Lacramioara Ochiuz

Preparation and characterisation of alendronate-loaded chitosan microparticles obtained through the spray drying technique.

Microparticles of chitosan (CHT) containing alendronate sodium (AL) were prepared in four drug:polymer ratios (1:1, 1:2, 1:4, 1:6) using the spray drying technique. The efficiency of the method was evaluated by determining production yield (about 70 %) and microencapsulation efficiency, which was almost 100 % in the case of all four of the formulations studied. Particles had a mean size of between 3.6 and 4.6 microm, and a near-spherical shape. The formulations with the highest content of AL (drug:polymer ratio 1:1 and 1:2) showed an asymmetrical distribution of particles, which were larger in size, and had a higher proportion of irregular particles than the other formulations. FT-IR analysis revealed an ionic interaction between AL and CHT. Differential scanning calorimetry and thermogravimetric analysis confirmed the microencapsulation of AL and the increased thermal stability of encapsulated AL. The dissolution profiles of AL from CHT microspheres, at pH values of 1.2 and 6.8, showed a delayed release of AL from microspheres, and the dissolution rate was dependent on the pH and the drug:polymer ratio. It can be concluded that spray drying is a suitable technique for preparing AL-loaded CHT microspheres, and that the drug:polymer ratio can be used to control the rate of AL release from microspheres.

Alendronate-Loaded Modified Drug Delivery Lipid Particles Intended for Improved Oral and Topical Administration

The present paper focuses on solid lipid particles (SLPs), described in the literature as the most effective lipid drug delivery systems that have been introduced in the last decades, as they actually combine the advantages of polymeric particles, hydrophilic/lipophilic emulsions and liposomes. In the current study, we present our most recent advances in the preparation of alendronate (AL)-loaded SLPs prepared by hot homogenization and ultrasonication using various ratios of a self-emulsifying lipidic mixture of Compritol 888, Gelucire 44/14, and Cremophor A 25. The prepared AL-loaded SLPs were investigated for their physicochemical, morphological and structural characteristics by dynamic light scattering, differential scanning calorimetry, thermogravimetric and powder X-ray diffraction analysis, infrared spectroscopy, optical and scanning electron microscopy. Entrapment efficacy and actual drug content were assessed by a validated HPLC method. In vitro dissolution tests performed in simulated gastro-intestinal fluids and phosphate buffer solution pH 7.4 revealed a prolonged release of AL of 70 h. Additionally, release kinetics analysis showed that both in simulated gastrointestinal fluids and in phosphate buffer solution, AL is released from SLPs based on equal ratios of lipid excipients following zero-order kinetics, which characterizes prolonged-release drug systems.

Effect of Apitherapy Formulations against Carbon Tetrachloride-Induced Toxicity in Wistar Rats after Three Weeks of Treatment

The human body is exposed nowadays to increasing attacks by toxic compounds in polluted air, industrially processed foods, alcohol and drug consumption that increase liver toxicity, leading to more and more severe cases of hepatic disorders. The present paper aims to evaluate the influence of the apitherapy diet in Wistar rats with carbon tetrachloride-induced hepatotoxicity, by analyzing the biochemical determinations (enzymatic, lipid and protein profiles, coagulation parameters, minerals, blood count parameters, bilirubin levels) and histopathological changes at the level of liver, spleen and pancreas. The experiment was carried out on six groups of male Wistar rats. Hepatic lesions were induced by intraperitoneal injection of carbon tetrachloride (dissolved in paraffin oil, 10% solution). Two mL per 100 g were administered, every 2 days, for 2 weeks. Hepatoprotection was achieved with two apitherapy diet formulations containing honey, pollen, propolis, Apilarnil, with/without royal jelly. Biochemical results reveal that the two apitherapy diet formulations have a positive effect on improving the enzymatic, lipid, and protein profiles, coagulation, mineral and blood count parameters and bilirubin levels. The histopathological results demonstrate the benefits of the two apitherapy diet formulations on reducing toxicity at the level of liver, spleen and pancreas in laboratory animals.

