepared by the anionic polymerization method and were successively double-coated with Tween 80 and PEG 20000 at varied concentrations. MDR reversing potential was investigated by cellular uptake in P-gp overexpressing cell line. And, the outcomes were verified by modified MTT assay in P-gp or BCRP overexpressing cell lines. The findings from the cell uptake study indicate that double-coated PBCA-NPs significantly enhanced doxorubicin accumulation within the cells. MTT assays revealed that double-coated PBCA-NPs significantly potentiated the sensitivity of doxorubicin in P-gp overexpressing cells, in comparison to free doxorubicin, single-, and un-coated PBCA-NPs, respectively. Moreover, further increase in concentration with Tween 80, double-coated PBCA-NPs significantly enhanced the sensitivity of doxorubicin in BCRP overexpressing cell line, in comparison to single- and double-coated formulations (with lower concentration of Tween 80). Hence, it could be concluded that double-coated PBCA-NPs can be used as a potential carrier for enhancing doxorubicin accumulation in MDR cancer cells.

Characterization and Optimization of Chitosan-Coated Polybutylcyanoacrylate Nanoparticles for the Transfection-Guided Neural Differentiation of Mouse Induced Pluripotent Stem Cells.

Gene transfection is a valuable tool for analyzing gene regulation and function, and providing an avenue for the genetic engineering of cells for therapeutic purposes. Though efficient, the potential concerns over viral vectors for gene transfection has led to research in non-viral alternatives. Cationic polyplexes such as those synthesized from chitosan offer distinct advantages such as enhanced polyplex stability, cellular uptake, endo-lysosomal escape, and release, but are limited by the poor solubility and viscosity of chitosan. In this study, the easily synthesized biocompatible and biodegradable polymeric polysorbate 80 polybutylcyanoacrylate nanoparticles (PS80 PBCA NP) are utilized as the backbone for surface modification with chitosan, in order to address the synthetic issues faced when using chitosan alone as a carrier. Plasmid DNA (pDNA) containing the brain-derived neurotrophic factor (BDNF) gene coupled to a hypoxia-responsive element and the cytomegalovirus promotor gene was selected as the genetic cargo for the in vitro transfection-guided neural-lineage specification of mouse induced pluripotent stem cells (iPSCs), which were assessed by immunofluorescence staining. The chitosan-coated PS80 PBCA NP/BDNF pDNA polyplex measured 163.8 ± 1.8 nm and zeta potential measured −34.8 ± 1.8 mV with 0.01% (w/v) high molecular weight chitosan (HMWC); the pDNA loading efficiency reached 90% at a nanoparticle to pDNA weight ratio of 15, which also corresponded to enhanced polyplex stability on the DNA stability assay. The HMWC-PS80 PBCA NP/BDNF pDNA polyplex was non-toxic to mouse iPSCs for up to 80 μg/mL (weight ratio = 40) and enhanced the expression of BDNF when compared with PS80 PBCA NP/BDNF pDNA polyplex. Evidence for neural-lineage specification of mouse iPSCs was observed by an increased expression of nestin, neurofilament heavy polypeptide, and beta III tubulin, and the effects appeared superior when transfection was performed with the chitosan-coated formulation. This study illustrates the versatility of the PS80 PBCA NP and that surface decoration with chitosan enabled this delivery platform to be used for the transfection-guided differentiation of mouse iPSCs.

The Effect of Polybutylcyanoacrylate Nanoparticles as a Protos Delivery Vehicle on Dental Bone Formation.

