Cytotoxic profiles of a nanodrug delivery based on 6-mercaptopurine-coated magnetite-peg nanoparticles towards leukemia (WEHI-3B) cell lines

A drug active, 6-mercaptopurine (MP) was coated on the surface of Fe3O4-PEG nanoparticles using co-precipitation method in order to form a new magnetic nanocomposite (FPEGMP). The physico-chemical properties of the nanocomposite were studied via X-ray diffraction, infrared spectroscopy, magnetic measurements, thermal analysis and transmission electron microscopy. The resulting superparamagnetic nanocomposite has spherical shape with average particle size diameter of 11 nm. Thermal analyses and Fourier transform infrared (FTIR) spectroscopy revealed the formation of PEG-MP on the surface of iron oxide nanoparticles and the enhancement of the thermal stability of the nanocomposite compared to its counterpart, free 6-mercaptopurine. Release behavior of MP from FPEGMP nanocomposite was found to be sustained and governed by pseudo-second order kinetic. The maximum percentage release of MP from FPEGMP nanocomposite reached about 60% and 97% within approximately 92 and 72 hours when exposed to aqueous solutions at pH 7.4 and pH 4.8, respectively. Anti-cancer activity of the nanocomposite shows that the choice of coating material as well as the percentage of loading of the active agent could affect the cytotoxic activity of nanocomposite towards the mouse myelomonocytic leukemic cell line (WEHI-3B)

Acute oral toxicity and biodistribution study of zinc aluminium-levodopa nanocomposite

Layered double hydroxide (LDH) is an inorganic-organic nano-layered material that harbours drug between its two-layered sheets, forming a sandwich-like structure. It is attracting a great deal of attention as an alternative drug delivery (nanodelivery) system in the field of pharmacology due to their relative low toxic potential. The production of these nanodelivery systems, aimed at improving human health through decrease toxicity, targeted delivery of the active compound to areas of interest with sustained release ability. In this study, we administered zinc-aluminium-LDH-levodopa nanocomposite (ZAL) and zinc-aluminium nanocomposite (ZA) to Sprague Dawley rats to evaluate for acute oral toxicity following OECD guidelines. The oral administration of ZAL and ZA at a limit dose of 2,000 mg/kg produced neither mortality nor acute toxic signs throughout 14 days of the observation. The percentage of body weight gain of the animals showed no significant difference between control and treatment groups. Animal from the two treated groups gained weight continuously over the study period, which was shown to be significantly higher than the weight at the beginning of the study (P < 0.05). Biochemical analysis of animal serum showed no significant difference between rats treated with ZAL, ZA and controls. There was no gross lesion or histopathological changes observed in vital organs of the rats. The results suggested that ZAL and ZA at 2,000 mg/kg body weight in rats do not induce acute toxicity in the animals. Elemental analysis of tissues of treated animals demonstrated the wider distribution of the nanocomposite including the brain. In summary, findings of acute toxicity tests in this study suggest that zinc-aluminium nanocomposite intercalated with and the un-intercalated were safe when administered orally in animal models for short periods of time. It also highlighted the potential distribution ability of Tween-80 coated nanocomposite after oral administration

Development of a controlled-release anti-parkinsonian nanodelivery system using levodopa as the active agent.

A new layered organic-inorganic nanocomposite material with an anti-parkinsonian active compound, L-3-(3,4-dihydroxyphenyl) alanine (levodopa), intercalated into the inorganic interlayers of a Zn/Al-layered double hydroxide (LDH) was synthesized using a direct coprecipitation method. The resulting nanocomposite was composed of the organic moiety, levodopa, sandwiched between Zn/Al-LDH inorganic interlayers. The basal spacing of the resulting nano-composite was 10.9 Å. The estimated loading of levodopa in the nanocomposite was approximately 16% (w/w). A Fourier transform infrared study showed that the absorption bands of the nanocomposite were characteristic of both levodopa and Zn/Al-LDH, which further confirmed intercalation, and that the intercalated organic moiety in the nanocomposite was more thermally stable than free levodopa. The resulting nanocomposite showed sustained-release properties, so can be used in a controlled-release formulation. Cytotoxicity analysis using an MTT assay also showed increased cell viability of 3T3 cells exposed to the newly synthesized nanocomposite compared with those exposed to pure levodopa after 72 hours of exposure

Preparation and characterization of 6-mercaptopurine-coated magnetite nanoparticles as a drug delivery system

