Antibacterial nanotruffles for treatment of intracellular bacterial infection.

Bacterial pathogens residing in host macrophages in intracellular infections are hard to eradicate because traditional antibiotics do not readily enter the cells or get eliminated via efflux pumps. To overcome this challenge, we developed a new particle formulation with a size amenable to selective macrophage uptake, loaded with two antibacterial agents - pexiganan and silver (Ag) nanoparticles. Here, pexiganan was loaded in 600 nm poly(lactic-co-glycolic acid) (PLGA) particles (NP), and the particle surface was modified with an iron-tannic acid supramolecular complex (pTA) that help attach Ag nanoparticles. PLGA particles coated with Ag (NP-pTA-Ag) were taken up by macrophages, but not by non-phagocytic cells, such as fibroblasts, reducing non-specific toxicity associated with Ag nanoparticles. NP-pTA-Ag loaded with pexiganan (Pex@NP-pTA-Ag) showed more potent antibacterial activity against various intracellular pathogens than NP-pTA-Ag or Pex@NP (pexiganan-loaded NP with no Ag), suggesting a collaborative function between pexiganan and Ag nanoparticles. Mouse whole-body imaging demonstrated that, upon intravenous injection, NP-pTA-Ag quickly accumulated in the liver and spleen, where intracellular bacteria tend to reside. These results support that Pex@NP-pTA-Ag is a promising strategy for the treatment of intracellular bacterial infection.

Formulation and evaluation of dried yeast tablets using different techniques.

The aim of this study was to prepare and evaluate dried yeast tablets using both direct compression and dry granulation techniques in comparison with the conventional wet granulation as well as commercial product. Wet granulation technique is not favorable for producing the yeast tablets due to the problems of color darkening and the reduction of the fermentation power of the yeast as a result of the early start of the fermentation process due to the presence of moisture. Twenty six formulae of dried yeast tablets were prepared and evaluated. Certain directly compressible vehicles were employed for preparing these tablets. The quality control tests (weight uniformity, friability, disintegration time and hardness) of the prepared dried yeast tablets were performed according to B.P. 1998 limits. All batches of the prepared tablets complied with the B.P. limits of weight uniformity. Moreover, small values of friability % (1% or less) were obtained for all batches of dried yeast tablets with acceptable hardness values, indicating good mechanical properties which can withstand handling. On the other hand, not all batches complied with the limit of disintegration test which may be attributed to various formulation component variables. Therefore, four disintegrating agents were investigated for their disintegrating effect. It was found that the method of preparation, whether it is direct compression, dry granulation or wet granulation, has an effect on disintegration time of these dried yeast tablets and short disintegration times were obtained for some of the formulae. The shortest disintegration time was obtained with those tablets prepared by direct compression among the other techniques. Therefore, the direct compression is considered the best technique for preparation of dried yeast tablets and the best formula (which showed shorter disintegration time and better organoleptic properties than the available commercial yeast tablets) was chosen. Drug content for dried yeast granular powder, and the chosen best prepared formula, was determined by gas chromatography (GC). It was found that this formula gave the same alcohol content produced by an equal amount of the dried yeast granular powder. This result in conjunction with weight uniformity indicated drug content uniformity of the prepared dried yeast tablets.