Background: Dental implants are commonly used for missing teeth, for which success depends heavily on the quality of the alveolar bone. The creation of an ideal implant site is a key component in shortening the treatment time, which remains clinically challenging. Strontium ranelate (Protos) is an anti-osteoporotic agent which has previously been used to promote bone formation, however the systemic use of Protos has been linked to serious cardiovascular and venous thromboembolic events, thus local delivery strategies may be better suited for this purpose. In this study, a biodegradable, and biocompatible nanocarrier “polybutylcyanoacrylate” (PBCA) loaded with strontium was constructed and its ability to promote bone formation was assessed. Methodology: PBCA nanoparticles loaded with strontium (PBCA-Sr NPs) were synthesized using the emulsion polymerization method, and their physical properties (zeta potential, size and shape) and entrapment efficiency were characterized. Committed MSCs (osteoblasts) were derived from the differentiation of cultured rat mesenchymal stem cells (MSC), which were tested with the PBCA-Sr NPs for cytotoxicity, inflammatory response, bone formation and mineralization. Scanning electron microscopy was performed following a 7-day treatment of PBCA-Sr NPs on decellularized procaine mandibular bone blocks grafted with osteoblasts. Results: Spherical PBCA-Sr NPs of 166.7 ± 2.3 nm, zeta potential of −1.15 ± 0.28 mV with a strontium loading efficiency of 90.04 ± 3.27% were constructed. The presence of strontium was confirmed by energy-dispersive X-ray spectroscopy. Rat committed MSCs incubated in PBCA-Sr NPs for 24 hrs showed viabilities in excess of 90% for concentrations of up to 250 ug/mL, the cellular expression of osteocalcin and alkaline phosphatase were 1.4 and 1.3 times higher than the untreated control, and significantly higher than those treated with strontium alone. Bone formation was evident following osteoblast engraftment on the decellularized procaine mandibular bone block with PBCA-Sr NPs, which appeared superior to those treated with strontium alone. Conclusion: Treatment of committed MSCs with PBCA-Sr NPs showed higher expression of markers of bone formation when compared with strontium alone and which corresponded to greater degree of bone formation observed on the 3-dimensinal decellularized procaine mandibular bone block. Further quantitative analysis on the extent of new bone formation is warranted.

Gene therapy with caspase-3 small interfering RNA-nanoparticles is neuroprotective after optic nerve damage.

Apoptosis, a key mechanism of programmed cell death, is triggered by caspase-3 protein and lowering its levels with gene therapy may rescue cell death after central nervous system damage. We developed a novel, non-viral gene therapy to block caspase-3 gene expression using small interfering RNA (siRNA) delivered by polybutylcyanoacrylate nanoparticles (CaspNPs). In vitro CaspNPs significantly blocked caspase-3 protein expression in C6 cells, and when injected intraocularly in vivo, CaspNPs lowered retinal capsase-3 immunofluorescence by 57.9% in rats with optic nerve crush. Longitudinal, repeated retinal ganglion cell counts using confocal neuroimaging showed that post-traumatic cell loss after intraocular CaspNPs injection was only 36.1% versus 63.4% in lesioned controls. Because non-viral gene therapy with siRNA-nanoparticles can selectively silence caspace-3 gene expression and block apoptosis in post-mitotic neurons, siRNA delivery with nanoparticles may be promising for neuroprotection or restoration of central visual system damage and other neurological disorders. The animal study procedures were approved by the German National Act on the use of experimental animals (Ethic Committee Referat Verbraucherschutz, Veterinärangelegenheiten; Landesverwaltungsamt Sachsen-Anhalt, Halle, Germany, # IMP/G/01-1150/12 and # IMP/G/01-1469/17).

Preparation, Characterization, and Evaluation of Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved In Vitro and In Vivo Anticancer Activities.

This study aimed to evaluate the therapeutic efficacy of the cisplatin encapsulated into polybutylcyanoacrylate (PBCA) nanoparticles for the treatment of kidney cancer. The nanoformulation was successfully developed using the miniemulsion polymerization method and characterized in terms of size, size distribution, drug loading and encapsulation efficiencies, drug release behavior, in vitro cytotoxicity effects, in vivo toxicity, and therapeutic effects. Cisplatin-loaded PBCA nanoparticles were confirmed to be in nanoscale with the drug entrapment efficiency of 23% and controlled drug release profile, in which only 9% of the loaded drug was released after 48 h. The nanoparticles caused an increase in the cytotoxicity effects of cisplatin against renal cell adenocarcinoma cells (ACHN) (2.3-fold) and considerably decreased blood urea nitrogen and creatinine concentrations when compared to the standard cisplatin (1.6-fold and 1.5-fold, respectively). The nanoformulation also caused an increase in the therapeutic effects of cisplatin by 1.8-fold, in which a reduction in the mean tumor size was seen (3.5 mm vs. 6.5 mm) when compared to the standard cisplatin receiver rats. Overall, cisplatin-loaded PBCA nanoparticles can be considered as a promising drug candidate for the treatment of kidney cancer due to its potency to reduce the side effects of cisplatin and its toxicity and therapeutic effects on cancer-bearing Wistar rats.

Protective Effect of PBCA Nanoparticles Loaded with Thymulin Against the Relapsing-Remitting Form of Experimental Autoimmune Encephalomyelitis in Mice.

