Poly(ethylene oxide)-block-poly(styrene oxide) (PEO-b-PSO) and PEO-b-poly(butylene oxide) (PEO-b-PBO) of different chain lengths were synthesized and characterized for their self-assembling properties in water by dynamic/static light scattering, spectrofluorimetry, and transmission electron microscopy. The resulting polymeric micelles were evaluated for their ability to solubilize and protect the anticancer drug docetaxel (DCTX) from degradation. The drug release kinetics as well as the cytotoxicity of the loaded micelles were assessed in vitro. All polymers formed micelles with a highly viscous core at low critical association concentrations (10 mg/L). Micelle morphology depended on the nature of the hydrophobic block, with PBO- and PSO-based micelles yielding monodisperse spherical and cylindrical nanosized aggregates, respectively. The maximum solubilization capacity for DCTX ranged from 0.7 to 4.2% and was the highest for PSO micelles exhibiting the longest hydrophobic segment. Despite their high affinity for DCTX, PEO-b-PSO micelles were not able to efficiently protect DCTX against hydrolysis under accelerated stability testing conditions. Only PEO-b-PBO bearing 24 BO units afforded significant protection against degradation. In vitro, DCTX was released slower from the latter micelles, but all formulations possessed a similar cytotoxic effect against PC-3 prostate cancer cells. These data suggest that PEO-b-P(SO/BO) micelles could be used as alternatives to conventional surfactants for the solubilization of taxanes.

Inhibition of c-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic Ab peptides, is an attractive approach for the treatment of Alzheimer’s disease. We designed a c-secretase inhibitor bearing an ascorbic acid moiety which allows a specific delivery of the drug to the brain. Through, on the one hand, Ab peptide production measurements by specific in vitro assays (c-secretase cell free assay and cell based assay on HEK 293 APP transfected cells) and on the other hand through pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent c-secretase inhibitory activity in vitro. From the obtained results, it is expected that drug 2 will be mainly delivered to the CNS with a low diffusion in the peripheral tissues. Consequently the side effects of this c-secretase inhibitor on the immune cells could be reduced.

Naproxen is one of the most potent NSAIDs and plays an important role in the treatment of neurodegenerative diseases. Poor brain delivery of naproxen at therapeutic doses, in addition to its serious gastrointestinal side effects, has prompted research into the development of a specific carrier system that is capable of delivering naproxen to the brain at smaller doses. The purpose of this study was to evaluate two brain-specific carrier systems of naproxen. The first was the dihydropyridine/pyridinium redox system that utilized a lipophilic chemical delivery system coupled to the carboxylic acid group of naproxen through an ethanolamine linker. Secondly, an ascorbic acid system, which has reducing properties and acts as a biological carrier through sodiumdependent vitamin-C transporter, was used for brain-specific delivery of naproxen. The prepared prodrugs were stable in aqueous buffers (pH 1.2 and 7.4) and rapidly hydrolyzed in biological fluids. Bioavailability studies revealed that both prodrugs 10 and 17 were rapidly cleared from blood with half lives of about 1 h, which will likely decrease systemic adverse effects. The rapid clearance from the blood was accompanied by an increase in the prodrug concentration in the brain, which occurred as a result of the prodrug being more locked in compared to the parent drug naproxen.

The present study aimed to formulate orodispersible tablets of flutamide (FTM) to increase its bioavailability. Orodispersible tablets were prepared by direct compression technique using three different approaches namely; super-disintegration, effervescence and sublimation. Different combined approaches were proposed and evaluated to optimize tablet characteristics. Sodium starch glycolate (SSG) was used as the superdisintegrant. The prepared powder mixtures were subjected to both pre and post compression evaluation parameters including; IR spectroscopy, micromeritics properties, tablet hardness, friability, wetting time, disintegration time and in-vitro drug release. IR studies indicated that there was no interaction between the drug and the excipients used except Ludipress. The results of micromeritics studies revealed that all formulations were of acceptable to good flowability. Tablet hardness and friability indicated good mechanical strength. Wetting and dispersion times decreased from 46 to 38 s by increasing the SSG concentration from 3.33 to 6.66% w/w in tablets prepared by superdisintegration method. The F8 formulation which was prepared by combined approaches of effervescence and superdisintegrant addition gave promising results for tablet disintegration and wetting times but failed to give faster dissolution rate. The incorporation of 1:5 solid dispersion of FTM: PEG6000 instead of the pure drug in the same formulation increased the drug release rate from 73.12 to 96.99% after 15 min. This increase in the dissolution rate may be due to the amorphization of the drug during the solid dispersion preparation. The presence of the amorphous form of the drug was shown in the IR spectra.

The aim of the study was to design and evaluate mucoadhesive buccal patches of naproxen for local treatment of pain and inflammations of the oral cavity. Buccal patches were fabricated by solvent casting technique using hydroxypropylmethylcellulose E4M, Eudragit RLPO, ethyl cellulose, polyvinylpyrrolidone, methyl cellulose, hydroxypropylcellulose and chitosan either alone or as mixtures. Ten formulations were subjected to various evaluation parameters. Based on the evaluation of the results, it was concluded that Formula-2 (F-2) containing 1% HPMC and 0.5% Eudragit RLPO showed good mucoadhesive strength (47.07 g), promising controlled and complete drug release within 210 min, highest residence time (120 min in vivo and 125 min in vitro), acceptable elasticity (13.834 %mm-2), swelling index (85.4% in 15 min) and surface pH (6.5). Accordingly, F-2 could be selected as the best formula among the formulations studied and was subject to further in vivo study. The obtained in vivo results indicate that the concentration of naproxen in the oral cavity was maintained above 4 μg/mL for a period of 120 min, which was within and higher than the reported range of the IC50 of naproxen. A significant in vitro/in vivo correlation was obtained (R2 = 0.9787). The results indicate that the mucoadhesive buccal patches of naproxen may be a good choice to bypass the undesirable systemic side effects and can be proposed as a new therapeutic tool against dental and buccal inflammatory diseases and disturbs.

The aim of the study was to design and evaluate mucoadhesive buccal patches of naproxen for local treatment of pain and inflammations of the oral cavity. Buccal patches were fabricated by solvent casting technique using hydroxypropylmethylcellulose E4M, Eudragit RLPO, ethyl cellulose, polyvinylpyrrolidone, methyl cellulose, hydroxypropylcellulose and chitosan either alone or as mixtures. Ten formulations were subjected to various evaluation parameters. Based on the evaluation of the results, it was concluded that Formula-2 (F-2) containing 1% HPMC and 0.5% Eudragit RLPO showed good mucoadhesive strength (47.07 g), promising controlled and complete drug release within 210 min, highest residence time (120 min in vivo and 125 min in vitro), acceptable elasticity (13.834 %mm-2), swelling index (85.4% in 15 min) and surface pH (6.5). Accordingly, F-2 could be selected as the best formula among the formulations studied and was subject to further in vivo study. The obtained in vivo results indicate that the concentration of naproxen in the oral cavity was maintained above 4 μg/mL for a period of 120 min, which was within and higher than the reported range of the IC50 of naproxen. A significant in vitro/in vivo correlation was obtained (R2 = 0.9787). The results indicate that the mucoadhesive buccal patches of naproxen may be a good choice to bypass the undesirable systemic side effects and can be proposed as a new therapeutic tool against dental and buccal inflammatory diseases and disturbs.