Improvement of doxorubicin radioiodination and in-vivo cancer suppression via loading in nanosilver system.

This study aimed at improving the radioiodination of doxorubicin (DOX) and its localization in cancer cell for theranostic purposes. To achieve this goal, a composite of DOX with polyvinyl pyrrolidone (PVP) and silver nanoparticles (AgNPs) was prepared. Both DOX and (DOX/PVP/AgNPs) were radiolabelled with iodine-125 [125I] and optimized using iodogen as a preferable oxidizing agent. The maximum obtained radiochemical yields for both systems were 79.9% and 96.6%, respectively. Interestingly, the biodistribution study revealed that [125I]DOX/PVP/AgNPs had an effective localization on tumors. Moreover, Target/control target (T/CT) ratio of [125I] DOX/PVP/AgNPs showed the highest value of 9.1 at 1 h post injection, suggesting that [125I]DOX/PVP/AgNPs has a great potential as a proposed tumor targeting agent.

Development and optimization of cosolvent-based blended Sertraline orodispersible films - A step to personalized medicine

Abstract Personalized medicine is gaining importance in pharmacotherapeutics as it allows tailoring the drug treatment to achieve the best patient response. Orodispersible film (ODF) is easy to formulate in hospitals, produces dose flexibility to suit an individual needs, particularly for patients suffer from swallowing issues or prohibited to take fluids. Sertraline Hydrochloride (SRT) was solubilized in several cosolvents, then different SRT ODFs based on five hydrophilic polymers namely; polyvinyl alcohol (PVA), hydroxylethyl cellulose (HEC), hydroxypropyl methylcellulose E5 LV (HPMC E5 LV), sodium alginate (NaAlg) and gelatin at two concentrations (2% and 4%) were developed and characterized. The outcomes were exposed to response surface analysis to obtain the desirability results to obtain the optimized formulation. Blended ODFs were developed from 4% PVA and 2% HEC in different blends and then potassium chloride (KCl) as a pore-forming agent was added to the best formulation to investigate its dissolution enhancement effect. F14 containing 4% PVA: 2% HEC 2:1 with 5% KCl showed best physicochemical properties of suitable pH (5.6), disintegration time (6 sec), good folding endurance which released 91 % SRT after 15 min. SRT ODF is an encouraging delivery system in the course of personalized medicine for the management of depression.

Effect of casting solvent, film-forming agent and solubilizer on orodispersible films of a polymorphic poorly soluble drug: an in vitro/in silico study.

In the current work, a full factorial experimental design was utilized to formulate piroxicam into orodispersible films while investigating the effects of some formulation factors on the properties of the resulting films. These factors were (A) the casting solvent: water and acetone/water mixture; (B) the film-forming agent: HPMC K4M and Na-alginate; (C) the solubilization system: no solubilizer, L-arginine, poloxamer and L-arginine/poloxamer mixture. Sixteen formulation runs were prepared by solvent casting method to obtain 10 mg piroxicam dosage units. Drug particle size in the prepared formulations and dissolution efficiency at 30 min were selected as responses variables. Additionally, the prepared films from each formulation were evaluated for other characters as drug content, thickness, residual water…etc. A selected formulation was then evaluated for its in vivo disintegration, palatability and stability. Utilizing acetone in the casting solution, Na-alginate as film-forming agent or both of them resulted in formation of films with larger drug particles and slower dissolution. Combined use of L-arginine and poloxamer showed better drug dissolution than using each alone. HPMC was more favorable than Na-alginate regarding mechanical properties and moisture absorption. Films from the selected formulation showed fast in vivo disintegration and acceptable palatability. These films were stable for 6 months under accelerated storage conditions. According to the computer simulation using GastroPlus™, the in vitro/in vivo behavior of piroxicam in the tested formulation was similar to that of an immediate-release formulation containing BCS class I drug. The selected formulation is therefore would satisfy the WHO perquisites for applying the biowaiver.

Iron oxide nanoparticulate system as a cornerstone in the effective delivery of Tc-99 m radionuclide: a potential molecular imaging probe for tumor diagnosis.