Relapsing–remitting experimental autoimmune encephalomyelitis (rEAE) in mice is a model that closely resembles relapsing–remitting multiple sclerosis in humans. This study aims to investigate a new approach to modulation of the inflammatory response in rEAE mice using a thymic peptide thymulin bound to polybutylcyanoacrylate (PBCA) nanoparticles. PBCA nanoparticles were used to prolong the presence of thymulin in the blood. Cytokine levels in blood were measured by ELISA; NF-κB and SAPK/JNK cascade activation, as well as Hsp72 and p53 protein expression, were measured by Western blotting. Animal health statuses were estimated using severity scores. Results showed that the cytokine response in rEAE was multi-staged: an early phase was accompanied by an increase in plasma interferon-γ, while the interleukin (IL)-17 response was markedly increased at a later stage. The stages were attributed to rEAE induction and maintenance phases. Thymulin significantly alleviated symptoms of rEAE and lowered plasma cytokine levels both in early and later stages of rEAE, and decreased NF-κB and SAPK/JNK cascade activation. Thymulin modulated NF-kappaB pathway activity via site-specific phosphorylation of RelA/p65 protein (at Ser276 and Ser536). The effect of nanoparticle-bound thymulin was more pronounced than the effect of free thymulin. Therefore, PBCA–thymulin can be considered a prospective treatment for this pathology.

How Nanoparticle Physicochemical Parameters Affect Drug Delivery to Cells in the Retina via Systemic Interactions.

Minor changes in the composition of poloxamer 188-modified, DEAE-dextran-stabilized (PDD) polybutylcyanoacrylate (PBCA) nanoparticles (NPs), by altering the physicochemical parameters (such as size or surface charge), can substantially influence their delivery kinetics across the blood-retina barrier (BRB) in vivo. We now investigated the physicochemical mechanisms underlying these different behaviors of NP variations at biological barriers and their influence on the cellular and body distribution. Retinal whole mounts from rats injected in vivo with fluorescent PBCA NPs were processed for retina imaging ex vivo to obtain a detailed distribution of NPs with cellular resolution in retinal tissue. In line with previous in vivo imaging results, NPs with a larger size and medium surface charge accumulated more readily in brain tissue, and they could be more easily detected in retinal ganglion cells (RGCs), demonstrating the potential of these NPs for drug delivery into neurons. The biodistribution of the NPs revealed a higher accumulation of small-sized NPs in peripheral organs, which may reduce the passage of these particles into brain tissue via a "steal effect" mechanism. Thus, systemic interactions significantly determine the potential of NPs to deliver markers or drugs to the central nervous system (CNS). In this way, minor changes of NPs' physicochemical parameters can significantly impact their rate of brain/body biodistribution.

Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved Properties as an Anticancer Agent.

This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs’ properties. The NPs were synthesized using an anionic polymerization method and were characterized in terms of size, drug loading efficiency, drug release profile, cytotoxicity effects, drug efficacy, and drug side effects. In this regard, dynamic light scattering (DLS), scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) methods, and hematoxylin and eosin (H&E) staining were used. The results showed that the size and the drug loading efficiency of the synthesized spherical NPs were 355–386 nm and 14–19%, respectively. Also, the drug release profile showed a controlled and slow drug release pattern with approximately 10% drug release over 48 h. In addition, the NPs significantly increased the cytotoxicity of the cisplatin in vitro environment by approximately 2 times and enhanced the therapeutic effects of the drug in vivo environment by increasing the survival time of lung-cancer-bearing mice by 20% compared to the standard drug receiver group. Also, the nanoformulation decreased the drug toxicity in an in vivo environment. According to the results, increasing the temperature and PEG concentration improved the properties of the drug loading efficiency, drug release profile, and cytotoxicity effect of drug-loaded NPs. Consequently, the synthesized formulation increased the survival of tumor-bearing mice and simultaneously decreased the cisplatin toxicity effects. In conclusion, the prepared nanoformulation can be considered a promising candidate for further evaluation for possible therapeutic use in the treatment of lung cancer.

Research and development of 2-ethyl-6-methyl-3-oxypyridine succinate nano-form for the treatment of epilepsy

The aimis to develop an antiepileptic drug based on polymer nanoparticles with 2-ethyl-6-methyl-3-oxypyridine succinate to facilitate the drug transport through the blood-brain barrier.Materials and methods.The nano-drug was created using the biologically active substance 2-ethyl-6-methyl-3-hydroxypyridine succinate and polybutyl cyanoacrylate (PBCA) nanoparticles. The advantages of this nano-form over the active ingredient of the same drug were studied using experimental models: the maximum electroshock test (MES), the antagonism test with corazol, models with a cobaltinduced epileptic focus and secondary generalized convulsions, and models of status epilepticus.Results.The antiseizure effects of the nanoform on the experimental models of epilepsy are identified.Conclusion.The nano-drug reduces the number of secondary generalized clonic-tonic seizures by 7.8 times; it also reduces 10-fold the animal mortality and diminishes the seizure manifestations that occur in the interictal period of the epileptic status.

