Simple, sensitive and precise spectrophotometric and chromatographic methods were developed for simultaneous determination of Sodium cromoglicate (SCG) and Xylometazoline hydrochloride (XYLO) in their pure form and nasal solution. By applying the spectrophotometric methods, (SCG) was determined by direct spectrophotometry through measuring its zero-order (D0) absorption spectra at 325 nm; while (XYLO)was determined using two methods. The first method utilized the first derivative spectra D1 of (XYLO) after prior separation of SCG from medium using 0.1 N HCl. The second method depends on derivative compensation ratio technique depending on the mean ratio of D1 peak amplitudes of SCG (D231.4 / D309.4). The chromatographic method utilized a Zorbax SB-C18 column and a mobile phase of acetonitrile: 10 mM phosphate buffer (pH 4): triethylamine, in ratio (80: 19.9: 0.1 v/v/v), delivered at flow rate of 1.2 mL/min and the detections were done at 220 nm. The proposed methods were validated in compliance with the ICH guidelines and were successfully applied for the analysis of (SCG) and (XYLO) in the laboratory prepared mixtures and combined pharmaceutical dosage form.

Oral mucositis is one of the main complications of non-surgical cancer treatments. The present work focuses on the treatment or reduction of oral mucositis by using combined mechanism by formation of physical barrier by forming a film to cover the oral ulcer and use of therapeutic agents, such as diclofenac sodium and ofloxacin separately or in combination. The selected polymers for film forming gel formulations are Hydroxypropylcellulose (HPC), hydroxypropyl methylcellulose (HPMC), sodium carboxymethylcellulose (Na CMC) and carbopol 940 (CP). The residence time in simulated buccal saliva was between 5.5 to 6 hours for all formulations. The in-vitro release data of the investigated drugs from the prepared formulations followed zero-order and diffusion mechanism. The permeability studies data revealed that diclofenac sodium showed higher permeability from Na CMC/CP (2:0.3%) than from HPMC 4%, while in case of ofloxacin higher permeability was shown from Na CMC/CP (2:0.3%) than from HPMC/HPC (2:3%). The permeation parameters for diclofenac sodium and ofloxacin in their combination do not depend on either viscosity or pH, they depend on the type of polymers used.

MH, a semisynthetic tetracycline antibiotic with promising neuroprotective properties, was encapsulated into PIC micelles of CMD-PEG as a potential new formulation of MH for the treatment of neuroinflammatory diseases. PIC micelles were prepared by mixing solutions of a Ca2+/MH chelate and CMD-PEG copolymer in a Tris-HCl buffer. Light scattering and 1H NMR studies confirmed that Ca2+/MH/CMD-PEG core-corona micelles form at charge neutrality having a hydrodynamic radius 100 nm and incorporating 50 wt.-% MH. MH entrapment in the micelles core sustained its release for up to 24 h under physiological conditions. The micelles protected the drug against degradation in aqueous solutions at room temperature and at 37°C in the presence of FBS. The micelles were stable in aqueous solution for up to one month, after freeze drying and in the presence of FBS and BSA. CMD-PEG copolymers did not induce cytotoxicity in human hepatocytes and murine microglia (N9) in concentrations as high as 15 mg.mL1 after incubation for 24 h. MH micelles were able to reduce the inflammation in murine microglia (N9) activated by LPS. These results strongly suggest that MH PIC micelles can be useful in the treatment of neuroinflammatory disorders.

We report a nanocarrier based on A2B type miktoarm polymers (A = polyethylene glycol (PEG); B = polycaprolactone (PCL)) for nimodipine (NIM), a hydrophobic drug with very poor aqueous solubility that is commonly prescribed for the prevention and treatment of delayed ischemic neurological disorders. The A2B star polymers were constructed on a core with orthogonal functionalities that facilitated the performance of “click” chemistry followed by ring-opening polymerization. These star polymers assemble into spherical micelles into which NIM can be easily loaded by the co-solvent evaporation method. The micelles obtained from the star polymer PEG7752-PCL5800 showed NIM encapsulation efficiency of up to 78 wt% at a feed weight ratio of 5.0%. The loading efficiency of the micelles was dependent on the length of the PCL arm in the A2B miktoarm polymers. Aqueous solubility of NIM was increased by ~200 fold via micellar encapsulation. The in vitro release of NIM from the micelles was found to occur at a much slower rate than from its solution. Lipopolysaccharide induced nitric oxide production in N9 microglia cells was reduced in the presence of micelle-encapsulated NIM, as well as in the presence of micelles alone. The treatment of microglia with micelle-encapsulated NIM reduced the release of TNF-, a pro-inflammatory cytokine. These results suggest that NIM-loaded miktoarm micelles could be useful in the treatment of neuroinflammation.

Experimental solubilities of budesonide, hydrocortisone, and prednisolone in ethanol + water mixtures at 298.2 K are reported. The solubility of drugs was increased with the addition of ethanol and reached the maximum values of the volume fractions of 90%, 80%, and 80% of ethanol. The Jouyban-Acree model was used to fit the experimental data, and the solubilities were reproduced using previously trained versions of the Jouyban-Acree model and the solubility data in monosolvents in which the overall mean relative deviations (OMRDs) of the models were 5.1%, 6.4%, 37.7%, and 35.9%, respectively, for the fitted model, the trained version for ethanol + water mixtures, and generally trained versions for various organic solvents + water mixtures. Solubilities were also predicted by a previously established log-linear model of Yalkowsky with the OMRD of 53.8 %.