BACKGROUND: The evolution of nanoparticles has gained prominence as platforms for developing diagnostic and/or therapeutic radiotracers. This study aims to develop a novel technique for fabricating a tumor diagnostic probe based on iron oxide nanoparticles excluding the utilization of chelating ligands. METHODS: Tc-99 m radionuclide was loaded into magnetic iron oxide nanoparticles platform (MIONPs) by sonication. 99mTc-encapsulated MIONPs were fully characterized concerning particles size, charge, radiochemical purity, encapsulation efficiency, in-vitro stability and cytotoxicity. These merits were biologically evaluated in normal and solid tumor bearing mice via different delivery approaches. RESULTS: 99mTc-encapsulated MIONPs probe was synthesized with average particle size 24.08 ± 7.9 nm, hydrodynamic size 52 nm, zeta potential -28 mV, radiolabeling yield 96 ± 0.83%, high in-vitro physiological stability, and appropriate cytotoxicity behavior. The in-vivo evaluation in solid tumor bearing mice revealed that the maximum tumor radioactivity accumulation (25.39 ± 0.57, 36.40 ± 0.59 and 72.61 ± 0.82%ID/g) was accomplished at 60, 60 and 30 min p.i. for intravenous, intravenous with physical magnet targeting and intratumoral delivery, respectively. The optimum T/NT ratios of 57.70, 65.00 and 87.48 were demonstrated at 60 min post I.V., I.V. with physical magnet targeting and I.T. delivery, respectively. These chemical and biological characteristics of our prepared nano-probe demonstrate highly advanced merits over the previously reported chelator mediated radiolabeled nano-formulations which reported maximum tumor uptakes in the scope of 3.65 ± 0.19 to 16.21 ± 2.56%ID/g. CONCLUSION: Stabilized encapsulation of 99mTc radionuclide into MIONPs elucidates a novel strategy for developing an advanced nano-sized radiopharmaceutical for tumor diagnosis. Graphical abstract 99mTc-encapsulated MIONPs nanosized-radiopharmaceutical as molecular imaging probe for tumor diagnosis.

Effect of multiple access tracts during percutaneous nephrolithotomy on renal function: evaluation of risk factors for renal function deterioration.

PURPOSE: To assess the impact of multiple access tracts during percutaneous nephrolithotomy (PCNL) on short- and midterm renal function, and to determine risk factors predicting renal function deterioration and/or recoverability. PATIENTS AND METHODS: Patients undergoing PCNL with multiple punctures were prospectively enrolled. Preoperative evaluation included dimercaptosuccinic acid and diethylenetriaminepentaacetic acid renography. Patients were classified according to baseline renal function into patients with normal (<1.4 mg/dL) serum creatinine (group A) and patients with elevated (≥1.4 mg/dL) serum creatinine (group B). Patients were followed with serial serum creatinine evaluations and a repeated renography at 12 months. Factors evaluated for possible impact on renal function changes included preoperative renal function, number of access tracts, hypertension, and diabetes mellitus. RESULTS: There were 102 patients 21 to 65 (mean 39.9) years who completed the study. Fifty patients (group A) had normal preoperative serum creatinine levels and glomerular filtration rate (GFR), which showed no statistically significant change 12 months after PCNL. Fifty-two patients had baseline renal impairment (group B), and they experienced statistically significant worsening of the serum creatinine level and GFR at 12 months postoperatively (P<0.001). Ten (19.23%) patients in group B had a significant deterioration of GFR more than 25%. Independent risk factors for this poor outcome were elevated (≥1.4 mg/dL) preoperative serum creatinine level, diabetes, and hypertension. CONCLUSION: PCNL with multiple tracts carries a risk of adversely affecting renal function. Preoperative baseline renal impairment, diabetes, and hypertension are risk factors for significant renal function deterioration after the procedure.

Influence of some formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres.

The aim of this work was to understand the influence of different formulation variables on the optimization of pH-dependent, colon-targeted, sustained-release mesalamine microspheres prepared by O/O emulsion solvent evaporation method, employing pH-dependent Eudragit S and hydrophobic pH-independent ethylcellulose polymers. Formulation variables studied included concentration of Eudragit S in the internal phase and the ratios between; internal to external phase, drug to Eudragit S and Eudragit S to ethylcellulose to mesalamine. Prepared microspheres were evaluated by carrying out in vitro release studies and determination of particle size, production yield, and encapsulation efficiency. In addition, morphology of microspheres was examined using optical and scanning electron microscopy. Emulsion solvent evaporation method was found to be sensitive to the studied formulation variables. Particle size and encapsulation efficiency increased by increasing Eudragit S concentration in the internal phase, ratio of internal to external phase, and ratio of Eudragit S to the drug. Employing Eudragit S alone in preparation of the microspheres is only successful in forming acid-resistant microspheres with pulsatile release pattern at high pH. Eudragit S and ethylcellulose blend microspheres were able to control release under acidic condition and to extend drug release at high pH. The stability studies carried out at 40°C/75% RH for 6 months proved the stability of the optimized formulation. From the results of this investigation, microencapsulation of mesalamine in microspheres using blend of Eudragit S and ethylcellulose could constitute a promising approach for site-specific and controlled delivery of drug in colon.