Synthesis, Characterization, and Investigation of Doxorubicin Drug Release Properties of Poly(acrylamide-co-acrylic Acid/Maleic Acid)-Hydroxyapatite Composite Hydrogel.

BACKGROUND: Hydroxyapatite and its derivatives have been used for a lot of applications. One of them is drug release studies. Due to its low adhesion strength and lack of the strength and durability required for load-carrying applications, there is a need to improve the properties of hydroxyapatite. For this aim, the most important factors are increasing pH sensitivity and preventing coagulation. Mixing it with multifunctional polymers is the best solution. OBJECTIVES: The main objectives are: 1- preparing poly(acrylamide-co-acrylic acid/maleic acid)- hydroxyapatite (PAm-co-PAA/PMA-HApt), 2- assessment of (PAm-co-PAA/PMA-HApt) and dox-loaded poly(acrylamide-co-acrylic acid/maleic acid) (Dox-(PAm-co-PAA/PMA-HApt)) composite hydrogels, and 3- elucidating the difference in behavior of drug release studies between hydroxyapatite (HApt) and poly(acrylamide-co-acrylic acid/maleic acid) composite hydrogels. METHODS: A composite of PAm-co-PAA/PMA-HApt was prepared by direct polymerization of acrylamide-co-acrylic acid/maleic acid in a suspension of HApt. The drug loading and release features of PAm-co-PAA/PMA-HApt and HApt were then investigated for doxorubicin (dox) release. Using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TG/DTA), this unique composite hydrogel has been physicochemically investigated. Also, a colorimetric assay was used to assess the in vitro biocompatible support and anticancer activity of HApt and the newly developed composite hydrogel XTT (2,3-Bis-(2-Methoxy-4-Nitro-5-Sulfophenyl)-2H-Tetrazolium-5-Carboxanilide) assay. RESULTS: According to the results of drug release studies of this new material, it is pH sensitive, and PAm-co-PAA/PMA-HApt demonstrated a faster release than HApt at 37°C in the acidic solution of pH 4.5 than in the neutral solution of pH 7.4. The XTT assay outcomes also demonstrated the biocompatibility of PAm-co-PAA/PMA-HApt and HApt and the cytotoxic effect of dox-loaded PAm-co-PAA/PMA-HApt. CONCLUSION: It should be inferred that the drug release profile was improved at pH 4.5 by the newly produced pH-sensitive composite hydrogel.

Magnetic chitosan oligomer-sulfonate-stearic acid triple combination as cisplatin carrier for site-specific targeted on MCF-7 cancer cells: Preparation, characterization and in vitro experiments.

In this study, a new amphiphilic target-specific adsorbent, chitosan oligomer-sulfonate-stearic acid triple combination (S-Cho-SA), and magnetic chitosan oligomer-sulfonate-stearic acid triple combination (M-S-Cho-SA) by oleic acid (OA)-modified Fe3 O4 via hydrophobic interaction are fabricated. By modifying the nanoparticle surfaces and having the ability to magnetically allow the target region, these particles attract attention as important particles used in targeting mechanisms in cancer therapy. With magnetic nanoparticles and an external magnetic field, it is possible to transport therapeutic agents to the target site and keep them in the desired effect zone for a longer period of time. These new adsorbents are characterized by scanning electron microscopy (SEM), attenuated total reflection Fourier transform infrared (ATR FT-IR) spectroscopy, nuclear magnetic resonance (NMR), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), and thermogravimetric analysis (TG/DTA). After chemical characterization, it is complexed with cisplatin (CDDP). The magnetic adsorbents were loaded with high efficiency (>50%), and the release experiments exhibited that cisplatin is released more at pH 4.5 compared with pH 7.4 at 37°C. It showed better drug release results under a magnetic field for magnetic adsorbents (36% for pH 4.5 and 3.6% for pH 7.4). The biocompatibility of the prepared adsorbents was demonstrated via the XTT assay in MCF-7 cell lines. The results also exhibited that S-Cho-SA and M-S-Cho-SA were biocompatible, and free cisplatin and cisplatin-complexed adsorbents showed an antiproliferative effect. The results showed that these new cisplatin-loaded (M-S-Cho-SA) nanoparticles are good candidates for thermotherapy in cancer treatment in the future, as they can provide selectivity by site-specific targeting and hold onto an alternative magnetic field due to the magnetic nature of the nanoparticles.

Thiamine alleviates cognitive impairment and epileptogenesis by relieving brain inflammation in PTZ-induced kindling rat model.

