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Background Naringin is a promising anti-inflammatory drug against various disorders including ulcerative colitis. However, its oral bioavailability is low (8%) possibly due to cleavage at the upper gut. Consequently, colon targeting would be necessary for drug protection at the upper gut, enhanced oral bioavailability and potentiated cytoprotection against colitis. Methodology This study involved the formulation of compression-coated tablets of naringin employing mixtures of pH-sensitive Eudragit L100-55 (EUD-L100-55) and different time-dependent polymers including ethyl cellulose (EC), sodium alginate (ALG) and sodium carboxymethyl cellulose (SCMC). Drug-polymer interaction during release was assessed using Fourier transform-infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Tablets were evaluated in vitro. Surface morphology of the optimized tablets either before or after exposure to the different release media was examined employing scanning electron microscopy (SEM). Cytoprotection potential of the optimized tablets against indomethacin-induced colitis in rabbits was screened and compared to core tablets through a histopathological examination of colon, measurement of serum perinuclear antineutrophil cytoplasmic antibodies (pANCA) and immunohistochemical localization of tumor necrosis factor-alpha (TNF-α). Results FT-IR and DSC results may indicate drug-polymers interaction during release. Release retardation could be related to polymer swelling that was in the order of SCMC > ALG > EC. SEM examination indicated more porous coats at the buffers relative to the acidic medium. Colon targeting was expected in case of coats of 5% ALG, 5% SCMC and 10% EC (w/w) in combination with EUD-L100-55; thus, they were selected for in vivo evaluation. Effective cytoprotection of selected tablets against indomethacin-induced colitis was indicated by a significant (P

Phenytoin (PHT) is an antiepileptic drug that was reported to exhibit high wound healing activity. Nevertheless, its limited solubility, bioavailability, and inefficient distribution during topical administration limit its use. Therefore, this study aims to develop, characterize nanostructured lipid carriers (NLCs), and evaluate their potential in topical delivery of PHT to improve the drug entrapment efficiency and sustained release. The NLCs were prepared by hot homogenization followed by ultra sonication method using 2

The aim of this study is to develop and characterize self-nanoemulsifying drug delivery system (SNEDDS) of piroxicam in liquid and solid forms to improve its dissolution, absorption and therapeutic efficacy.The generation of liquid SNEDDS (L-SNEDDS) was composed of soybean or coconut oil/Tween 80/Transcutol HP (12/80/8%w/w) and it was selected as the optimized formulation based on the solubility study and pseudo-ternary phase diagram. Optimized L-SNEDDS and liquid supersaturatable SNEDDS (L-sSNEDDS) preparations were then adsorbed onto adsorbents and formulated as directly compressed tablets.The improved drug dissolution rate in the solid supersaturatable preparation (S-sSNEDDS) may be due to the formation of a nanoemulsion and the presence of drug in an amorphous state with hydrogen bond interaction between the drug and SNEDDS components. In vivo pharmacokinetic studies on eight healthy human volunteers showed a significant improvement in the oral bioavailability of piroxicam from S-sSNEDDS (F12) compared with both the pure drug (PP) and its commercial product (FeldeneThe obtained results ratify that S-sSNEDDS is a promising drug delivery system to enhance the oral bioavailability of piroxicam.

The histone deacetylase inhibitor suberoylanilide hydroxamic acid, known as vorinostat, is a promising anticancer drug with a unique mode of action; however, it is plagued by low water solubility, low permeability, and suboptimal pharmacokinetics. In this study, poly(ethylene glycol)‐b‐poly( dl ‐lactic acid) (PEG‐b‐PLA) micelles of vorinostat were developed. Vorinostat's pharmacokinetics in rats was investigated after intravenous (i.v.) (10 mg/kg) and oral (p.o.) (50 mg/kg) micellar administrations and compared with a conventional polyethylene glycol 400 solution and methylcellulose suspension. The micelles increased the aqueous solubility of vorinostat from 0.2 to 8.15 ± 0.60 and 10.24 ± 0.92 mg/mL at drug to nanocarrier ratios of 1:10 and 1:15, respectively. Micelles had nanoscopic mean diameters of 75.67 ± 7.57 and 87.33 ± 8.62 nm for 1:10 and 1:15 micelles, respectively, with drug loading capacities of 9.93 ± 0.21% and 6.91 ± 1.19%, and encapsulation efficiencies of 42.74 ± 1.67% and 73.29 ± 4.78%, respectively. The micelles provided sustained exposure and improved pharmacokinetics characterized by a significant increase in serum half‐life, area under curve, and mean residence time. The micelles reduced vorinostat clearance particularly after i.v. dosing. Thus, PEG‐b‐PLA micelles significantly improved the p.o. and i.v. pharmacokinetics and bioavailability of vorinostat, which warrants further investigation.

