Abstract
This study was focused on synthesizing, characterizing and evaluating the biological potential of Polyelectrolyte Complex Nanoparticles (PECNs) loaded with the antibiotic ampicillin. For this, the PECNs were produced initially by polyelectrolytic complexation (bottom-up method) and subsequently subjected to ultra-high pressure homogenization-UHPH (top-down method). The synthetic polymeric materials corresponding to the sodium salt of poly(maleic acid-alt-octadecene) (PAM-18Na) and the chloride salt of Eudragit E-100 (EuCl) were used, where the order of polyelectrolyte complexation, the polyelectrolyte ratio and the UHPH conditions on the PECNs features were evaluated. Likewise, PECNs were physicochemically characterized through particle size, polydispersity index, zeta potential, pH and encapsulation efficiency, whereas the antimicrobial effect was evaluated by means of the broth microdilution method employing ampicillin sensitive and resistant S. aureus strains. The results showed that the classical method of polyelectrolyte complexation (bottom-up) led to obtain polymeric complexes with large particle size and high polydispersity, where the 1:1 ratio between the titrant and receptor polyelectrolyte was the most critical condition. In contrast, the UHPH technique (top-down method) proved high performance to produce uniform polymeric complexes on the nanometric scale (particle size < 200 nm and PDI < 0.3). Finally, it was found there was a moderate increase in antimicrobial activity when ampicillin was loaded into the PECNs.
Highlights
In the last decade, there has been a remarkable increase in research related to nanoparticles (NPs) applied to the medical field, ranging from inorganic to organic systems [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]
The polydispersity index (PDI) of the polyelectrolytic complexes (PECs) and their respective controls are shown in Figure 3A–F and the results revealed that the PDI exhibited a similar behavior to those observed in particle size
According to the results obtained by z-potential (Figure 4), the anionic PAM18Na is located on the surface of the Polyelectrolyte Complex Nanoparticles (PECNs) for the EuCl-PAM18Na (1:3 ratio) family, and this polymer is constituted by carboxylate groups, which would have the ability to change the internal pH of the bacterial cell, leading to the interruption of the transport of the drug, either by changes in the permeability of the cell membrane or by the alteration of the proton flow mechanisms between the inside and the outside of the cell
Summary
There has been a remarkable increase in research related to nanoparticles (NPs) applied to the medical field, ranging from inorganic to organic systems [1,2,3,4,5,6,7,8,9,10,11,12,13,14,15]. Regarding PECNs, these can be obtained by several methodologies, being the traditional process of polyelectrolytic complexation (bottom-up method) one of the most used [63,64,65,66,67] This technique is based on the spontaneous interpolymeric aggregation given by the electrostatic attraction, when a cationic and anionic polyelectrolyte are mixed in aqueous solution. This polyelectrolytic complexation seems in principle to be an easy methodology to perform; it is the opposite, since it depends on multiple intrinsic and extrinsic variables [66]. Some of these intrinsic variables are the chemical nature, molecular weight, and fraction charge of the polymer
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