Major effects on blood-retina barrier passage by minor alterations in design of polybutylcyanoacrylate nanoparticles

Because the blood-brain barrier (BBB) is an obstacle for drug-delivery, carrier systems such as polybutylcyanoacrylate (PBCA) nanoparticles (NPs) have been studied. Yet, little is known of how physiochemical features such as size, surfactants and surface charge influence BBB passage in vivo. We now used a rat model of in vivo imaging of the retina - which is brain tissue and can reflect the situation at the BBB - to study how size and surface charge determine NPs’ ability to cross the blood-retina barrier (BRB). Interestingly, for poloxamer 188-modified, DEAE-dextran-stabilised, fluorescent PBCA NPs, decreasing the average zeta-size from 272 nm to 172 nm by centrifugation reduced the BRB passage of the NPs substantially. Varying the zeta potential within the narrow range of 0–15 mV by adding different amounts of stabiliser revealed that 0 mV and 15 mV were less desirable than 5 mV which facilitated the BRB passage. Moreover, whether the fluorescent marker was adsorbed or incorporated also influenced the transport into the retina tissue. Thus, minor changes in design of nano-carriers can alter physicochemical parameters such as size or zeta potential, thus substantially influencing NPs’ biological distribution in vivo, possibly by interactions with blood constituents and peripheral organs.

Synthesis and characterization of polyethylene glycols conjugated to polybutylcyanoacrylate nanoparticles

ABSTRACTThis study aimed to evaluate the cytotoxicity effects of various polyethylene glycols (PEGs), and construction and characterization of polybutylcyanoacrylate (PBCA) nanoparticles. Cytotoxicity was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on rat glioma C6 cell line, and PBCA nanoparticles were prepared by emulsion polymerization method. Also, the nanoparticles were characterized by dynamic light scattering and scanning electron microscopy. The findings showed that PEGs were approximately safe and cytotoxicity was inversely proportional with their molecular weights. In addition, the size of nanoparticles were increased with reducing molecular weights of PEGs. PEGs with negligible cytotoxicity and stabilizing functionality were demonstrated in this study.

In vitro effect of imatinib mesylate loaded on polybutylcyanoacrylate nanoparticles on leukemia cell line K562

The study aimed to prepare imatinib mesylate-loaded polybutylcyanoacrylate (PBCA) nanoparticles and evaluate their efficacy on leukemia cell line K562. The formulation was prepared by miniemulsion polymerization technique. Nanoparticles were characterized by dynamic light scattering (DLS), spectrophotometry, Fourier transform infrared spectroscopy (FTIR), dialysis membrane, and 3-(4,5-dimethylthiazol-2-Yl)-2,5-diphenyltetrazolium bromide (MTT) techniques. Nanoscale particles with high encapsulation efficiency (86%) and physical entrapment of drug were observed. In addition, nanoparticles showed suitable drug retention capability and potentiate the cytotoxicity effects of imatinib mesylate. Findings of study suggested PBCA nanoparticles are promising carrier for imatinib mesylate delivery to leukemia cell line K562.

Drug Delivery of Cisplatin to Breast Cancer by Polybutylcyanoacrylate Nanoparticles

AbstractBreast cancer is the most common cancer and the second cause of cancer‐related death in women worldwide. Chemotherapy of disease is impeded by subsequent relapse and metastasis. Nanoparticles as drug carriers have been shown the promising results. Cisplatin‐loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) were successfully constructed, and its efficacy and toxicity were evaluated on an orthotopic breast cancer model. Cisplatin‐loaded PBCA NPs were prepared by miniemulsion polymerization technique. NPs were characterized with photon correlation spectroscopy, inductively coupled plasma optical emission spectrometry (ICP‐OES) and spectrophotometry techniques. MTT assay was used to evaluate the cytotoxicity of nanodrug. To evaluate the efficacy of Cisplatin‐loaded PBCA NPs an orthotopic model of breast tumor was employed. The cell viability of nanodrug compared to that of the standard drug had a significant decrease by 75% at the first 24 h. In vivo studies showed that the number of mice treated with Cisplatin bound to PBCA NPs was significantly more than the standard drug receivers (8 against 5 mice). Considering the body weight loss as toxicity effects, nanodrug receivers were also shown significantly lesser body weight loss compared to drug receivers groups (20 against 26%).