Effects of tromethamine (Tris), polyvinylpyrrolidone (PVP-K25), and low molecular weight chitosan (LM-CH) on dissolution and therapeutic efficacy of glimepiride (Gmp) were investigated using physical mixtures (PMs), coground mixtures, coprecipitates (Coppts) or kneaded mixtures (KMs), and compared with drug alone. Fourier transform infrared spectroscopy, differential scanning colorimetry, and X-ray diffractometry were performed to identify any physicochemical interaction with Gmp. Surface morphology was examined via scanning electron microscopy. The results of Gmp in vitro dissolution revealed that it was greatly enhanced by Coppt with Tris or PVP-K25 and KM with LM-CH at a drug to carrier ratio of 1:8. Gmp amorphization by PVP-K25 and LM-CH was a major factor in increasing Gmp dissolution. Being basic, Tris might increase the pH of the microdiffusion layer around Gmp particles improving its dissolution. Formation of water-soluble complexes suggested by solubility study may also explain the enhanced dissolution. Capsules were prepared from Coppts and KM 1:8 drug to carrier binary systems and also with Tris PMs. In vivo, the hypoglycemic efficacy of Gmp capsules in rabbits increased by 1.63-, 1.50-, and 1.46-fold for 1:8 Coppts with Tris or PVP-K25 and KM with LM-CH respectively, compared with Gmp alone. Surprisingly, the response to Tris PM 1:20 capsules was 1.52-fold revealing statistically insignificant difference to that of Tris Coppt 1:8 (1.63 fold). As a conclusion, dissolution enhancement and hypoglycemic potentiation by 1:20 PM of Gmp/Tris, being simple and easy to prepare, may enable development of a reduced-dose and fast-release oral dosage form of Gmp.

The development of injectable hydrogels for protein delivery is a major challenge. In this study, insulin/alpha-cyclodextrin (alpha-CyD) and gamma-CyD polypseudorotaxane (PPRX) hydrogels were prepared through inclusion complexation between high molecular weight poly(ethylene glycol) (PEG) and CyDs. The alpha-CyD and gamma-CyD PPRX hydrogels were formed by inserting one PEG chain in the alpha-CyD cavity and two PEG chains in the gamma-CyD cavity. Insulin/CyD PPRX hydrogel formation was based on physical crosslinking induced by self-assembling without chemical crosslinking reagent. The supramolecular structures of insulin/CyD PPRX hydrogels were confirmed with (1)H nuclear magnetic resonance ((1)H NMR), X-ray diffraction, differential scanning calorimetry (DSC) and scanning electron microscopy (SEM). The in vitro release study showed that the release rate of insulin from the CyDs PPRX hydrogels decreased in the order of gamma-CyD PPRX hydrogel>alpha-CyD PPRX hydrogel. This decrease was controlled by the addition of CyDs to the medium. The serum insulin level after subcutaneous administration of gamma-CyD PPRX hydrogel to rats was significantly prolonged, accompanying with an increase in the area under serum concentration-time curve, which was clearly reflected in the prolonged hypoglycemic effect. In conclusion, these results suggest the potential use of gamma-CyD PPRX hydrogel as an injectable sustained release system for insulin.

Topical application of nuclear factor-kappaB (NF-kappaB) decoy appears to provide a novel therapeutic potency in the treatment of inflammation and atopic dermatitis. However, it is difficult to deliver NF-kappaB decoy oligonucleotides (ODN) into the skin by conventional methods based on passive diffusion because of its hydrophilicity and high molecular weight. In this study, we evaluated the in vitro transdermal delivery of fluorescein isothiocyanate (FITC)-NF-kappaB decoy ODN using a pulse depolarization (PDP) iontophoresis. In vitro iontophoretic experiments were performed on isolated C57BL/6 mice skin using a horizontal diffusion cell. The apparent flux values of FITC-NF-kappaB decoy ODN were enhanced with increasing the current density and NF-kappaB decoy ODN concentration by iontophoresis. Accumulation of FITC-NF-kappaB decoy ODN was observed at the epidermis and upper dermis by iontophoresis. In mouse model of skin inflammation, iontophoretic delivery of NF-kappaB decoy ODN significantly reduced the increase in ear thickness caused by phorbol ester as well as the protein and mRNA expression levels of tumor necrosis factor-alpha (TNF-alpha) in the mice ears. These results suggest that iontophoresis is a useful and promising enhancement technique for transdermal delivery of NF-kappaB decoy ODN.