In this study, novel pH-responsive polyion complex micelles (PICMs) were developed for the efficient delivery of nucleic acid drugs, such as antisense oligonucleotide (AON) and short interfering RNA (siRNA). The PICMs consisted of a poly(amidoamine) (PAMAM) dendrimer–nucleic acid core and a detachable poly(ethylene glycol)-block-poly(propyl methacrylate-co-methacrylic acid) (PEG-b-P(PrMA-co-MAA)) shell. The micelles displayed a mean hydrodynamic diameter ranging from 50 to 70 nm, a narrow size distribution, and a nearly neutral surface charge. They could be lyophilized without any additives and stored in dried form. Upon redispersion in water, no change in complexation efficiency or colloidal properties was observed. Entry of the micelles into cancers cells was mediated by a monoclonal antibody fragment positioned at the extremity of the PEG segment via a disulfide linkage. Upon cellular uptake and protonation of the MAA units in the acidic endosomal environment, the micelles lost their corona, thereby exposing their positively charged endosomolytic PAMAM/nucleic acid core. When these pH-responsive targeted PICMs were loaded with AON or siRNAs that targeted the oncoprotein Bcl-2, they exhibited a greater transfection activity than nontargeted PICMs or commercial PAMAM dendrimers. Moreover, their nonspecific cytotoxicity was lower than that of PAMAM. The pH-responsive PICMs reported here appear as promising carriers for the delivery of nucleic acids.

Efficient targeting of DNA to the nucleus is a prerequisite for effective gene therapy. The gene-delivery vehicle must penetrate through the plasma membrane, and the DNA-impermeable double-membraned nuclear envelope, and deposit its DNA cargo in a form ready for transcription. Here we introduce a concept for overcoming intracellular membrane barriers that involves step-wise membrane fusion. To achieve this, a nanotechnology was developed that creates a multi-layered nanoparticle, which we refer to as a Tetra-lamellar Multi-functional Envelope-type Nano Device (T-MEND). The critical structural elements of the T-MEND are a DNA-polycation condensed core coated with two nuclear membrane-fusogenic inner envelopes and two endosome-fusogenic outer envelopes, which are shed in stepwise fashion. A double-lamellar membrane structure is required for nuclear delivery via the stepwise fusion of double layered nuclear membrane structure. Intracellular membrane fusions to endosomes and nuclear membranes were verified by spectral imaging of fluorescence resonance energy transfer (FRET) between donor and acceptor fluorophores that had been dually labeled on the liposome surface. Coating the core with the minimum number of nucleus-fusogenic lipid envelopes (i.e., 2) is essential to facilitate transcription. As a result, the T-MEND achieves dramatic levels of transgene expression in non-dividing cells.

An octaarginine-modified multifunctional envelope-type nano device (R8-MEND) was previously reported to be an efficient nonviral vector for the delivery of plasmid DNA, in vitro and after topical administration. We report herein on a novel stearylated derivative of the INF7 peptide, a derivative of the N-terminal domain of the HA2 protein of the influenza virus envelope, which enhances the endosomal escape of R8-MEND through a mechanism independent of fusion between the MEND coat and the endosomal membrane. The use of the novel peptide derivative would permit the gene expression of the R8-MEND to be improved, both in vitro and in vivo. R8-MEND modified with stearylated INF7 resulted in gene expression levels that were 77-fold higher than unmodified and 20-fold higher than the free INF7 peptide-modified R8-MEND with no cellular toxicity. Spectral imaging in live cells confirmed that the stearylated INF7 modification did not mediate fusion between liposomes and the endosomal membrane. The inclusion of DOPE to the R8-MEND coat was synergistic with the peptide in improving gene transfection. The intravenous injection of an R8-MEND modified with stearylated INF7 to ICR mice resulted in luciferase expression levels 240-fold higher in liver and 115-fold higher in spleen than that of the R8-MEND.

Chromatographic fractionation of the alcoholic extract of the dried fronds of Adiantum capillus-veneris L. (Adiantaceae) yielded seven compounds: Four triterpenoidal compounds belonging to adiantane and filicane groups were isolated from the hexane fraction and identified as isoadiantone (1); isoadiantol-B (2); 3-methoxy-4-hydroxyfilicane (3) and 3,4-dihydroxyfilicane (4) and three flavonoids were isolated from the ethyl acetate fraction and identified as: quercetin (5), quercetin-3-O-glucoside (6) and quercetin-3-O-rutinoside (rutin) (7). The identification of the isolated compounds has been established through their physical, chemical and spectroscopic methods including IR, 1H-NMR, 13C-NMR, HSQC, HMBC, NOESY and MS. Biological studies of the total alcoholic extract, hexane fraction and some of the isolated compounds showed an anti-inflammatory activity while the hypoglycemic study of the total alcoholic extract showed a significant activity.

Chromatographic fractionation of the alcoholic extract of the dried fronds of Adiantum capillus-veneris L. (Adiantaceae) yielded seven compounds: Four triterpenoidal compounds belonging to adiantane and filicane groups were isolated from the hexane fraction and identified as isoadiantone (1); isoadiantol-B (2); 3-methoxy-4-hydroxyfilicane (3) and 3,4-dihydroxyfilicane (4) and three flavonoids were isolated from the ethyl acetate fraction and identified as: quercetin (5), quercetin-3-O-glucoside (6) and quercetin-3-O-rutinoside (rutin) (7). The identification of the isolated compounds has been established through their physical, chemical and spectroscopic methods including IR, 1H-NMR, 13C-NMR, HSQC, HMBC, NOESY and MS. Biological studies of the total alcoholic extract, hexane fraction and some of the isolated compounds showed an anti-inflammatory activity while the hypoglycemic study of the total alcoholic extract showed a significant activity.