Abstract
Recent advances in the field of nanotechnology such as nanoencapsulation offer new biomedical applications, potentially increasing the scope and efficacy of therapeutic drug delivery. In addition, the discovery and development of novel biocompatible polymers increases the versatility of these encapsulating nanostructures, enabling chemical properties of the cargo and vehicle to be adapted to specific physiological requirements. Here, we evaluate the capacity of various polymeric nanostructures to encapsulate various antibiotics of different classes, with differing chemical structure. Polymers were sourced from two separate derivatives of poly(methyl vinyl ether-alt-maleic anhydride) (PMVE/MA): an acid (PMVE/MA-Ac) and a monoethyl ester (PMVE/MA-Es). Nanoencapsulation of antibiotics was attempted through electrospinning, and nanoparticle synthesis through solvent displacement, for both polymers. Solvent incompatibilities prevented the nanoencapsulation of amikacin, neomycin and ciprofloxacin in PMVE/MA-Es nanofibers. However, all compounds were successfully loaded into PMVE/MA-Es nanoparticles. Encapsulation efficiencies in nanofibers reached approximately 100% in all compatible systems; however, efficiencies varied substantially in nanoparticles systems, depending on the tested compound (14%–69%). Finally, it was confirmed that both these encapsulation processes did not alter the antimicrobial activity of any tested antibiotic against Staphylococcus aureus and Escherichia coli, supporting the viability of these approaches for nanoscale delivery of antibiotics.
Highlights
Antibiotics are the most reliable weapon against infectious diseases of bacterial origin
All the antibiotics tested were soluble in water, and encapsulate into poly(methyl vinyl ether-alt-maleic anhydride) (PMVE/MA)-Ac nanofibers, but only cefotaxime was soluble in ethanol, and the only one loadable into PMVE/MA-Es nanofibers
As many drugs are hydrophobic, the description of electrospinnable polymers with properties compatible for encapsulating hydrophobic compounds, is of great importance in order to incorporate such molecules into electrospun nanofibers while maintaining their biological functionality. This issue has been revisited by several authors recently [21,22]. These polymers might work as a shell phase in both co-axial and layer-by-layer electrospinning in order to either manipulate the delivery dynamics of high hydrophilic molecules to the particular requirements or to adapt the delivery system to the needs of the biological context [23,24]
Summary
Antibiotics are the most reliable weapon against infectious diseases of bacterial origin. The dramatic diminishment in the rate of discovery of new antibiotics limits our response to pathogens resistant to conventional antibiotics and to new emerging diseases. The scientific community is developing alternative strategies to increase the effectiveness, and/or to overcome the limitations, of existing antibiotics [1,2]. In this context, recent advances in the field of nanotechnology offer new tools such as nanoencapsulation: the loading of pharmaceutical agents within nanomaterials [3,4]. With the corresponding modifications, these nanostructured systems can facilitate targeted drug delivery and/or specific controlled-release kinetics, thereby increasing the effectiveness of the treatment and, reducing necessary dosage and side effects [3,4]
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