Investigation of antiproliferative efficacy and apoptosis induction in leukemia cancer cells using irinotecan-loaded liposome-embedded nanofibers constructed from chitosan.

Liposomes and nanofibers have been implemented as efficacious vehicles for delivering anticancer drugs. With this view, this study explores the antiproliferative efficacy and apoptosis induction in leukemia cancer cells utilizing irinotecan-loaded liposome-embedded nanofibers fabricated from chitosan, a biological source. Specifically, we investigate the effectiveness of poly(ε-caprolactone) (PCL)/chitosan (CS) (core)/irinotecan (CPT)nanofibers (termed PCL-CS10 CPT), PCL/chitosan/irinotecan (core)/PCL/chitosan (shell) nanofibers (termed CS/CPT/PCL/CS), and irinotecan-coloaded liposome-incorporated PCL/chitosan-chitosan nanofibers (termed CPT@Lipo/CS/PCL/CS) in releasing irinotecan in a controlled manner and treating leukemia cancer. The fabricated formulations were characterized utilizing Fourier transform infrared analysis, transmission electron microscopy, scanning electron microscopy, dynamic light scattering, zeta potential, and polydispersity index. Irinotecan was released in a controlled manner from nanofibers filled with liposomes over 30 days. The cell viability of the fabricated nanofibrous materials toward Human umbilical vein endothelial cells (HUVECs) non-cancerous cells after 168 h was >98 % ±â€¯1 %. The CPT@Lipo/CS/PCL/CS nanofibers achieved maximal cytotoxicity of 85 % ±â€¯2.5 % against K562 leukemia cancer cells. The CPT@Lipo/CS/PCL/CS NFs exhibit a three-stage drug release pattern and demonstrate significant in vitro cytotoxicity. These findings indicate the potential of these liposome-incorporated core-shell nanofibers for future cancer therapy.

Immunomodulatory effect of Myrtenol on benzo (a) pyrene-induced lung cancer in Swiss albino mice via modulation of tumor markers, cytokines and inhibition of PCNA expression.

Lung cancer is one of the most common cancers in men. Although many diagnostic and treatment regimens have been followed in the treatment for lung cancer, increasing mortality rate due to lung cancer is depressing and hence requires alternative plant based therapeutics with with less side-effects. Myrtenol exhibits anti-inflammatory and antioxidant properties. Hence we intended to study the effect of Myrtenol on B(a)P-induced lung cancer. Our study showed that B(a)P lowered hematological count, decreased phagocyte and avidity indices, nitroblue tetrazolium (NBT) reduction, levels of immunoglubulins, antioxidant levels, whereas Myrtenol treatment restored them back to normal levels. On the other hand, xenobiotic and liver dysfunction marker enzymes and pro-inflammatory cytokines were elevated on B(a)P exposure, which retuned back to normal by Myrtenol. This study thus describes the immunomodulatory and antioxidant effects of Myrtenol on B[a]P-induced immune destruction.

Testosterone with Silymarin Improves Diabetes-obesity Comorbidity Complications by Modulating Inflammatory Responses and CYP7A1/ACC Gene Expressions in Rats.

