A comparison of thiolated and disulfide‐crosslinked polyethylenimine for nonviral gene delivery

Branched polyethylenimine (25 kDa) is thiolated and compared with redox-sensitive crosslinked derivatives. Both polymers thiol contents are assessed; the thiolated polymers have 390–2300 mmol SH groups/mol, whereas the crosslinked polymers have lower thiol contents. Cytotoxicity assays show that both modified polymers give lower hemolysis than unmodified PEI. Increased thiol content increases gene transfer efficiency but also elevates cytotoxicity. Crosslinking improves plasmid DNA condensation and enhances transfection efficiency, but extensive crosslinking overstabilizes the polyplexes and decreases transfection, emphasizing the need to balance polyplex stabilization and unpacking. Thus, at low levels of crosslinking, 25 kDa PEI can be an efficient redox-sensitive carrier system.

Protection of dried probiotic bacteria from bile using bile adsorbent resins

Enteric coated oral tablets or capsules can deliver dried live cells directly into the intestine. Previously, we found that a live attenuated bacterial vaccine acquired sensitivity to intestinal bile when dried, raising the possibility that although gastric acid can be bypassed, significant loss of viability might occur on release from an enteric coated oral formulations. Here we demonstrate that some food-grade lyophilised preparations of Lactobacillus casei and Lactobacillus salivarius also show temporary bile sensitivity that can be rapidly reversed by rehydration. To protect dried bacterial cells from temporary bile sensitivity, we propose using bile acid adsorbing resins, such as cholestyramine, which are bile acid binding agents, historically used to lower cholesterol levels. Vcaps™ HPMC capsules alone provided up to 830-fold protection from bile. The inclusion of 50% w/w cholestyramine in Vcaps™ HPMC capsules resulted in release of up to 1700-fold more live Lactobacillus casei into simulated intestinal fluid containing 1% bile, when compared to dried cells added directly to bile. We conclude that delivery of dried live probiotic organisms to the intestine may be improved by providing protection from bile by addition of bile adsorbing resins and the use of HPMC capsules.

Hydrogen-bonded complexes and blends of poly(acrylic acid) and methylcellulose: nanoparticles and mucoadhesive films for Ocular Delivery of Riboflavin

Poly(acrylic acid) (PAA) and methylcellulose (MC) are able to form hydrogen-bonded interpolymer complexes (IPCs) in aqueous solutions. In this study, the complexation between PAA andMC is explored in dilute aqueous solutions under acidic conditions. The formation of stable nanoparticles is established,whose size and colloidal stability are greatly dependent on solution pH and polymers ratio in the mixture. Poly(acrylic acid) and methylcellulose are also used to prepare polymeric films by casting from aqueous solutions. It is established that uniform films can be prepared by casting from polymer mixture solutions at pH 3.4–4.5. At lower pHs (pH<3.0) the films have inhomogeneous morphology resulting from strong interpolymer complexation and precipitation of polycomplexes, whereas at higher pHs (pH 8.3) the polymers form fully immiscible blends because of the lack of interpolymer hydrogen-bonding. The PAA/MC films cast at pH 4 are shown to be non-irritant to mucosal surfaces. These films provide a platform for ocular formulation of riboflavin, a drug used for corneal crosslinking in the treatment of keratoconus. An in vitro release of riboflavin as well as an in vivo retention of the films on corneal surfaces can be controlled by adjusting PAA/MC ratio in the formulations.

Efficacy of a live attenuated Escherichia coli O78:K80 vaccine in chickens and turkeys

A candidate live vaccine for avian pathogenic Escherichia coli (APEC) was constructed from a virulent field APEC O78 strain by mutation of the aroA gene. The mutant was highly similar to the parent wild-type strain in respect of colony morphology, motility, growth in suspension, hemagglutination, Congo Red binding, HEp-2 cell adhesion, and the elaboration of surface antigens type 1 fimbriae and flagella, although production of curli fimbriae was reduced marginally. The mutant proved avirulent when inoculated into 1-day-old chicks by spray application and when presented again in the drinking water at 7 days of age. Chickens and turkeys vaccinated with an O78 aroA mutant were protected against a challenge at 6 wk of age by virulent APEC strains.

Efficient wireless power delivery for biomedical implants

Power delivery for biomedical implants is a major consideration in their design for both measurement and stimulation. When performed by a wireless technique, transmission efficiency is critically important not only because of the costs associated with any losses but also because of the nature of those losses, for example, excessive heat can be uncomfortable for the individual involved. In this study, a method and means of wireless power transmission suitable for biomedical implants are both discussed and experimentally evaluated. The procedure initiated is comparable in size and simplicity to those methods already employed; however, some of Tesla’s fundamental ideas have been incorporated in order to obtain a significant improvement in efficiency. This study contains a theoretical basis for the approach taken; however, the emphasis here is on practical experimental analysis.

Advances in ophthalmic drug delivery

Various strategies for ocular drug delivery are considered; from basic formulation techniques for improving availability of drugs; viscosity enhancers and mucoadhesives aid drug retention and penetration enhancers promote drug transport into the eye. The use of drug loaded contact lenses and ocular inserts allows drugs to be better placed where they are needed for more direct delivery. Developments in ocular implants gives a means to overcome the physical barriers that traditionally prevented effective treatment. Implant technologies are under development allowing long term drug delivery from a single procedure, these devices allow posterior chamber diseases to be effectively treated. Future developments could bring artificial corneas to eliminate the need for donor tissue and one-off implantable drug depots lasting the patient’s lifetime.

Exploring farmer preferences for contagious bovine pleuropneumonia vaccination: a case study of Narok District, Kenya

Contagious bovine pleuropneumonia (CBPP) is an economically important disease in most of sub-Saharan Africa. A conjoint analysis and ordered probit regression models were used to measure the preferences of farmers for CBPP vaccine and vaccination attributes. This was with regard to inclusion or not of an indicator in the vaccine, vaccine safety, vaccine stability as well as frequency of vaccination, vaccine administration and the nature of vaccination. The analysis was carried out in 190 households in Narok District of Kenya between October and December 2006 using structured questionnaires, 16 attribute profiles and a five-point Likert scale. The factors affecting attribute valuation were shown through a two-way location interaction model. The study also demonstrated the relative importance (RI) of attributes and the compensation value of attribute levels. The attribute coefficient estimates showed that farmers prefer a vaccine that has an indicator, is 100% safe and is administered by the government (p<0.0001). The preferences for the vaccine attributes were consistent with expectations. Preferences for stability, frequency of vaccination and nature of vaccination differed amongst farmers (p>0.05). While inclusion of an indicator in the vaccine was the most important attribute (RI=43.6%), price was the least important (RI=0.5%). Of the 22 household factors considered, 15 affected attribute valuation. The compensation values for a change from non inclusion to inclusion of an indicator, 95-100% safety, 2h to greater than 2h stability and from compulsory to elective vaccination were positive while those for a change from annual to biannual vaccination and from government to private administration were negative. The study concluded that the farmers in Narok District had preferences for specific vaccine and vaccination attributes. These preferences were conditioned by various household characteristics and disease risk factors. On average the farmers would need to be compensated or persuaded to accept biannual and private vaccination against CBPP. There is need for consideration of farmer preferences for vaccine attribute levels during vaccine formulations and farmer preferences for vaccination attribute levels when designing delivery of vaccines.