OBJECTIVE: Epileptogenesis, the process by which the brain becomes epileptic, is related to neuroinflammation, hyperexcitability cognitive deficits. Evidence suggests that improving brain inflammation can inhibit the epileptogenesis process and help the emergence of new drugs for the treatment of epilepsy. Therefore, the PTZ kindling model of epilepsy was utilized to assess the neuroprotective role of thiamine in epileptogenesis. METHODS: Male rats were exposed to PTZ-induced kindling and pretreated with low thiamine (25 mg/kg) or high thiamine (50 mg/kg). Cyclooxygenase (COX-1 and COX-2), interleukin 1-beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and nuclear factor-κB (NF-κB) concentrations in the brain were analyzed using biochemical assays. Cognitive function was evaluated using the passive avoidance test. RESULTS: Thiamine ameliorated epileptogenesis and enhanced the rats' performance in the passive avoidance test. Also, thiamine significantly decreased the level of neuroinflammatory mediators in the brain induced by PTZ. CONCLUSION: These results provide evidence that thiamine alleviates PTZ-induced neuroinflammation and cognitive impairments.

Wi-Fi decreases melatonin protective effect and increases hippocampal neuronal damage in pentylenetetrazole induced model seizures in rats.

AIM: Epilepsy is a common brain disorder in which the seizures could cause a neuronal loss in the hippocampus. Oxidative stress has an important role in the pathology of epilepsy. Some studies indicate that Wi-Fi increases oxidative stress and suppresses antioxidant systems. The aim of this study is to investigate the effect of Wi-Fi on melatonin anticonvulsive effect and oxidative damage in pentylenetetrazole-induced epileptic seizures in rats. METHODS: In our study, we used 30 male Wistar Albino rats, 230-250 grams of the body weight. The animals were divided into five groups as control, saline (1 ml/kg/day olive oil for 30 days), Wi-Fi (12 h/day for 30 days), melatonin (10 mg/kg/day for 30 days) and melatonin + Wi-Fi (10 mg/kg/day +12 h/day for 30 days). In the thirtieth day, thirty minutes after the last drugs administration at the indicated doses, PTZ in 45 mg/kg was administered to induce epileptic seizure. The animals were observed for 30 min during the seizure stages (according to the Racine Scale) and first myoclonic jerk times (FMJ). Twenty-four hours after PTZ injection, brain tissues were removed for biochemical and histopathological evaluation. The hippocampal Cornu Ammonis (CA) 1, CA3 and DG (dentate gyrus) regions were histopathologically evaluated in terms of a neuronal damage in addition that oxidative stress markers (total antioxidant status (TAS), total oxidant status (TOS) and oxidative stress index (OSI)) were measured in brain tissues. RESULTS: Wi-Fi was not found to affect behavioral changes associated with epilepsy (p > 0.05). However, Wi-Fi reduced anticonvulsive and antioxidant effect of melatonin (p < 0.05). Moreover, Wi-Fi increased neuronal damage in hippocampus (p < 0.05). CONCLUSION: Wi-Fi did not directly affect epileptic seizures. Nevertheless, it inhibits the positive effects of melatonin on epilepsy and it also has negative effects on hippocampal neuronal damage. These effects of Wi-Fi may occur via oxidative pathways.

Production, purification, and characterization of metalloprotease from Candida kefyr 41 PSB.

A thermostable metalloprotease, produced from an environmental strain of Candida kefyr 41 PSB, was purified 16 fold with a 60% yield by cold ethanol precipitation and affinity chromatography (bentonite-acrylamide-cysteine microcomposite). The purified enzyme appeared as a single protein band at 43kDa. Its optimum pH and temperature points were found to be 7.0 and 105°C, respectively. Km and Vmax values of the enzyme were determined to be 3.5mg/mL and 4.4µmolmL-1min-1, 1.65mg/mL and 6.1µmolmL-1min-1, using casein and gelatine as the substrates, respectively. The activity was inhibited by using ethylenediamine tetraacetic acid (EDTA), indicating that the enzyme was a metalloprotease. Stability of the enzyme was investigated by using thermodynamic and kinetic parameters. The thermal inactivation profile of the enzyme conformed to the first order kinetics. The half life of the enzyme at 95, 105, 115, 125 and 135°C was 1310, 610, 220, 150, and 86min, respectively.

Uranium and thorium adsorption from aqueous solution using a novel polyhydroxyethylmethacrylate-pumice composite.

Poly(hydroxyethylmethacrylate-pumice), [P(HEMA-Pum)], composite was synthesized by free radical polymerization in aqueous solution. The adsorptive features of P(HEMA-Pum) composite were investigated for UO2(2+) and Th(4+) using a range of pH, concentration, time (kinetics), temperature (thermodynamics), ionic strength and selectivity, and the related parameters were derived from the obtained results. These results indicated that all adsorbents had high affinity to the uranium and thorium ions. The parameters obtained from Langmuir, Freundlich and Dubinin-Radsushkevich models fit the data well. The values of enthalpy and entropy changes showed that the overall adsorption process was endothermic (ΔH > 0) and increasing entropy (ΔS > 0), and it was spontaneous (ΔG < 0) as expected. The adsorption kinetics following the pseudo-second order model indicated that the rate-controlling step was chemical adsorption that occurred by ion exchange process. Reusability of P(HEMA-Pum) was also investigated, and it was found that the composite could be used at least 5 times.