BACKGROUND: The co-morbidity of DMOB has become increasingly problematic among the world's population because of a high-calorie diet and sedentary lifestyle. DMOB is associated with lower testosterone (TN) levels, the male sex hormone. The phytochemical compound silymarin (SN) exerts antidiabetic activity by modifying ß-cells and anti-obesity activity by inhibiting adipogenesis by methylxanthine. AIM: The goal of this study was to find out how well testosterone (TN) with silymarin (SN) protects against oxidative stress and inflammation in the liver of the experimental rats with type 2 diabetes (T2D) and obesity (DMOB). OBJECTIVES: The present study evaluates the efficacy of TN and SN combination (TNSN) on the levels of the potential parameters, such as body mass, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profile, enzymatic and non-enzymatic antioxidants, proinflammatory cytokines, gene expression pathways, and histopathology in a DMOB comorbidity rat model. METHODS: Male Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 20 weeks with an administration of a single dose of streptozotocin (STZ) i.p. injection (30 mg/kg) on the 9th week of the study. The procedure was to develop the DMOB co-morbidity model in the experimental animals. Co-treatment of TN and SN administration were followed throughout the experiment. Rats were sacrificed after overnight fasting to collect serum and liver tissue samples. Samples were analyzed using a clinical chemistry automated analyzer, spectrophotometry, and quantitative real-time PCR (qPCR) methods and protocols. RESULTS: Analyses of body mass changes, serum marker enzymes, fasting glucose levels, HbA1c levels, lipid profiles, enzymatic and non-enzymatic antioxidants, TNF-α, IL-6, adiponectin, CYP7A1, ACC expression pathways, and histopathology showed significant abnormal levels (P ≤ 0.05) in the pathological group. These were efficiently treated to normal by the administration of TNSN. CONCLUSION: These results concluded that TNSN exerted protective efficacy against the liver abnormalities in the co-morbidity of the DMOB rat model.

Precise Construction of Dual-Promising Anticancer Drugs Associated with Gold Nanomaterials on Glioma Cancer Cells.

Multiple chemodrugs with nanotechnology have proven to be an effective cancer treatment technique. When taken combined, cabazitaxel (CTX) and cisplatin (PT) have more excellent cytotoxic effects than drugs used alone in the chemotherapy of several different cancers. However, several severe side effects are associated with using these chemotherapy drugs in cancer patients. Gold nanomaterials (AuNMs) are promising as drug carriers because of their small diameter, easy surface modifications, good biocompatibility, and strong cell penetration. This work aimed to determine the CTX and PT encapsulated with AuNMs against human glioma U87 cancer cells. The fabrication of the AuNMs achieved a negative surface charge, polydispersity index, and the mean sizes. The combined cytotoxic effect of CTX and PT bound to AuNMs was greater than that of either drug alone when tested on U87 cells. The half inhibitory concentration (IC50) values for free PT were 54.7 µg/mL (at 24 h) and 4.8 g µg/mL (at 72 h). Results acquired from the MTT assay show cell growth decreases time- and concentration-dependent AuNMs, free CTX, free PT, and AuNMs@CTX/PT-induced cytotoxicity and, ultimately, the cell death of U87 cells via apoptosis. The biochemical apoptosis staining techniques investigated the cells' morphological changes of the cells (acridine orange and ethidium bromide (AO-EB) and nuclear staining (DAPI) techniques). The AO-EB and nuclear staining results reveal that the NPs effectively killed cancer cells. Furthermore, the flow cytometry analysis examined the mode of cell death. Therefore, AuNMs@CTX/PT has excellent potential in the cancer therapy of different cancer cells.

Diterpene Coronarin Attenuates Lipopolysaccharide-Induced Acute Lung Injury in Both In Vivo and In Vitro Models.

Acute lung injury (ALI) is a clinical condition occurs due to severe systemic inflammatory response for clinical stimulus like pneumonia, sepsis, trauma, aspiration, inhalation of toxic gases, and pancreatitis. Disruption of alveolar barriers, activation of macrophages, infiltration of neutrophils, and proinflammatory cytokines are the vital events occurs during ALI. The drugs which inhibit these inflammatory response can protect lungs from inflammatory insults. In this study, we examined the potency of phytochemical coronarin, a diterpene which have been proven to possess anti-inflammatory, antioxidant, antiangiogenic, and antitumor activities. Healthy BALB/c mice were induced to acute lung injury with intra-tracheal administration of LPS and then treated with 5 and 10 mg/kg concentration of coronarin. The wet/dry lung weight of mice were estimated to assess the induction of pulmonary edema. BALF fluid was analyzed for protein concentrations and immune cells count. Myeloperoxidase activity and levels of chemokines MCP-2 and MIP-2, iNOS, COX-2, and PGE-2 were quantified to assess the immunomodulatory effect of coronarin against LPS-induced ALI. The levels of proinflammatory cytokines was measured to examine the anti-inflammatory property of coronarin, and it was confirmed with histopathological analysis of the lung tissue. Murine RAW 264.7 cells were utilized for the in vitro analysis. Cell cytoxicity and cytoprotective property of coronarin was assessed with MTT assay in LPS-treated Murine RAW 264.7. The anti-inflammatory property of coronarin was further confirmed in in vitro condition by estimating the levels of pro-inflammatory cytokines in coronarin-treated and untreated LPS-induced cells. Overall, our in vivo and in vitro results confirm coronarin significantly inhibited the infiltration of neutrophils prevented immunodulatory activity and synthesis of proinflammatory cytokines and alleviated the acute lung injury induced by LPS. Coronarin is a potent anti-inflammatory drug which can be subjected to further research to be prescribed as drug for ALI.

