Poly(ethylene glycol)–poly(vinylphosphonic acid) block copolymers (PEG-b-PVPA) of low average molar mass were synthesized by RAFT/MADIX polymerization. Their intrinsic properties (i.e. anionic-neutral character which brings both ability to strongly interact with cations and steric stabilization) allow the one-step in situ synthesis of water-dispersible iron oxide nanoparticles with controlled size and high colloidal stability. The effect of structural properties of the polymer (chain length of PEG and PVPA blocks) on the formation and/or stabilization of nanoparticles has been evaluated. Additionally, PVPA and PAA block complexing abilities were compared and the advantage of phosphonic acid groups over carboxylic acid groups was proven. Hemocompatibility tests carried out with the DHBCs alone and DHBC/iron oxide hybrid nanoparticles revealed that the hemolysis rates observed with phosphonated copolymers were much lower than for their carboxylated analogs.
1 May 2014 in International Journal of Nanomedicine
Superparamagnetic iron oxide nanoparticles (SPIONs) and their derivatives (aminosilane and gold-coated) have been widely investigated in numerous medical applications, including their potential to act as antibacterial drug carriers that may penetrate into bacteria cells and biofilm mass. Pseudomonas aeruginosa is a frequent cause of infection in hospitalized patients, and significant numbers of currently isolated clinical strains are resistant to standard antibiotic therapy. Here we describe the impact of three types of SPIONs on the growth of P. aeruginosa during long-term bacterial culture. Their size, structure, and physicochemical properties were determined using transmission electron microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy. We observed significant inhibition of P. aeruginosa growth in bacterial cultures continued over 96 hours in the presence of gold-functionalized nanoparticles (Fe3O4@Au). At the 48-hour time point, growth of P. aeruginosa, as assessed by the number of colonies grown from treated samples, showed the highest inhibition (decreased by 40%). These data provide strong evidence that Fe3O4@Au can dramatically reduce growth of P. aeruginosa and provide a platform for further study of the antibacterial activity of this nanomaterial.
Human plasma gelsolin (pGSN) is a multifunctional actin-binding protein involved in a variety of biological processes, including neutralization of pro-inflammatory molecules such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA) and modulation of host inflammatory response. It was found that PBP10, a synthetic rhodamine B-conjugated peptide, based on the phosphoinositide-binding site of pGSN, exerts bactericidal activity against Gram-positive and Gram-negative bacteria, interacts specifically with LPS and LTA, and limits microbial-induced inflammatory effects. The therapeutic efficiency of PBP10 when immobilized on the surface of iron oxide-based magnetic nanoparticles was not evaluated, to date. Using the human keratinocyte cell line HaCaT stimulated by bacterially-derived LPS and LTA as an in vitro model of bacterial infection, we examined the anti-inflammatory effects of nanosystems consisting of iron oxide-based magnetic nanoparticles with aminosilane (MNP@NH2) or gold shells (MNP@Au) functionalized by a set of peptides, derived from the phosphatidylinositol 4,5-bisphosphate (PIP2)-binding site of the human plasma protein gelsolin, which also binds LPS and LTA. Our results indicate that these nanosystems can kill both Gram-positive and Gram-negative bacteria and limit the production of inflammatory mediators, including nitric oxide (NO), reactive oxygen species (ROS), and interleukin-8 (IL-8) in the response to heat-killed microbes or extracted bacterial cell wall components. The nanoparticles possess the potential to improve therapeutic efficacy and are characterized by lower toxicity and improved hemocompatibility when compared to free peptides. Atomic force microscopy (AFM) showed that these PBP10-based nanosystems prevented changes in nanomechanical properties of cells that were otherwise stimulated by LPS. Neutralization of endotoxemia-mediated cellular effects by gelsolin-derived peptides and PBP10-containing nanosystems might be considered as potent therapeutic agents in the improved therapy of bacterial infections and microbial-induced inflammation.
The mucosal membrane of the oral cavity, due to its unique structure and availability, constitutes an appropriate site for the delivery of drugs, both with local and systemic effects. Mucoadhesive buccal films are drug dosage forms that due to their convenience of application, flexibility and size, are characterized by patients’ compliance. Sodium alginate and pectin are natural polymers from the polysaccharides group, with mucoadhesive properties, that are widely applied to obtain buccal films. However, their hydrophilic nature and poor water resistance limit their application in sustained drug release formulations. Hence, the aim of this investigation was to design alginate/pectin buccal films by a one-step crosslinking technique—with the application of calcium carbonate. This technique was applied to prepare crosslinked alginate and alginate/pectin mucoadhesive films with a model antifungal drug—posaconazole. The obtained formulations were evaluated for the impact of crosslinking and pectin’s presence on their pharmaceutical, mucoadhesive, mechanical and physicochemical properties. Additionally, the antifungal activity of the prepared films against Candida spp. was evaluated. It was shown that pectin’s presence in the formulations improved flexibility, mucoadhesion and antifungal activity. The crosslinking process reduced mucoadhesiveness and antifungal activity but significantly enhanced the mechanical properties and stability and enabled prolonged drug release.