Background: Iron oxide nanoparticles are of considerable interest because of their use in magnetic recording tape, ferrofluid, magnetic resonance imaging, drug delivery, and treatment of cancer. The specific morphology of nanoparticles confers an ability to load, carry, and release different types of drugs. Methods and results: We synthesized super paramagnetic nanoparticles containing pure iron oxide with a cubic inverse spinal structure. Fourier transform infrared spectra confirmed that these Fe3O4 nanoparticles could be successfully coated with active drug, and thermogravimet-ric and differential thermogravimetric analyses showed that the thermal stability of iron oxide nanoparticles coated with chitosan and 6-mercaptopurine (FCMP) was markedly enhanced. The synthesized Fe3O4 nanoparticles and the FCMP nanocomposite were generally spherical, with an average diameter of 9 nm and 19 nm, respectively. The release of 6-mercaptopurine from the FCMP nanocomposite was found to be sustained and governed by pseudo-second order kinetics. In order to improve drug loading and release behavior, we prepared a novel nanocomposite (FCMP-D), ie, Fe3O4 nanoparticles containing the same amounts of chitosan and 6-mercaptopurine but using a different solvent for the drug. The results for FCMP-D did not demonstrate "burst release" and the maximum percentage release of 6-mercaptopurine from the FCMP-D nanocomposite reached about 97.7% and 55.4% within approximately 2,500 and 6,300 minutes when exposed to pH 4.8 and pH 7.4 solutions, respectively. By MTT assay, the FCMP nanocomposite was shown not to be toxic to a normal mouse fibroblast cell line. Conclusion: Iron oxide coated with chitosan containing 6-mercaptopurine prepared using a coprecipitation method has the potential to be used as a controlled-release formulation. These nanoparticles may serve as an alternative drug delivery system for the treatment of cancer, with the added advantage of sparing healthy surrounding cells and tissue

Controlled-release formulation of perindopril erbumine loaded PEG-coated magnetite nanoparticles for biomedical applications

Iron oxide nanoparticles (FNPs) were synthesized due to low toxicity and their ability to immobilize biological materials on their surfaces by the coprecipitation of iron salts in ammonia hydroxide followed by coating it with polyethylene glycol (PEG) to minimize the aggregation of iron oxide nanoparticles and enhance the effect of nanoparticles for biological applications. Then, the FNPs–PEG was loaded with perindopril erbumine (PE), an antihypertensive compound to form a new nanocomposite (FPEGPE). Transmission electron microscopy results showed that there are no significant differences between the sizes of FNPs and FPEGPE nanocomposite. The existence of PEG–PE was supported by the FTIR and TGA analyses. The PE loading (10.3 %) and the release profiles from FPEGPE nanocomposite were estimated using ultraviolet–visible spectroscopy which showed that up to 60.8 and 83.1 % of the adsorbed drug was released in 4223 and 1231 min at pH 7.4 and 4.8, respectively. However, the release of PE was completed very fast from a physical mixture (FNPs–PEG–PE) after 5 and 7 min at pH 4.8 and 7.4, respectively, which reveals that the release of PE from the physical mixture is not in the sustained-release manner. Cytotoxicity study showed that free PE presented slightly higher toxicity than the FNPs and FPEGPE nanocomposite. Therefore, the decrease toxicity against mouse normal fibroblast (3T3) cell lines prospective of this nanocomposite together with controlled-release behavior provided evidence of the possible beneficial biological activities of this new nanocomposite for nanopharmaceutical applications for both oral and non-oral routes

The modulatory effect of Moringa oleifera leaf extract on endogenous antioxidant systems and inflammatory markers in acetaminophen induced nephrotoxic mice model

N-Acetyl-p-Aminophenol (APAP), also known as acetaminophen, is the most commonly used over-the counter analgesic and antipyretic medication. However, its overdose leads to both liver and kidney damage. APAP-induced toxicity is considered as one of the primary causes of acute liver failure; numerous scientific reports have focused majorly on APAP hepatotoxicity. Alternatively, not many works approach APAP nephrotoxicity focusing on both its mechanisms of action and therapeutic exploration. Moringa oleifera (MO) is pervasive in nature, is reported to possess a surplus amount of nutrients, and is enriched with several bioactive candidates including trace elements that act as curatives for various clinical conditions. In this study, we evaluated the nephro-protective potential of MO leaf extract against APAP nephrotoxicity in male Balb/c mice. A single-dose acute oral toxicity design was implemented in this study. Group 2, 3, 4 and 5 received a toxic dose of APAP (400 mg/kg of bw, i.p) and after an hour, these groups were administered with saline (10 mL/kg), silymarin-positive control (100 mg/kg of bw, i.p), MO leaf extract (100 mg/kg of bw, i.p), and MO leaf extract (200 mg/kg bw, i.p) respectively. Group 1 was administered saline (10 mL/kg) during both the sessions. APAP-treated mice exhibited a significant elevation of serum creatinine, blood urea nitrogen, sodium, potassium and chloride levels. A remarkable depletion of antioxidant enzymes such as SOD, CAT and GSH-Px with elevated MDA levels has been observed in APAP treated kidney tissues. They also exhibited a significant rise in pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and decreased anti-inflammatory (IL-10) cytokine level in the kidney tissues. Disorganized glomerulus and dilated tubules with inflammatory cell infiltration were clearly observed in the histology of APAP treated mice kidneys. All these pathological changes were reversed in a dose-dependent manner after MO leaf extract treatment. Therefore, MO leaf extract has demonstrated some therapeutic effectiveness against APAP-induced nephrotoxicity through enhancement of the endogenous antioxidant system and a modulatory effect on specific inflammatory cytokines in kidney tissues