Adsorption Characteristics of Hair Dyes Removal from Aqueous Solution onto Oak Cupules Powder Coated with ZnO.

Three hair dyes of Arianor madder red 306003 (R), Arian or Straw Yellow 306005 (Y), and Arianor ebony 306020 (E) were removed from an aqueous solution in a batch mode using a powder of oak cupules coated with ZnO (COZ). The COZ-adsorbent material was characterized in terms of XRD, FT-IR, and SEM analysis. The best conditions for the uptake of hair dyes by COZ were investigated. For Y dye, the best uptake was estimated on 0.06 g of COZ at 7.0 pH for 150 min. The E dye uptake requires 120 min on 0.05 g of COZ at 9.0 pH. For E hair dye, kinetic data revealed a pseudo-first-order model for E hair dye and a pseudo-second-order model for R and Y. Equilibrium data exhibited consistency with the Langmuir isotherm model for the adsorption of E dye onto COZ, and the Freundlich isotherm model for the adsorption of R and Y hair dyes onto COZ. Isotherms models of D-R and Temkin were also examined. The thermodynamic parameters (-ve ∆G and +ve ∆H and ∆S) demonstrated that the removal of hair dyes by COZ is spontaneous, endothermic, and feasible. The adsorption capacity of COZ for R, Y, and E uptake was found to be 55.5, 52.6, and 135.1 mg·g-1, respectively. Furthermore, COZ reusability was demonstrated after five cycles of regeneration, with a negligible decline in adsorption extent (13.08%, 13.85, and 10.20% for R, Y, and E, respectively) in comparison to its initial capacity.

Preparation and characterisation of ciprofloxacin-loaded silver nanoparticles for drug delivery.

Silver nanoparticles (AgNPs) have shown potential applications in drug delivery. In this study, the AgNPs was prepared from silver nitrate in the presence of alginate as a capping agent. The ciprofloxacin (Cipro) was loaded on the surface of AgNPs to produce Cipro-AgNPs nanocomposite. The characteristics of the Cipro-AgNPs nanocomposite were studied by X-ray diffraction (XRD), UV-Vis, transmission electron microscopy (TEM), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), Fourier-transform infra-red analysis (FT-IR) and zeta potential analyses. The XRD of AgNPs and Cipro-AgNPs nanocomposite data showed that both have a crystalline structure in nature. The FT-IR data indicate that the AgNPs have been wrapped by the alginate and loaded with the Cipro drug. The TEM image showed that the Cipro-AgNPs nanocomposites have an average size of 96 nm with a spherical shape. The SEM image for AgNPs and Cipro-AgNPs nanocomposites confirmed the needle-lumpy shape. The zeta potential for Cipro-AgNPs nanocomposites exhibited a positive charge with a value of 6.5 mV. The TGA for Cipro-AgNPs nanocomposites showed loss of 79.7% in total mass compared to 57.6% for AgNPs which is due to the Cipro loaded in the AgNPs. The release of Cipro from Cipro-AgNPs nanocomposites showed slow release properties which reached 98% release within 750 min, and followed the Hixson-Crowell kinetic model. In addition, the toxicity of AgNPs and Cipro-AgNPs nanocomposites was evaluated using normal (3T3) cell line. The present work suggests that Cipro-AgNPs are suitable for drug delivery.

