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The aim of this study was to prepare and evaluate mucoadhesive core-shell nanoparticles based on copolymerization of thiolated chitosan coated on poly methyl methacrylate cores as a carrier for oral delivery of docetaxel. Docetaxel-loaded nanoparticles with various concentrations were prepared via a radical emulsion polymerization method using cerium ammonium nitrate as an initiator. The physicochemical properties of the obtained nanoparticles were characterized by: dynamic light-scattering analysis for their mean size, size distribution, and zeta potential; scanning electron microscopy and transmission electron microscopy for surface morphology; and differential scanning calorimetry analysis for confirmation of molecular dispersity of docetaxel in the nanoparticles. Nanoparticles were spherical with mean diameter below 200 nm, polydispersity of below 0.15, and positive zeta potential values. The entrapment efficiency of the nanoparticles was approximately 90%. In vitro release studies showed a sustained release characteristic for 10 days after a burst release at the beginning. Ex vivo studies showed a significant increase in the transportation of docetaxel from intestinal membrane of rat when formulated as nanoparticles. Cellular uptake of nanoparticles was investigated using fluoresceinamine-loaded nanoparticles. Docetaxel nanoparticles showed a high cytotoxicity effect in the Caco-2 and MCF-7 cell lines after 72 hours. It can be concluded that by combining the advantages of both thiolated polymers and colloidal particles, these nanoparticles can be proposed as a drug carrier system for mucosal delivery of hydrophobic drugs.

The aim of this study was to evaluate a nanoparticulate system with mucoadhesion properties composed of a core of polymethyl methacrylate surrounded by a shell of thiolated chitosan (Ch-GSH-pMMA) for enhancing oral bioavailability of docetaxel (DTX), an anticancer drug. DTX-loaded nanoparticles were prepared by emulsion polymerization method using cerium ammonium nitrate as an initiator. Physicochemical properties of the nanoparticles such as particle size, size distribution, morphology, drug loading, and entrapment efficiency were characterized. The pharmacokinetic study was carried out in vivo using wistar rats. The half-life of DTX-loaded NPs was about 9 times longer than oral DTX used as positive control. The oral bioavailability of DTX was increased to 68.9% for DTX-loaded nanoparticles compared to 6.5% for positive control. The nanoparticles showed stronger effect on the reduction of the transepithelial electrical resistance (TEER) of Caco-2 cell monolayer by opening the tight junctions. According to apparent permeability coefficient (P app) results, the DTX-loaded NPs showed more specific permeation across the Caco-2 cell monolayer in comparison to the DTX. In conclusion, the nanoparticles prepared in this study showed promising results for the development of an oral drug delivery system for anticancer drugs.

In this study, a new, simple, and reproducible high-performance liquid chromatographic method was developed for the determination of pioglitazone in human plasma. After liquid-liquid extraction with diethylether, samples were quantitated on a Nova-Pak C8 column using a mixture of acetonitrile-140mM K2HPO4 (40:60, v/v, pH = 4.45) as mobile phase with UV detection at 269 nm. The flow rate was set at 1.4 mL/min. Ethylparaben was used as internal standard and the total run time of analysis was approximately 7 min. The method was linear over the range of 25-1500 ng/mL of pioglitazone in plasma (r2 > 0.999). The within- and between-day precision values were in the range of 2.4-6.8%. The limit of quantitation of the method was 25 ng/mL. The method was successfully used to study the pharmacokinetics of pioglitazone in healthy volunteers.

A simple, rapid and extractive spectrophotometric method was developed for the determination of pioglitazone hydrochloride in pure and pharmaceutical formulations. This method is based on the formation of yellow ion-pair complex between the basic nitrogen of the drug and bromocresol green (BCG) in phthalate buffer of pH 2.4. The formed complexes were extracted with chloroform and measured at 419 nm. The analytical parameters and their effects on the proposed systems are investigated. Beer’s law was obeyed in the range 2.5-14 μg/mL with correlation coefficient ≥ 0.995. The proposed method has been applied successfully for the determination of drug in commercial tablets dosage forms. No significant interference was observed from the excipients commonly used as pharmaceutical aids with the assay procedure. The validity of the proposed method was established by parallel determination against HPLC method and there was no significant difference between these two methods.