Abstract
Biocompatible polymeric materials with potential to form functional structures in association with different therapeutic molecules have a high potential for biological, medical and pharmaceutical applications. Therefore, the capability of the inclusion of nano-Complex formed between the sodium salt of poly(maleic acid-alt-octadecene) and a β-lactam drug (ampicillin trihydrate) to avoid the chemical and enzymatic degradation and enhance the biological activity were evaluated. PAM-18Na was produced and characterized, as reported previously. The formation of polymeric hydrophobic aggregates in aqueous solution was determined, using pyrene as a fluorescent probe. Furthermore, the formation of polymer-drug nano-complexes was characterized by Differential Scanning Calorimetry-DSC, viscometric, ultrafiltration/centrifugation assays, zeta potential and size measurements were determined by dynamic light scattering-DLS. The PAM-18Na capacity to avoid the chemical degradation was studied through stress stability tests. The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains. When ampicillin was associated with PAM-18Na, the half-life time in acidic conditions increased, whereas both the enzymatic degradation and the minimum inhibitory concentration decreased to a 90 and 75%, respectively. These results suggest a promissory capability of this polymer to protect the β-lactam drugs against chemical, enzymatic and biological degradation.
Highlights
Nowadays, bacterial antibiotic resistance stands as a significant public health problem in our society and, the considerable challenge of finding new antibiotic molecules or improving the activity of the existing ones demands a joint effort of multiple disciplines [1,2,3]
The capability of the inclusion of nano-Complex formed between the sodium salt of poly(maleic acid-alt-octadecene) and a β-lactam drug to avoid the chemical and enzymatic degradation and enhance the biological activity were evaluated
The enzymatic degradation was evaluated from a pure β-lactamase, while the biological degradation was determined by different β-lactamase producing Staphylococcus aureus strains
Summary
Bacterial antibiotic resistance stands as a significant public health problem in our society and, the considerable challenge of finding new antibiotic molecules or improving the activity of the existing ones demands a joint effort of multiple disciplines [1,2,3]. MRSA infections are commonly treated with non-β-lactam antibiotics like clindamycin but there are resistant strains as well These strategies involve the use of new molecules that merely test the refined ability of the microbes to evolve and adapt. In more concentrated solutions, PAM-18Na forms multimolecular aggregates This polymer has been able to solubilize different organic molecules such as alkyl-phenols [25] and N-alkyl-nitroimidazoles [22]. Based on these observations we hypothesized that PAM-18Na polymer could be useful to protect β-lactam antibiotics from the action of β-lactamases and improves their effect on antibiotic-resistant bacteria. Our results suggest a promissory capability the polymer PAM-18Na to protect the β-lactam drugs against chemical and biological degradation through the formation of a polymer-drug inclusion nano-complex in aqueous media
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