Thermoresponsive bacteriophage nanocarrier as a gene delivery vector targeted to the gastrointestinal tract.

The use of the gastrointestinal tract as a site for the local delivery of DNA is an exciting prospect. In order to obtain an effective vector capable of delivering a gene of interest to target cells to achieve sufficient and sustained transgene expression, with minimal toxicity, we developed a new generation of filamentous bacteriophage. This particular bacteriophage was genetically engineered to display an arginine-glycine-aspartic acid (RGD) motif (an integrin-binding peptide) on the major coat protein pVIII and carry a mammalian DNA cassette. One unanticipated observation is the thermoresponsive behavior of engineered bacteriophage. This finding has led us to simplify the isolation method to purify bacteriophage particles from cell culture supernatant by low-temperature precipitation. Our results showed that, in contrast to non-surface modified, the RGD-modified bacteriophage was successfully used to deliver a transgene to mammalian cells. Our in vitro model of the human intestinal follicle-associated epithelium also demonstrated that bacteriophage particles were stable in simulated gastrointestinal fluids and able to cross the human intestinal barrier. In addition, we confirmed an adjuvant property of the engineered bacteriophage to induce nitric oxide production by macrophages. In conclusion, our study demonstrated the possibility of using bacteriophage for gene transfer in the gastrointestinal tract

Characterization of chitosan acetate as a binder for sustained release tablets

10.1016/j.jconrel.2004.06.008Journal of Controlled Release99115-26JCRE

Characterization of Chitosan Acetate as a Binder for Sustained Release Tablets

Abstract A chitosan derivative as an acetate salt was successfully prepared by using a spray drying technique. Physicochemical characteristics and micromeritic properties of spray-dried chitosan acetate (SD-CSA) were studied as well as drug-polymer and excipient-polymer interaction. SD-CSA was spherical agglomerates with rough surface and less than 75 Am in diameter. The salt was an amorphous solid with slight to moderate hygroscopicity. The results of Fourier transform infrared (FTIR) and solidstate 13 C NMR spectroscopy demonstrated the functional groups of an acetate salt in its molecular structure. DSC and TGA thermograms of SD-CSA as well as FTIR and NMR spectrum of the salt, heated at 120 8C for 12 h, revealed the evidence of the conversion of chitosan acetate molecular structure to N-acetylglucosamine at higher temperature. No interaction of SD-CSA with either drugs (salicylic acid and theophylline) or selected pharmaceutical excipients were observed in the study using DSC method. As a wet granulation binder, SD-CSA gave theophylline granules with good flowability (according to the value of angle of repose, Carr's index, and Hausner ratio) and an excellent compressibility profile comparable to a pharmaceutical binder, PVP K30. In vitro release study of theophylline from the tablets containing 3% w/w SD-CSA as a binder demonstrated sustained drug release in all media. Cumulative drug released in 0.1 N HCl, pH 6.8 phosphate buffer and distilled water was nearly 100% within 6, 16 and 24 h, respectively. It was suggested that the simple incorporation of spray-dried chitosan acetate as a tablet binder could give rise to controlled drug delivery systems exhibiting sustained drug release.

Chitosan and Poly (Vinyl Alcohol) microparticles produced by membrane emulsification for encapsulation and pH controlled release

© 2015 Elsevier B.V. The Dispersion Cell membrane emulsification technique was used for the production of w/o emulsions with controlled droplet size and narrow size distribution. The influence of the operating parameters of the process was investigated. Varying the dispersed phase flux (10-1250 L h-1 m-2) and the shear stress (2-59 Pa), droplets between 30 and 280 μm were produced with CV's as low as 18%. Nickel and stainless steel membranes were used for the membrane emulsification. Pore geometry influenced the droplet size as well as uniformity and a normally hydrophilic stainless steel membrane with sharp pore openings produced more uniform and smaller drops compared to a PTFE coated hydrophobic nickel membrane with a conical pore surface. For the dispersed phase 15 wt.% PVA or 1-3 wt.% chitosan as well as their blends in water were used. Surfactants PGPR and ABIL EM90 were tested to determine their capability to form stable emulsions in Miglyol 840. PGPR could not be used to stabilize the emulsion with chitosan as the dispersed phase, probably due to the chemical interference between the carboxyl group present in the PGPR and chitosan. Solid microparticles were obtained by chemical crosslinking with glutaraldehyde (GA) at different concentrations (1-50 vol.%). Particles crosslinked using less than 10 vol.% GA were able to swell and release encapsulated compounds. Acid sensitive particles were produced by blending the PVA and chitosan. Up to 80% of Cu2+ and 20% of sodium salicylate was released from the particles under acidic conditions. No significant release was determined under neutral conditions