Nanotechnology in drug delivery: the need for more cell culture based studies in screening

Advances in biomedical science are leading to upsurge synthesis of nanodelivery systems for drug delivery. The systems were characterized by controlled, targeted and sustained drug delivery ability. Humans are the target of these systems, hence, animals whose systems resembles humans were used to predict outcome. Thus, increasing costs in money and time, plus ethical concerns over animal usage. However, with consideration and planning in experimental conditions, in vitro pharmacological studies of the nanodelivery can mimic the in vivo system. This can function as a simple method to investigate the effect of such materials without endangering animals especially at screening phase

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)

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

Culture of Chironomid larvae using two different feeds

Rearing of chironomid larvae was conducted under laboratory conditions, to study the effect of two different feed (Yeast and Scenedesmus) on the growth rate (weight & length) and hemoglobin content of chironomid larvae. The lengths of Chironomid larvae were measured weekly with the help of a calibrated microscope and the weight was determined using a sensitive weighing balance (SE2 Ultra-microbalance). The hemoglobin concentration was determined using cyano-methemoglobin method according to Van Kampen and Zijlstra (1961) and Tentori and Salvati (1981). Larvae had mean initial length 2.3mm and mean weight 2.0µg. Larvae fed with yeast showed final mean length of 3.75±0.17mm and weight of 4.36±o.21µg, while those fed with scenedesmus showed final mean length of 3.16±0.17mm and weight of 4.09±0.11µg. The hemoglobin count of chironomids fed with yeast was 0.684µgHbmg-1 while that of the larvae fed scenedesmus was 0.649µgHbmg-1. Mortality of 5 chironomids was observed in the yeast setup against 8 observed in the setup with scenedesmus, while 41 burrowed chironomids was observed in the scenedesmus setup against 25 observed in the yeast setup. ANOVA reveals significant difference in the effect of both feeds on the growth rate of the chironomid larvae (P<0.05). The results among others at the end of the exposure demonstrated that yeast is more suitable for chironomid culture than scenedesmus. This work therefore revealed the suitability of yeast in chironomid culture over scenedesmus. Keywords: culture, Chironomid, larvae, yeast, Scenedesmus, hemoglobi

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

Effect of Gelatin-Stabilized Copper Nanoparticles on Catalytic Reduction of Methylene Blue

The synthesis of copper nanoparticles was carried out with gelatin as a stabilizer by reducing CuSO4.5H2O ions using hydrazine. Ascorbic acid and aqueous NaOH were also used as an antioxidant and pH controller, respectively. The effects of NaOH, hydrazine, and concentration of gelatin as stabilizer were studied. The synthesized copper nanoparticles were characterized by UV-vis spectroscopy, XRD, zeta potential measurements, FTIR, EDX, FESEM, and TEM. The formation of CuNPs@Gelatin is initially confirmed by UV-vis spectroscopic analysis with the characteristic band at 583 nm. XRD and TEM reports revealed that CuNPs@Gelatin (0.75 wt.%) is highly crystalline and spherical in shape with optimum average size of 4.21 ± 0.95 nm. FTIR studies indicated the presence of amide group on the surface of the CuNPs indicating the stability of CuNPs which is further supported by zeta potential measurements with the negative optimum value of −37.90 ± 0.6 mV. The CuNPs@G4 showed a good catalytic activity against methylene blue (MB) reduction using NaBH4 as a reducing agent in an aqueous solution. The best enhanced properties of CuNPs@G4 were found for the 0.75 wt.% gelatin concentration. Thermodynamic parameters (ΔH and ΔS) indicate that under the studied temperature, the reduction of MB by CuNPs@G4 is not feasible and had endothermic in nature

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

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

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