Graphene oxide-ellagic acid nanocomposite as effective anticancer and antimicrobial agent.

In this study, ellagic acid (ELA), a skin anticancer drug, is capped on the surface(s) of functionalised graphene oxide (GO) nano-sheets through electrostatic and π-π staking interactions. The prepared ELA-GO nanocomposite have been thoroughly characterised by using eight techniques: Fourier-transform infrared spectroscopy (FTIR), zeta potential, X-ray diffraction (XRD), thermogravimetric analysis (TGA), Raman spectroscopy, atomic force microscopy (AFM) topographic imaging, transmission electron microscopy (TEM), and surface morphology via scanning electron microscopy (SEM). Furthermore, ELA drug loading and release behaviours from ELA-GO nanocomposite were studied. The ELA-GO nanocomposite has a uniform size distribution averaging 88 nm and high drug loading capacity of 30 wt.%. The in vitro drug release behaviour of ELA from the nanocomposite was investigated by UV-Vis spectrometry at a wavelength of λmax 257 nm. The data confirmed prolonged ELA release over 5000 min at physiological pH (7.4). Finally, the IC50 of this ELA-GO nanocomposite was found to be 6.16 µg/ml against B16 cell line; ELA and GO did not show any cytotoxic effects up to 50 µg/ml on the same cell lines.

Chlorambucil-Iron Oxide Nanoparticles as a Drug Delivery System for Leukemia Cancer Cells.

INTRODUCTION: Traditional cancer therapies may have incomplete eradication of cancer or destroy the normal cells. Nanotechnology solves the demerit by a guide in surgical resection of tumors, targeted chemotherapies, selective to cancerous cells, etc. This new technology can reduce the risk to the patient and automatically increased the probability of survival. Toward this goal, novel iron oxide nanoparticles (IONPs) coupled with leukemia anti-cancer drug were prepared and assessed. METHODS: The IONPs were prepared by the co-precipitation method using Fe+3/Fe+2ratio of 2:1. These IONPs were used as a carrier for chlorambucil (Chloramb), where the IONPs serve as the cores and chitosan (CS) as a polymeric shell to form Chloramb-CS-IONPs. The products were characterized using transmission electron microscopy (TEM), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) analysis, Fourier transform infrared spectroscopy (FTIR), vibrating sample magnetometry (VSM) analyses, and thermal gravimetric analysis (TGA). RESULTS: The as-prepared IONPs were found to be magnetite (Fe3O4) and were coated by the CS polymer/Chloramb drug for the formation of the Chloramb-CS-IONPs. The average size for CS-IONPs and Chloramb-CS-IONPs nanocomposite was found to be 15 nm, with a drug loading of 19% for the letter. The release of the drug from the nanocomposite was found to be of a controlled-release manner with around 89.9% of the drug was released within about 5000 min and governed by the pseudo-second order. The in vitro cytotoxicity studies of CS-IONPs and Chloramb-CS-IONPs nanocomposite were tested on the normal fibroblast cell lines (3T3) and leukemia cancer cell lines (WEHI). Chloramb in Chloramb-CS-IONPs nanocomposite was found to be more efficient compared to its free form. CONCLUSION: This work shows that Chloramb-CS-IONPs nanocomposite is a promising candidate for magnetically targeted drug delivery for leukemia anti-cancer agents.

A Statistical Study on the Development of Metronidazole-Chitosan-Alginate Nanocomposite Formulation Using the Full Factorial Design.

