Bacteria from Infectious Particles to Cell Based Anticancer Targeted Drug Delivery Systems.

Bacterial ghosts (BGs) are empty cell envelopes of nonliving evacuated bacterial cells. They are free from their cytoplasmic contents; however, they sustain their cellular 3D morphology and antigenic structures, counting on bioadhesive properties. Lately, they have been tested as an advanced drug delivery system (DDS) for different materials like DNA, peptides, or drugs, either single components or combinations. Different studies have revealed that, BG DDS were paid the greatest attention in recent years. The current review explores the impact of BGs on the field of drug delivery and drug targeting. BGs have a varied area of applications, including vaccine and tumor therapy. Moreover, the use of BGs, their synthesis, their uniqueness as a delivery system and application principles in cancer are discussed. Furthermore, the safety issues of BGs and stability aspects of using ghost bacteria as delivery systems are discussed. Future perspective efforts that must be followed for this important system to continue to grow are important and promising.

Correction to: Microbial spectrum, antibiotic susceptibility profile, and biofilm formation of diabetic foot infections (2014-18): a retrospective multicenter analysis.

[This corrects the article DOI: 10.1007/s13205-020-02318-x.].

Solubilization, Hansen solubility parameters, and thermodynamic studies of delafloxacin in (transcutol + 1-butyl-3-methyl imidazolium hexafluorophosphate) mixtures.

The solubilization, Hansen solubility parameters (HSPs), and thermodynamic properties of delafloxacin (DLN) in various unique combination of Transcutol-HP® (THP) and 1-butyl-3-methyl imidazolium hexafluorophosphate ionic liquid (BMIM-PF6) mixtures were evaluated for the first time in this research. The 'mole fraction solubilities (x3)' of DLN in different (THP + BMIM-PF6) compositions were determined at 'T = 298.2-318.2 K' and 'p = 0.1 MPa'. The HSPs of DLN, neat THP, neat BMIM-PF6, and binary (THP + BMIM-PF6) compositions free of DLN were also determined. The x3 data of DLN was regressed using 'van't Hoff, Apelblat, Yalkowsky-Roseman, Jouyban-Acree and Jouyban-Acree-van't Hoff models' with overall error values of less than 3.0%. The highest and lowest x3 value of DLN was recorded in neat THP (5.48 × 10-3 at T = 318.2 K) and neat BMIM-PF6 (6.50 × 10-4 at T = 298.2 K), respectively. The solubility of DLN was found to be enhanced significantly with an arise in temperature in all (THP + BMIM-PF6) compositions including pure THP and pure BMIM-PF6. However, there was slight increase in DLN solubility with increase in THP mass fraction in all (THP + BMIM-PF6) mixtures. The HSP of pure THP and pure BMIM-PF6 were found very close to each other, suggesting the great potential of both solvents in DLN solubilization. The maximum solute-solvent interactions at molecular level were recorded in DLN-THP compared to DLN-BMIM-PF6. An 'apparent thermodynamic analysis' study indicated an 'endothermic and entropy-driven dissolution' of DLN in all (THP + BMIM-PF6) compositions including neat THP and BMIM-PF6.

Formulation and in vitro and in vivo evaluation of surfactant-stabilized mucoadhesive nanogels for vaginal delivery of fluconazole.

Surfactant-stabilized mucoadhesive nanogels (NGs) for vaginal delivery of fluconazole (FLZ) were studied and evaluated in this work. FLZ-NG formulations were prepared using two different types of mucoadhesive polymers, Carbopol 934 (Ca934) and Pluronic F-127 (PF127). A rheology study revealed a non-Newtonian pseudoplastic flow behavior (shear thinning) in the prepared NGs. The viscosity of Ca934 NG (0.47 Pa s) was much lower compared to the PF127 NG (6.10 Pa s). The rheology study results correlated well with the in vitro FLZ release profile from the NG formulations. A pH study (pH = 3.90-4.90) revealed that the formulations were physiologically suitable for vaginal application, to avoid the irritation of the vaginal mucosa. Finally, in vitro and in vivo antimicrobial tests were performed. FLZ incorporated into the Ca934 gel had the strongest antimicrobial effect, with a mean inhibition zone of 24 ± 1.6 mm. Based on these results, it was concluded that the mucoadhesive NG incorporating FLZ resulted in a sustained release and enhanced antimicrobial effect, which would enhance and prolong the therapeutic effects of vaginally delivered FLZ.

Microbial spectrum, antibiotic susceptibility profile, and biofilm formation of diabetic foot infections (2014-18): a retrospective multicenter analysis.

This study identifies the risk factors, microbiological properties, antimicrobial susceptibility patterns, mortality, and clinical complications associated with organisms causing diabetic foot infections (DFIs) with or without antibiotic treatment using data from a retrospective multicenter surveillance. Specimens collected from different hospitals were cultured and the extended-spectrum ß-lactamase (ESBL) excretion was estimated. The antibacterial susceptibility pattern and biofilm formation were completed along with the recommended standard methods. Overall, 792 diabetic foot patients (DFPs) were enrolled and a total of 1803 causative organisms were isolated. Polymicrobial infection was identified in 48.5% of the patients. The isolated Gram-positive pathogens (46.7%) were higher than Gram-negative (38.6%) or anaerobes (7.9%). The predominant pathogens were S. aureus (22.2%), methicillin-resistant S. aureus (7.7%), Enterococcus spp. (12.8%), Pseudomonas aeruginosa (9.4%), E. coli (7.9%), Klebsiella spp. (7.5%), Proteus mirabilis (8.9%), coagulase negative staphylococci (CoNS) (6.6%), anaerobic organisms (5.9%), and fungi (2.3%). Vancomycin and clindamycin exhibited no activity against Gram-positive bacteria. However, meropenem and imipenem displayed high activity against the Gram-negative isolates. Out of the 765 tested strains, 251 showed moderate (15.8%) to high (34%) level biofilm-producing phenotype. DFIs were widespread among the diabetic patients with different microbial etiology and the major organisms were aerobic organisms. Our findings may provide an insight into the development of appropriate therapeutic strategies for the management of DFIs.

