The rise in bacterial resistance to currently used antibiotics is the main focus of medical researchers. Bacterial multidrug resistance (MDR) is a major threat to humans, as it is linked to greater rates of chronic disease and mortality. Hence, there is an urgent need for developing effective strategies to overcome the bacterial MDR. Metal–organic frameworks (MOFs) are a new class of porous crystalline materials made up of metal ions and organic ligands that can vary their pore size and structure to better encapsulate drug candidates. This study reports the synthesis of ribose-coated Cu-MOFs for enhanced bactericidal activity of chloramphenicol (CHL) against Escherichia coli (resistant and sensitive) and MDR Pseudomonas aeruginosa. The synthesized Cu-MOFs were characterized with DLS, FT-IR, powder X-ray diffraction, scanning electron microscope, and atomic force microscope. They were further investigated for their efficacy against selected bacterial strains. The synthesized ribose-coated Cu-MOFs were observed as spherical shape structure with the particle size of 562.84 ± 13.42 nm. CHL caused the increased inhibition of E. coli and MDR P. aeruginosa with significantly reduced MIC and MBIC values after being encapsulated in ribose-coated Cu-MOFs. The morphological analysis of the bacterial strains treated with ribose-coated CHL-Cu-MOFs showed the complete morphological distortion of both E. coli and MDR P. aeruginosa. Based on the results of the study, it can be suggested that ribose-coated Cu-MOFs may be an effective alternate candidate to overcome the MDR and provide new perspective for the treatment of MDR bacterial infections.

Multiple drug resistant (MDR) has become a major issue in developing countries. MDR bacterial infections lead to significant increase in morbidity, mortality and cost of prolonged treatments. Therefore, designing of strategies for improving the antimicrobial potential of the therapeutic agents are highly required. Metal organic frameworks (MOFs) are highly tunable hybrid material, consist of metal ions linked together by organic bridging ligands have been used as an efficient drug delivery carrier because of their biodegradability, low toxicity and structure integrity upon loading and functionalizing process. Current study was based on the synthesis of chitosan coated MOFs with enhanced contact with S. aureus cell surface. Chitosan is deacetylated derivative of chitin and capable for non-bonding interaction with negatively charged bacterial cell leading to enhanced contact of MOFs with S. aureus. Chitosan coated MOFs were characterized with various techniques such as atomic force microscopy, scanning electron microscopy, DLS, FT-IR, TGA, DSC and Powder X-ray diffraction. They were also studied for their efficacy on resistant S. aureus, results revealed that Vancomycin bactericidal activity significantly increased upon loading in chitosan coated MOFs and caused increased inhibition of resistant S. aureus. AFM analysis of S. aureus strains clearly revealed complete distortion of morphology by treating with chitosan modified drug loaded MOFs. Findings of the current study suggest the potential of chitosan coated MOFs for reversing bacterial resistance against Vancomycin and provide new perspectives for improved antibiotic therapy of infections associated with MDR.

Ceftriaxone sodium cannot be delivered orally due to its lower permeability and gastric instability. Self-nanoemulsifying drug delivery systems (SNEDDS) spontaneously form oil-in-water nanoemulsions and are preferred for oral drug delivery owing to their enhanced permeation capabilities. This study is based on design and development of permeation enhancer containing SNEDDS for oral bioavailability of ceftriaxone sodium. Cinnamon oil, Tween 80 and propylene glycol were selected as oil, surfactant and co-surfactant respectively for the development of SNEDDS on the base of drug solubility and emulsifying ability. Region of self-nanoemulsification was selected through construction of phase diagram. Optimal formulation with best attributes consisted 43.33%, 30% and 26.77% (w/w) oil, surfactant and co-surfactant respectively. SNAC (Sodium N-[8-(2-hydroxybenzoyl)aminolcaprylate) was used as permeation enhancer for the development of SNEDDS. The resultant nano-emulsion was investigated for various parameters and stabilities using zetasizer, atomic force microscope, TGA, DSC, FTIR analysis and dilution and thermodynamic stability studies. It was further screened for cellular uptake and in vivo oral bioavailability of the drug. Drug loaded nano-emulsion revealed negatively charged nano size droplets (166-208 nm) and was highly stable against dilution as well as temperature. Drug remained chemically well intact in solubilized from in oil droplets. The drug cellular uptake and in vivo oral bioavailability remarkably increased upon delivery in permeation enhancer containing SNEDDS. Findings of the study confirm the applicability of the designed SNEDDS for enhancing oral bioavailability of Ceftriaxone sodium. (C) 2019 Elsevier B.V. All rights reserved.