Preparation of chitosan nanoparticles as a drug delivery system for perindopril erbumine

Chitosan nanoparticles (CSNPs) and perindopril erbumine (PE)‐loaded chitosan nanoparticles (PE‐CSNPs) were prepared using the ionic gelation method with tripolyphosphate (TPP) as a crosslinking agent. The XRD pattern of the PE‐CSNP nanocomposite shows suppression of the peaks corresponding to crystallized chitosan due to its conversion to the amorphous form after crosslinking and PE loading. The presence of the drug in the nanocomposite was confirmed by a shift in the FTIR transmittance peak from 1,289 to 1,279 cm−1. The mean diameter of the PE‐CSNP nanocomposite was 44 nm. Analysis of the ultraviolet spectrum indicated that the loading efficiency and the encapsulation efficiency were 30.5% and 94.1%, respectively. The in vitro drug release profile was also determined by ultraviolet spectroscopy, which showed a sustained release over a period of 2 h (99.8%), starting with initial burst release (40% in 10 min). According to our results, no IC50 (the half maximal inhibitory concentration) against the 3T3 cell line was found for free PF or the PE‐CSNP nanocomposite up to 100 μg mL−1

The in vitro therapeutic activity of ellagic acid-alginate-silver nanopeprintss on breast cancer cells (MCF-7) and normal fibroblast cells (3T3)

The present work involves the development of EA-Alg-AgNPs nanocomposite based on ellagic acid (EA) as active compound. Silver nitrate was taken as the metal precursor (AgNPs) and sodium alginate (Alg) as a reducing agent. The EA-Alg-AgNPs nanocomposite was characterized using transmission electron microscopy (TEM), zeta potential, and in vitro release kinetics. The particles thus obtained were spherical in shape and having an average particles size of 10 nm, zeta potentials of –8.2 mV, and the release kinetics of EA from nanocomposite was following Hixson-Crowell kinetics models with R 2 = 0.9956. The cytotoxicity potential of free EA, Alg-AgNPs and the EA-Alg-AgNPs nanocomposite may be determined using a normal mouse fibroblast cells (3T3) and breast cancer cells (MCF-7). EA-Alg-AgNPs nanocomposite demonstrated a increased cytotoxicity effect when compared to free EA on MCF-7 cells with 15.3% cell viability at 128 μg/mL; compared to 33.5% cell viability in a direct EA exposure. It is worth mentioning the cytotoxicity of Alg-AgNPs against MCF-7 shows 28% viability at 128 μg/mL

Evaluation of in vitro efficacy of docetaxel-loaded calcium carbonate aragonite nanoparticles (DTX-CaCO3NP) on 4T1 mouse breast cancer cell line

Cockle shell-derived calcium carbonate nanoparticles have shown promising potentials as slow drug-releasing compounds in cancer chemotherapy. In this study, we evaluated the in vitro efficacy of docetaxel (DTX)-loaded CaCO3NP on 4T1 cell line. This was achieved by evaluating the following: cytotoxicity using MTT assay, fluorescence imaging, apoptosis with Annexin V assay, cell cycle analysis, scanning (SEM) and transmission electron microscopy (TEM), and scratch assay. Based on the results, DTX-CaCO3NP with a DTX concentration of 0.5 μg/mL and above had comparable cytotoxic effects with free DTX at 24 h, while all concentrations had similar cytotoxic effect on 4T1 cells at 48 and 72 h. Fluorescence and apoptosis assay showed a higher (p < 0.05) number of apoptotic cells in both free DTX and DTX-CaCO3NP groups. Cell cycle analysis showed cycle arrest at subG0 and G2/M phases in both treatment groups. SEM showed presence of cellular blebbing, while TEM showed nuclear fragmentation, apoptosis, and vacuolation in the treatment groups. Scratch assay showed lower (p < 0.05) closure in both free DTX and DTX-CaCO3NP groups. The results from this study showed that DTX-CaCO3NP has similar anticancer effects on 4T1 cells as free DTX, and since it has a slow release rate, it is a more preferred substitute for free DTX