Synergic Effects of Pregabalin-Acetaminophen Combination in Somatic and Visceral Nociceptive Reactivity

Background/Aims: The present study investigates the effects of pregabalin (PGB), acetaminophen (ACET) and tenoxicam (TNX) administration in somatic and visceral nociception, using the tail flick test and the writhing test in mice. Methods: In the tail flick test, the substances were administered orally and the latency time response was recorded 15, 30, 60, 90 and 120 min after administration. In the writhing test, pain responses were scored every 5 min during a 30-min period after intraperitoneal injection of diluted acetic acid. Results: Our study demonstrated that oral administration of the combination PGB-ACET resulted in a stronger increase of latency reaction - statistically significant after 15 min compared to TNX and after 30 min compared to PGB in tail flick test. In the writhing test, the combination PGB-ACET, but also PGB-TNX, resulted in a stronger decrease of writhe numbers - statistically significant compared to the effects of the separate administration of each substance. This decrease was more intense in animals treated with the combination PGB-ACET than with PGB-TNX. Conclusion: These results suggest an antinociceptive activity which may be a consequence of the synergic action of the substances.

Antibacterial effects of metal oxides-containing nanomaterials in dentistry

The development of dental nanomaterials with antibacterial properties represents a new step against antibacterial resistance, but there are concerns regarding the efficacy of the antibacterial effects of nanoparticles when mixing them with other materials or when using them for surface coating materials. The objective of this review article is to summarize the experimental data regarding the antibacterial effects of metal oxide-containing nanomaterials used in dentistry. Titanium dioxide and zinc oxide are the most studied nanoparticles with antimicrobial properties in dentistry. Most of the dental materials (cements, resin composites, mouthwashes, dental implants) containing metal oxide nanoparticles exhibited in vitro antibacterial activities. One study found that zinc oxide nanoparticles incorporated into glass ionomer cement did not promote antibacterial activity against Streptococcus mutans. There are only few comparative data on the antibacterial behavior of different types of nanoparticles in dental materials. Metal oxide nanoparticles are a promising future direction for dental materials with antibacterial properties.

Survival Prediction for Romanian Patients with Pancreatic Cancer

Pancreatic cancer is one of the most lethal malignancies worldwide and in some of the latest statistics ranks fourth in the total number of deaths related to cancer in patients of both genders. Currently, curative treatment is only possible in cases of resectable disease and during the initial stages. Still, although complete surgical resection is the only potential curative approach of this disease, it can only be performed in 10 to 20% of patients, since most individuals present with advanced disease upon diagnosis. Moreover, in the recent decades the development and improvement of surgical techniques have only improved postoperative mortality, without having any significant impact on the survival, with specialized pancreatic surgery centres reporting mortality below 5%. In this way, in the present study conducted on 188 patients from the “St. Spiridon” Clinical Emergency Hospital Iasi, we were interested in determining the survival rates in pancreatic cancer, as well as looking at the staging criteria for adenocarcinoma of the pancreas that follows the tumor/node/metastasis (TNM) system and the correlations between any of these stages and the overall survival. Weibull distribution was used to estimate the overall survival. Reduced survival in pancreatic cancer was found to be within the limits found in the published literature: 41.7% at 1 year, 8.7% at 3 years and 1.9% at 5 years. Still, no significant correlation was found between any of the disease stages and the overall survival.