Production and immobilization of a novel thermoalkalophilic extracellular amylase from bacilli isolate.

A Thermoalkalophilic amylase was produced from an environmental bacterial isolate. The enzyme was then immobilized through its amino groups onto the epoxy rings of magnetic poly glycidyl methacrylate [m-poly (GMA)] beads. The free enzyme was active within a large pH range, between 7 and 12 and displayed the optimum activity at 95°C and pH 10. The immobilization appeared to increase the stability of the enzyme as its bound form showed optimum activity at 105°C and pH 11.0. Kinetic studies demonstrated that immobilized enzyme had higher K(m) and lower V(max) values. The activity of the free and bound enzyme was determined, at 37°C and pH 10.0 and pH 11.0, respectively, in the presence of various organic solvents and detergents (5%, v/v). Results obtained indicated that detergents, sodium dodecyl sulfate (SDS) and TritonX-100, caused six fold increase and that various organic solvents also increased the activity of the amylase.

Adsorptive features of polyacrylamide-apatite composite for Pb2+, UO(2)2+ and Th4+.

Micro-composite of polyacrylamide (PAA) and apatite (Apt) was prepared by direct polymerization of acrylamide in a suspension of Apt and characterized by means of FT-IR, XRD, SEM and BET analysis. The adsorptive features of PAA-Apt and Apt were then investigated for Pb(2+), UO(2)(2+) and Th(4+) in view of dependency on ion concentration, temperature, kinetics, ion selectivity and reusability. Experimentally obtained isotherms were evaluated with reference to Langmuir, Freundlich and Dubinin-Radushkevich (DR) models. Apt in PAA-Apt had higher adsorption capacity (0.81, 1.27 and 0.69 mol kg(-1)) than bare Apt (0.28, 0.41 and 1.33 mol kg(-1)) for Pb(2+) and Th(4+), but not for UO(2)(2+). The affinity to PAA-Apt increased for Pb(2+) and UO(2)(2+) but not changed for Th(4+). The values of enthalpy and entropy changed were positive for all ions for both Apt and PAA-Apt. Free enthalpy change was DeltaG<0. Well compatibility of adsorption kinetics to the pseudo-second-order model predicated that the rate-controlling step was a chemical sorption. This was consistent with the free energy values derived from DR model. The reusability tests for Pb(2+) for five uses proved that the composite was reusable to provide a mean adsorption of 53.2+/-0.7% from 4x10(-3)M Pb(2+) solution and complete recovery of the adsorbed ion was possible (98+/-1%). The results of this investigation suggested that the use of Apt in the micro-composite form with PAA significantly enhanced the adsorptive features of Apt.

Adsorptive features of chitosan entrapped in polyacrylamide hydrogel for Pb2+, UO2(2+), and Th4+.

Chitosan (Ch) was entrapped in polyacrylamide (PAA) by direct polymerization of acrylamide in a suspension of Ch. The adsorptive features of PAA-Ch and Ch were then investigated for Pb2+, UO2(2+), and Th4+ in view of dependency on ion concentration, temperature, and kinetics. Additional considerations were also given to their ion selectivity and reusability. Isotherms were L and H type of Giles classification and evaluated with reference to Langmuir, Freundlich, and Dubinin-Radushkevich (DR) models. PAA-Ch had higher adsorption capacity than Ch for all studied ions so that the sequences were Th4+>Pb2+>UO2(2+) concordantly with their affective ionic charges. The affinity of Ch in PAA increased for Pb2+ and UO2(2+) but did not change for Th4+. The values of enthalpy and entropy changed were positive for all studied ions for both Ch and PAA-Ch. The negative free enthalpy change value indicated that the adsorption process is spontaneous in the sequence of Th4+>or=Pb2+>UO2(2+). Free energy values derived from DR model implied that the sorption process is the ion exchange. Well compatibility of adsorption kinetics to the pseudosecond-order model predicate that the rate-controlling step is a chemical sorption. The study for ion selectivity showed that both Ch and PAA-Ch had the highest affinity to Pb2+. The reusability tests for Ch and PAA-Ch for Pb2+ for five uses showed that complete recovery of the ion was possible. The studied features of PAA-Ch suggest that the material should be considered as a new adsorbent. It is envisaged that the use of Ch in PAA will enhance practicality and effectiveness of Ch in separation and removal procedures.