The goal of this study was to develop and statistically optimize the metronidazole (MET), chitosan (CS) and alginate (Alg) nanoparticles (NP) nanocomposites (MET-CS-AlgNPs) using a (21 × 31 × 21) × 3 = 36 full factorial design (FFD) to investigate the effect of chitosan and alginate polymer concentrations and calcium chloride (CaCl2) concentration ondrug loading efficiency(LE), particle size and zeta potential. The concentration of CS, Alg and CaCl2 were taken as independent variables, while drug loading, particle size and zeta potential were taken as dependent variables. The study showed that the loading efficiency and particle size depend on the CS, Alg and CaCl2 concentrations, whereas zeta potential depends only on the Alg and CaCl2 concentrations. The MET-CS-AlgNPs nanocomposites were characterized by X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), scanning electron microscopy (SEM) and in vitro drug release studies. XRD datashowed that the crystalline properties of MET changed to an amorphous-like pattern when the nanocomposites were formed.The XRD pattern of MET-CS-AlgNPs showed reflections at 2θ = 14.2° and 22.1°, indicating that the formation of the nanocompositesprepared at the optimum conditions havea mean diameter of (165±20) nm, with a MET loading of (46.0 ± 2.1)% and a zeta potential of (-9.2 ± 0.5) mV.The FTIR data of MET-CS-AlgNPs showed some bands of MET, such as 3283, 1585 and 1413 cm-1, confirming the presence of the drug in the MET-CS-AlgNPs nanocomposites. The TGA for the optimized sample of MET-CS-AlgNPs showed a 70.2% weight loss compared to 55.3% for CS-AlgNPs, and the difference is due to the incorporation of MET in the CS-AlgNPs for the formation of MET-CS-AlgNPs nanocomposites. The release of MET from the nanocomposite showed sustained-release properties, indicating the presence of an interaction between MET and the polymer. The nanocomposite shows a smooth surface and spherical shape. The release profile of MET from its MET-CS-AlgNPs nanocomposites was found to be governed by the second kinetic model (R2 between 0.956-0.990) with more than 90% release during the first 50 h, which suggests that the release of the MET drug can be extended or prolonged via the nanocomposite formulation.

Synthesis, characterization, and antimicrobial activity of an ampicillin-conjugated magnetic nanoantibiotic for medical applications.

Because of their magnetic properties, magnetic nanoparticles (MNPs) have numerous diverse biomedical applications. In addition, because of their ability to penetrate bacteria and biofilms, nanoantimicrobial agents have become increasingly popular for the control of infectious diseases. Here, MNPs were prepared through an iron salt coprecipitation method in an alkaline medium, followed by a chitosan coating step (CS-coated MNPs); finally, the MNPs were loaded with ampicillin (amp) to form an amp-CS-MNP nanocomposite. Both the MNPs and amp-CS-MNPs were subsequently characterized and evaluated for their antibacterial activity. X-ray diffraction results showed that the MNPs and nanocomposites were composed of pure magnetite. Fourier transform infrared spectra and thermogravimetric data for the MNPs, CS-coated MNPs, and amp-CS-MNP nanocomposite were compared, which confirmed the CS coating on the MNPs and the amp-loaded nanocomposite. Magnetization curves showed that both the MNPs and the amp-CS-MNP nanocomposites were superparamagnetic, with saturation magnetizations at 80.1 and 26.6 emu g(-1), respectively. Amp was loaded at 8.3%. Drug release was also studied, and the total release equilibrium for amp from the amp-CS-MNPs was 100% over 400 minutes. In addition, the antimicrobial activity of the amp-CS-MNP nanocomposite was determined using agar diffusion and growth inhibition assays against Gram-positive bacteria and Gram-negative bacteria, as well as Candida albicans. The minimum inhibitory concentration of the amp-CS-MNP nanocomposite was determined against bacteria including Mycobacterium tuberculosis. The synthesized nanocomposites exhibited antibacterial and antifungal properties, as well as antimycobacterial effects. Thus, this study introduces a novel ß-lactam antibacterial-based nanocomposite that can decrease fungus activity on demand for numerous medical applications.

Antimicrobial and controlled release studies of a novel nystatin conjugated iron oxide nanocomposite.

