PEGylated ofloxacin nanoparticles render strong antibacterial activity against many clinically important human pathogens

Abstract

The rise of bacterial resistance against important drugs threatens their clinical utility. Fluoroquinones, one of the most important classes of contemporary antibiotics has also reported to suffer bacterial resistance. Since the general mechanism of bacterial resistance against fluoroquinone antibiotics (e.g. ofloxacin) consists of target mutations resulting in reduced membrane permeability and increased efflux by the bacteria, strategies that could increase bacterial uptake and reduce efflux of the drug would provide effective treatment. In the present study, we have compared the efficiencies of ofloxacin delivered in the form of free drug (OFX) and as nanoparticles on bacterial uptake and antibacterial activity. Although both poly(lactic-co-glycolic acid) (OFX-PLGA) and methoxy poly(ethylene glycol)-b-poly(lactic-co-glycolic acid) (OFX-mPEG-PLGA) nanoformulations presented improved bacterial uptake and antibacterial activity against all the tested human bacterial pathogens, namely, Escherichia coli, Proteus vulgaris, Salmonella typhimurium, Pseudomonas aeruginosa, Klebsiella pneumoniae and Staphylococcus aureus, OFX-mPEG-PLGA showed significantly higher bacterial uptake and antibacterial activity compared to OFX-PLGA. We have also found that mPEG-PLGA nanoencapsulation could significantly inhibit Bacillus subtilis resistance development against OFX.

Antibacterial activity of complex of enrofloxacin with nanopolymer GluLa-DPG-PEG600

“…It is known that polyethylene glycol can cause membranes permeabilization by increasing the number of pores which probably can increase cell absorption of enrofloxacin in complex with nanopolymer [2]. In addition, scientific article described that PEGylated ofloxacin nanoparticles render strong antibacterial activity against many clinically important human pathogens, which is also explained that polyethylene glycol has the ability to bind DNA and probably enhance the antibiotic activity of complex of enrofloxacin with GluLa-DPG-PEG600 by increasing the affinity of enrofloxacin to DNA [9]. Enrofloxacin belongs to fluoroquinolone class of antibiotics that are effective against both Gram-negative and Gram-positive bacteria, acts via violate DNA synthesis by inhibiting DNA gyrase and topoisomerase II enzymes.…”

Modifications of quinolones and fluoroquinolones: hybrid compounds and dual-action molecules

“…A different approach was used by Marslin and coworkers [30]. They used nanoparticles made of two different polymers, namely, poly( d , l -lactic- co -glycolic acid (PLGA) and methoxy poly(ethylene glycol)-b-poly(lactic- co -glycolic acid) (mPEG–PLGA), to improve the efficiency of ofloxacin delivery at the site of action and inhibition of its extrusion.…”

“…PEGylation increased bacterial membrane permeability, allowing the accumulation of mPEG–PLGA nanoparticles inside the cells to a greater extent than PLGA nanoparticles. The nanoformulation also delayed the development of bacterial resistance in comparison with the free drug [30]. …”

A brief perspective on the diverging theories of lymphatic targeting with colloids

“…Furthermore, in addition to providing the hydrophilic surface required for lymphatic uptake, PEGylation also reduces the electrostatic interaction between the surface of the colloid and the components of the interstitial matrix by providing a neutral charge, which assists its drainage into the lymphatics. Thus, PEGylation has a positive impact not only in providing stealth attributes to colloids in blood [23][24][25][26] but also in facilitating their drainage from the site of injection to the lymphatics.…”

“…Interestingly, inhibiting phagocytosis using dextran as an adjuvant increased both lymphatic uptake and residence time of PEGylated colloids. 21 PEGylation can be applied in developing various nanoparticulate carriers like dendrimers, 10 PRINT (particle replication in nonwetting templates) hydrogels, 28 magnetic carbon nanotubes with PEG groups, 29 solid lipid nanoparticles, 3 polymeric nanoparticles, 24 liposomes, 25 and so on. Furthermore, a glance at a few of the promising nanopharmaceuticals in clinical use or undergoing trials like Oncaspar (PEGylated l-asperginase for acute lymphoblastic leukemia), Genexol (PEGylated block polymer containing an anticancer drug for metastatic breast cancer), and Lipo-dox and ThermoDox (PEGylated liposomal forms of doxorubicin) highlights the utility of PEGylation.…”