Inhibition of bcl-2 and cox-2 Protein Expression after Local Application of a New Carmustine-Loaded Clinoptilolite-Based Delivery System in a Chemically Induced Skin Cancer Model in Mice

Our research has focused on in vitro and in vivo evaluations of a new Carmustine (BCNU)-loaded clinoptilolite-based delivery system. Two clinoptilolite ionic forms—hydrogen form (HCLI) and sodium form (NaCLI)—were prepared, allowing a loading degree of about 5–6 mg BCNU/g of zeolite matrix due to the dual porous feature of clinoptilolite. Clinoptilolite-based delivery systems released 35.23% of the load in 12 h for the BCNU@HCLI system and only 10.82% for the BCNU@NaCLI system. The BCNU@HCLI system was chosen to develop gel and cream semisolid dosage forms. The cream (C_BCNU@HCLI) released 29.6% of the loaded BCNU after 12 h in the Nylon synthetic membrane test and 31.6% in the collagen membrane test, higher by comparison to the gel. The new cream was evaluated in vivo in a chemically induced model of skin cancer in mice. Quantitative immunohistochemistry analysis showed stronger inhibition of B-cell lymphoma-2 (bcl-2) and cyclooxygenase 2 (cox-2) protein expression, known markers for cancer survival and aggressiveness, after the treatment with C_BCNU@HCLI by comparison to all the control treatment types, including an off-label magistral formula commercially available Carmustine cream as reference, bringing evidence that a clinoptilolite-based delivery systems could be used as a cancer drug carriers and controlled release systems (skin-targeted topical delivery systems).

Postoperative Biological and Physiological Gastrointestinal Changes afterWhipple Procedure

In the last years there was an increased interest towards the pancreatic cancer, especially considering its growing incidence (rapidly becoming the fifth cause of death by cancer in the developed countries), lack of any sustainable markers and/or risk factors and the chilling fact that almost 95% of the patients with this disorder are presenting to the hospital in the advanced and unresectable stages. Even more, although known and developed for almost 70 years, the surgical approach for the pancreatic cancer is a subject of debate because its efficacy and postoperative biological changes. It is known that the most common surgery in chronic pancreatitis and pancreatic cancer is represented by the Whipple pancreatico duodenectomy. Still, after an extended resection and reconstruction of the upper gastrointestinal tract, it seems that the digestive physiology can be disrupted. In this way, in the present mini-review we will describe some postoperative gastrointestinal biological and physiological changes after Whipple procedure, by mainly focusing on the gastrointestinal motility, bone demineralization, dumping and re-resection, as well as on the affected pancreatic function, postoperative weight loss and remnant pancreatic fibrosis and how the management of this related pathological aspects can be applied in these cases.

Sonochemical Development of Magnetic Nanoporous Therapeutic Systems as Carriers for 5-Fluorouracil

Therapeutic nanosystems based on magnetic mesoporous silica nanoparticles are successfully obtained by a facile, reproducible and time-saving sonochemical method. Hydrophilic citrate-capped magnetite nanoparticles of about 20 nm are firstly prepared by ultrasound-assisted chemical precipitation. Secondly, freshly-dried magnetite nanoparticles are coated with mesoporous silica shell by sonochemically-modified Strober method. The applied procedure provides easily-separable, stable core-shell nanoparticles consisting of superparamagnetic Fe3O4 cores and mesoporous silica shell. SEM micrographs showed that core-shell nanoparticles are smaller than 400 nm, a prerequisite for biomedical applications by intravenous administrations. Further, these sonochemically prepared magnetic nanoparticles are employed as biocompatible matrices to host and deliver 5-fluorouracil, a highly-toxic low-molecular antimetabolite chemotherapeutic drug. For this, drug molecules are confined into unmodified and amino-modified mesopores of the silica shell by adsorption from alcoholic solutions. A detailed study was performed using XRD, N2-sorption measurements, SEM and FTIR spectroscopy with the primary goal of investigating possible structural, textural and morphological modifications aroused after pore-functionalization and drug nanoconfinement. Magnetic behavior of prepared therapeutic nanosystems is visualized using vibrating sample magnetometry (VSM). Finally, the release profile of 5-fluorouracil from the unmodified and amino-modified nanoparticulate magnetic matrices in PBS solution (pH 7.4) is followed by means of liquid chromatographic measurements. The HPLC method used for determination of 5-fluoruracil in releasing media was fully validated in house, in terms of specificity, linearity, precision, LOD and LOQ establishment.