Nystatin is a tetraene diene polyene antibiotic showing a broad spectrum of antifungal activity. In the present study, we prepared a nystatin nanocomposite (Nyst-CS-MNP) by loading nystatin (Nyst) on chitosan (CS) coated magnetic nanoparticles (MNPs). The magnetic nanocomposites were characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), thermogravimetry analysis (TGA), vibrating sample magnetometer (VSM), and scanning electron microscopy (SEM). The XRD results showed that the MNPs and nanocomposite are pure magnetite. The FTIR analysis confirmed the binding of CS on the surface of the MNPs and also the loading of Nyst in the nanocomposite. The Nyst drug loading was estimated using UV-Vis instrumentation and showing a 14.9% loading in the nanocomposite. The TEM size image of the MNPs, CS-MNP, and Nyst-CS-MNP was 13, 11, and 8 nm, respectively. The release profile of the Nyst drug from the nanocomposite followed a pseudo-second-order kinetic model. The antimicrobial activity of the as-synthesized Nyst and Nyst-CS-MNP nanocomposite was evaluated using an agar diffusion method and showed enhanced antifungal activity against Candida albicans. In this manner, this study introduces a novel nanocomposite that can decrease fungus activity on-demand for numerous medical applications.

Release behavior and toxicity profiles towards leukemia (WEHI-3B) cell lines of 6-mercaptopurine-PEG-coated magnetite nanoparticles delivery system.

The coating of an active drug, 6-mercaptopurine, into the iron oxide nanoparticles-polyethylene glycol (FNPs-PEG) in order to form a new nanocomposite, FPEGMP-2, was accomplished using coprecipitation technique. The resulting nanosized with a narrow size distribution magnetic polymeric particles show the superparamagnetic properties with 38.6 emu/g saturation magnetization at room temperature. Fourier transform infrared spectroscopy and the thermal analysis study supported the formation of the nanocomposite and the enhancement of thermal stability in the resulting nanocomposite comparing with its counterpart in free state. The loading of 6-mercaptopurine (MP) in the FPEGMP-2 nanocomposite was estimated to be about 5.6% and the kinetic experimental data properly correlated with the pseudo-second order model. Also, the release of MP from the FPEGMP-2 nanocomposite shows the sustained release manner which is remarkably lower in phosphate buffered solution at pH 7.4 than pH 4.8, due to different release mechanism. The maximum percentage release of MP from the nanocomposite reached about 60% and 97% within about 92 and 74 hours when exposed to pH 7.4 and 4.8, respectively.

Preparation of Tween 80-Zn/Al-levodopa-layered double hydroxides nanocomposite for drug delivery system.

We incorporated anti-Parkinsonian drug, levodopa (dopa), in Zn/Al-LDH by coprecipitation method to form dopa-LDH nanocomposite. Further coating of Tween-80 on the external surfaces of dopa-LDH nanocomposite was achieved through the oxygen of C=O group of Tween-80 with the layer of dopa-LDH nanocomposite. The final product is called Tween-dopa-LDH nanocomposite. The X-ray diffraction indicates that the Tween-dopa-LDH nanocomposite was formed by aggregation structure. From the TGA data, the Tween-80 loading on the surface of LDH and dopa-LDH was 8.6 and 7.4%, respectively. The effect of coating process on the dopa release from Tween-dopa-LDH nanocomposite was also studied. The release from Tween-dopa-LDH nanocomposite shows slower release compared to the release of the drug from dopa-LDH nanocomposite as done previously in our study, presumably due to the retarding shielding effect. The cell viability study using PC12 showed improved viability with Tween-80 coating on dopa-LDH nanocomposite as studied by mitochondrial dehydrogenase activity (MTT assay).

In vitro sustained release study of gallic acid coated with magnetite-PEG and magnetite-PVA for drug delivery system.