Bacteriosomes as a Promising Tool in Biomedical Applications: Immunotherapy and Drug Delivery.

Bacteriosomes are a member of cell-derived vesicles that are proposed as promising tools in diagnosis, therapy, and drug delivery. These vesicles could be derived from a virus, bacterial cells, and animal cells. Biotechnology techniques were used in bioengineering of cell-derived vesicles in vitro, and in vivo. Bacterial vesicles such as bacterial cells, bacterial ghost, or bacteriosomes are vesicular structures derived from bacteria produced by manipulation of bacterial cells by chemical agents or gene-mediated lysis. Subsequently, bacterial vesicles (bacteriosomes) are non-living, non-denatured bacterial cell envelopes free of the cytoplasm and genetic materials. Gram-negative and Gram-positive bacteria are exploited in the production of bacteriosomes. Bacteriosomes have instinct organs, tissues, cells, as well as subcellular tropism. Moreover, bacteriosomes might be used as immunotherapy and/or drug delivery shuttles. They could act as cargoes for the delivery of small drugs, large therapeutics, and nanoparticles to the specific location. Furthermore, bacteriosomes have nature endosomal escaping ability, hence they could traffic different bio-membranes by endocytosis mechanisms. Therefore, bacterial-derived vesicles could be used in therapy and development of an innovative drug delivery systems. Consequently, utilizing bacteriosomes as drug cargoes enhances the delivery and efficacy of administered therapeutic agents. This review highlighted bacteriosomes in terms of source, engineering, characterization, applications, and limitations.

Engineering of Exosomes: Steps Towards Green Production of Drug Delivery System.

Targeting of therapeutic agents to their specific site of action not only increases the treatment efficacy, but also reduces systemic toxicity. Therefore, various drug delivery systems (DDSs) have been developed to achieve this target. However, most of those DDSs have several issues regarding biocompatibility and environmental hazard. In contrast to the synthetic DDSs, exosome-based natural carriers are biocompatible, biodegradable and safe for the environment. Since exosomes play a role in intercellular communication, they have been widely utilized as carriers for different therapeutic agents. This article was aimed to provide an overview of exosomes as an environment-friendly DDS in terms of engineering, isolation, characterization, application and limitation.

Bacterial Ghosts Carrying 5-Fluorouracil: A Novel Biological Carrier for Targeting Colorectal Cancer.

Bacterial ghosts (BGs) are non-deformed bacterial cell envelopes that possess undamaged external configurations for precise attachment to different cells of the human body. The Escherichia coli BGs were successfully produced using a modified sponge-like reduced protocol and characterized by SEM. Four different concentrations of 5-fluorouracil (5-FU) were used to study the impact on the "ghosts" cell wall. 5-FU was then loaded into the BGs and the loading capacity (LC %) and entrapment efficiency (EE %) were determined and were found to be 38.3 ± 0.8 and 76.6 ± 0.8, respectively. The in vitro release studies were conducted in dialysis bags over a time period of 16 days and the accumulative 5-FU released (%) was calculated. Overall, 69.2% of the ghost-associated 5-FU was released from the BGs and release from the E. coli ghosts is governed by non-Fickian diffusion. The Caco-2 cell line was used to investigate the cytotoxicity of 5-FU-loaded BGs.

Analysis of anti-neoplastic drug in bacterial ghost matrix, w/o/w double nanoemulsion and w/o nanoemulsion by a validated 'green' liquid chromatographic method.

The objective of the present investigation was to develop and validate a 'green' reversed phase high-performance liquid chromatography (RP-HPLC) method for rapid analysis of a cytotoxic drug 5-fluorouracil (5-FU) in bulk drug, marketed injection, water-in-oil (w/o) nanoemulsion, double water-in-oil-in-water (w/o/w) nanoemulsion and bacterial ghost (BG) matrix. The chromatography study was carried out at room temperature (25±1°C) using an HPLC system with the help of ultraviolet (UV)-visible detector. The chromatographic performance was achieved with a Nucleodur 150mm×4.6mm RP C8 column filled with 5µm filler as a static phase. The mobile phase consisted of ethyl acetate: methanol (7:3% v/v) which was delivered at a flow rate of 1.0mLmin(-1) and the drug was detected in UV mode at 254nm. The developed method was validated in terms of linearity (r(2)=0.998), accuracy (98.19-102.09%), precision (% RSD=0.58-1.17), robustness (% RSD=0.12-0.53) and sensitivity with satisfactory results. The efficiency of the method was demonstrated by the assay of the drug in marketed injection, w/o nanoemulsion, w/o/w nanoemulsion and BG with satisfactory results. The successful resolution of the drug along with its degradation products clearly established the stability-indicating nature of the proposed method. Overall, these results suggested that the proposed analytical method could be effectively applied to the routine analysis of 5-FU in bulk drug, various pharmaceutical dosage forms and BG.