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. 2021 Mar 24;13(4):435.
doi: 10.3390/pharmaceutics13040435.

Mixed Pluronic-Cremophor Polymeric Micelles as Nanocarriers for Poorly Soluble Antibiotics-The Influence on the Antibacterial Activity

Maria Antonia Tănase  1 , Adina Raducan  1 , Petruţa Oancea  1 , Lia Mara Diţu  2 , Miruna Stan  3 , Cristian Petcu  4 , Cristina Scomoroşcenco  4 , Claudia Mihaela Ninciuleanu  4 , Cristina Lavinia Nistor  4 , Ludmila Otilia Cinteza  1
Affiliations

Mixed Pluronic-Cremophor Polymeric Micelles as Nanocarriers for Poorly Soluble Antibiotics-The Influence on the Antibacterial Activity

Maria Antonia Tănase et al. Pharmaceutics. .

Abstract

In this work, novel polymeric mixed micelles from Pluronic F127 and Cremophor EL were investigated as drug delivery systems for Norfloxacin as model antibiotic drug. The optimal molar ratio of surfactants was determined, in order to decrease critical micellar concentration (CMC) and prepare carriers with minimal surfactant concentrations. The particle size, zeta potential, and encapsulation efficiency were determined for both pure and mixed micelles with selected composition. In vitro release kinetics of Norfloxacin from micelles show that the composition of surfactant mixture generates tunable extended release. The mixed micelles exhibit good biocompatibility against normal fibroblasts MRC-5 cells, while some cytotoxicity was found in all micellar systems at high concentrations. The influence of the surfactant components in the carrier on the antibacterial properties of Norfloxacin was investigated. The drug loaded mixed micellar formulation exhibit good activity against clinical isolated strains, compared with the CLSI recommended standard strains (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29213, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922). P. aeruginosa 5399 clinical strain shows low sensitivity to Norfloxacin in all tested micelle systems. The results suggest that Cremophor EL-Pluronic F127 mixed micelles can be considered as novel controlled release delivery systems for hydrophobic antimicrobial drugs.

Keywords: Pluronic F127; antibiotics; drug delivery; mixed polymeric micelles.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Schematic representation of the obtaining procedure for the Norfloacin loaded Pluronic F127—Cremophor EL mixed micelles.
Figure 2
Figure 2
Size and size distribution of the micelles: (a) Cremophor EL, (b) Pluronic F127, (c) Mixed Cremophor EL-Pluronic F127 micellar system, (d) Norfloxacin loaded mixed Cremophor EL-Pluronic F127 micellar system.
Figure 3
Figure 3
FTIR spectra of (1) Norfloxacin, (2) Cremophor EL, (3) Pluronic F127, (4) Norfloxacin in Cremophor EL micelles 100 µg/mL, (5) Norfloxacin in mixed micelles Cremophor EL-Pluronic F127 and (6) Norfloxacin in Pluronic F127 micelles 100 µg/mL.
Figure 4
Figure 4
In vitro drug release profile for NFLX in Cremohor EL, Pluronic F127 and CrEL-Pl F127 (α = 0.2) mixed micelles.
Figure 5
Figure 5
In vitro drug release profile for NFLX in mixed CrEL-Pl F127 (α = 0.2) micelles at various temperature (a) and pH values (b).
Figure 6
Figure 6
Cell viability results obtained by MTT assay after 24 and 48 h of cell growth in the presence of surfactants. Results are presented as mean ± standard deviation of three independent experiments (* p < 0.05, ** p < 0.01 and *** p < 0.001 compared with control).
Figure 6
Figure 6
Cell viability results obtained by MTT assay after 24 and 48 h of cell growth in the presence of surfactants. Results are presented as mean ± standard deviation of three independent experiments (* p < 0.05, ** p < 0.01 and *** p < 0.001 compared with control).
Figure 7
Figure 7
NO release measured by Griess assay after 24 and 48 h of cell growth in the presence of surfactants. Results are presented as mean ± standard deviation of three independent experiments (** p < 0.01 and *** p < 0.001 compared with control).
Figure 7
Figure 7
NO release measured by Griess assay after 24 and 48 h of cell growth in the presence of surfactants. Results are presented as mean ± standard deviation of three independent experiments (** p < 0.01 and *** p < 0.001 compared with control).
Figure 8
Figure 8
Aspect of the inhibition zones for microorganisms (a) Staphylococcus aureus ATCC 25923, (b) Pseudomonas aeruginosa ATCC 27853 and (c) Escherichia coli ATCC 25922. The samples are denoted P1 = NFLX in water; P2 = NFLX in DMSO; P3 = NFLX in Cremophor EL micellar solution; P4 = NFLX in Pluronic F127 micellar solution; P5 = NFLX in mixed micellar solution, while M1, M2 and M3 are empty micelles of Cremophor EL, Pluronic F127 and mixed micelles, respectively.
Figure 9
Figure 9
Graphic representation of inhibition zone diameters (mm).
Figure 10
Figure 10
Graphic representation of minimal inhibitory concentration values for: (a) Gram negative tested strains and (b) Gram positive tested strains.
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