The efficacy of two nanocarriers polyethylene glycol and polyvinyl alcohol magnetic nanoparticles coated with gallic acid (GA) was accomplished via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis, and TEM. X-ray diffraction and TEM results showed that Fe3O4 nanoparticles were pure iron oxide having spherical shape with the average diameter of 9 nm, compared with 31 nm and 35 nm after coating with polyethylene glycol-GA (FPEGG) and polyvinyl alcohol-GA (FPVAG), respectively. Thermogravimetric analyses proved that after coating the thermal stability was markedly enhanced. Magnetic measurements and Fourier transform infrared (FTIR) revealed that superparamagnetic iron oxide nanoparticles could be successfully coated with two polymers (PEG and PVA) and gallic acid as an active drug. Release behavior of gallic acid from two nanocomposites showed that FPEGG and FPVAG nanocomposites were found to be sustained and governed by pseudo-second-order kinetics. Anticancer activity of the two nanocomposites shows that the FPEGG demonstrated higher anticancer effect on the breast cancer cell lines in almost all concentrations tested compared to FPVAG.

Toxicity and metabolism of layered double hydroxide intercalated with levodopa in a Parkinson's disease model.

Layered hydroxide nanoparticles are generally biocompatible, and less toxic than most inorganic nanoparticles, making them an acceptable alternative drug delivery system. Due to growing concern over animal welfare and the expense of in vivo experiments both the public and the government are interested to find alternatives to animal testing. The toxicity potential of zinc aluminum layered hydroxide (ZAL) nanocomposite containing anti-Parkinsonian agent may be determined using a PC 12 cell model. ZAL nanocomposite demonstrated a decreased cytotoxic effect when compared to levodopa on PC12 cells with more than 80% cell viability at 100 µg/mL compared to less than 20% cell viability in a direct levodopa exposure. Neither levodopa-loaded nanocomposite nor the un-intercalated nanocomposite disturbed the cytoskeletal structure of the neurogenic cells at their IC50 concentration. Levodopa metabolite (HVA) released from the nanocomposite demonstrated the slow sustained and controlled release character of layered hydroxide nanoparticles unlike the burst uptake and release system shown with pure levodopa treatment.

Synthesis, characterization, controlled release, and antibacterial studies of a novel streptomycin chitosan magnetic nanoantibiotic.

This study describes the preparation, characterization, and controlled release of a streptomycin-chitosan-magnetic nanoparticle-based antibiotic in an effort to improve the treatment of bacterial infections. Specifically, chitosan-magnetic nanoparticles were synthesized by an incorporation method and were characterized by Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetric analysis, and vibrating sample magnetometry. Streptomycin was incorporated into the nanoparticles to form a streptomycin-coated chitosan-magnetic nanoparticle (Strep-CS-MNP) nanocomposite. The release profiles showed an initially fast release, which became slower as time progressed. The percentage of drug released after 350 minutes was around 100%, and the best fit mathematical model for drug release was the pseudo-second order model. The Strep-CS-MNP nanocomposite showed enhanced antibacterial activity against methicillin-resistant Staphylococcus aureus. This study forms a significant basis for further investigation of the Strep-CS-MNP nanocomposite in the treatment of various bacterial infections.

Novel kojic acid-polymer-based magnetic nanocomposites for medical applications.

Iron oxide magnetic nanoparticles (MNPs) were synthesized by the coprecipitation of iron salts in sodium hydroxide followed by coating separately with chitosan (CS) and polyethylene glycol (PEG) to form CS-MNPs and PEG-MNPs nanoparticles, respectively. They were then loaded with kojic acid (KA), a pharmacologically bioactive natural compound, to form KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The MNPs and their nanocomposites were characterized using powder X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, vibrating sample magnetometry, and scanning electron microscopy. The powder X-ray diffraction data suggest that all formulations consisted of highly crystalline, pure magnetite Fe3O4. The Fourier transform infrared spectroscopy and thermogravimetric analysis confirmed the presence of both polymers and KA in the nanocomposites. Magnetization curves showed that both nanocomposites (KA-CS-MNPs and KA-PEG-MNPs) were superparamagnetic with saturation magnetizations of 8.1 emu/g and 26.4 emu/g, respectively. The KA drug loading was estimated using ultraviolet-visible spectroscopy, which gave a loading of 12.2% and 8.3% for the KA-CS-MNPs and KA-PEG-MNPs nanocomposites, respectively. The release profile of the KA from the nanocomposites followed a pseudo second-order kinetic model. The agar diffusion test was performed to evaluate the antimicrobial activity for both KA-CS-MNPs and KA-PEG-MNPs nanocomposites against a number of microorganisms using two Gram-positive (methicillin-resistant Staphylococcus aureus and Bacillus subtilis) and one Gram-negative (Salmonella enterica) species, and showed some antibacterial activity, which could be enhanced in future studies by optimizing drug loading. This study provided evidence for the promise for the further investigation of the possible beneficial biological activities of KA and both KA-CS-MNPs and KA-PEG-MNPs nanocomposites in nanopharmaceutical applications.

