Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Microbiology and Immunology

Bacterial ghosts (BGs) are defined as the bacterial shells of Gram-positive and Gram-negative bacteria that are devoid from internal contents. They are produced either by genetic or chemical means and can have a variety of important applications in drug delivery and vaccination. In this study, a novel protocol was developed for BGs preparation and testing which involves the incubation of Salmonella enterica serovar typhimurium ATCC 13311 with 7% v/v tween 80 for 24 hours followed by one hour incubation with lactic acid (pH 3.6). The method led to the production of perfect BGs, as evidenced by their morphological and structural characterization. Two of the BG applications were examined; targeted delivery system and vaccination. Loading of Salmonellas{u2019} BGs with doxorubicin (DOX) was successfully maximized (loading capacity= 27.5%). In-vitro release study of DOX loaded BGs showed a sustained release expending182 hours and obeying Higuchi kinetics release model. The BG combined DOX showed superior antiproliferative activity (64.5% over 51% death rate compared to free DOX in HepG2 cells). The novel system also showed a three- folds- less proliferative inhibitory concentration (IC50) (1.328 æg/ml) than that of free DOX (3.374 æg/ml). Both (early and late) apoptosis activity were higher in BG combined DOX (99.3%) than in free DOX (72.7%). The subcutaneous vaccines of both BGs and BG-adjuvant showed a significant humoral and cellular immune response in the vaccinated animals

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