Arginine-chitosan- and arginine-polyethylene glycol-conjugated superparamagnetic nanoparticles: Preparation, cytotoxicity and controlled-release.

Iron oxide magnetic nanoparticles (MNPs) can be used in targeted drug delivery systems for localized cancer treatment. MNPs coated with biocompatible polymers are useful for delivering anticancer drugs. Iron oxide MNPs were synthesized via co-precipitation method then coated with either chitosan (CS) or polyethylene glycol (PEG) to form CS-MNPs and PEG-MNPs, respectively. Arginine (Arg) was loaded onto both coated nanoparticles to form Arg-CS-MNP and Arg-PEG-MNP nanocomposites. The X-ray diffraction results for the MNPs and the Arg-CS-MNP and Arg-PEG-MNPs nanocomposites indicated that the iron oxide contained pure magnetite. The amount of CS and PEG bound to the MNPs were estimated via thermogravimetric analysis and confirmed via Fourier transform infrared spectroscopy analysis. Arg loading was estimated using UV-vis measurements, which yielded values of 5.5% and 11% for the Arg-CS-MNP and Arg-PEG-MNP nanocomposites, respectively. The release profile of Arg from the nanocomposites followed a pseudo-second-order kinetic model. The cytotoxic effects of the MNPs, Arg-CS-MNPs, and Arg-PEG-MNPs were evaluated in human cervical carcinoma cells (HeLa), mouse embryonic fibroblast cells (3T3) and breast adenocarcinoma cells (MCF-7). The results indicate that the MNPs, Arg-CS-MNPs, and Arg-PEG-MNPs do not exhibit cytotoxicity toward 3T3 and HeLa cells. However, treatment of the MCF-7 cells with the Arg-CS-MNP and Arg-PEG-MNP nanocomposites reduced the cancer cell viability with IC50 values of 48.6 and 42.6 µg/mL, respectively, whereas the MNPs and free Arg did not affect the viability of the MCF-7 cells.

Antituberculosis nanodelivery system with controlled-release properties based on para-amino salicylate-zinc aluminum-layered double-hydroxide nanocomposites.

We report the intercalation and characterization of para-amino salicylic acid (PASA) into zinc/aluminum-layered double hydroxides (ZLDHs) by two methods, direct and indirect, to form nanocomposites: PASA nanocomposite prepared by a direct method (PASA-D) and PASA nanocomposite prepared by an indirect method (PASA-I). Powder X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis revealed that the PASA drugs were accommodated within the ZLDH interlayers. The anions of the drug were accommodated as an alternate monolayer (along the long-axis orientation) between ZLDH interlayers. Drug loading was estimated to be 22.8% and 16.6% for PASA-D and PASA-I, respectively. The in vitro release properties of the drug were investigated in physiological simulated phosphate-buffered saline solution of pH 7.4 and 4.8. The release followed the pseudo-second-order model for both nanocomposites. Cell viability (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide [MTT] assays) was assessed against normal human lung fibroblast MRC-5 and 3T3 mouse fibroblast cells at 24, 48, and 72 hours. The results showed that the nanocomposite formulations did not possess any cytotoxicity, at least up to 72 hours.