Encapsulation of Amikacin into Microparticles Based on Low-Molecular-Weight Poly(lactic acid) and Poly(lactic acid-co-polyethylene glycol).

Marta Glinka,Justyna Kucińska-Lipka,Andrzej Wasik,Eva Domincova Bergerova,Katerina Filatova,Vladimir Sedlařík

doi:10.1021/acs.molpharmaceut.1c00193

Marta Glinka, Justyna Kucińska-Lipka + Show 4 more

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https://doi.org/10.1021/acs.molpharmaceut.1c00193

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Abstract

The aim of this study was to fabricate novel microparticles (MPs) for efficient and long-term delivery of amikacin (AMI). The emulsification method proposed for encapsulating AMI employed low-molecular-weight poly(lactic acid) (PLA) and poly(lactic acid-co-polyethylene glycol) (PLA–PEG), both supplemented with poly(vinyl alcohol) (PVA). The diameters of the particles obtained were determined as less than 30 μm. Based on an in-vitro release study, it was proven that the MPs (both PLA/PVA- and PLA–PEG/PVA-based) demonstrated long-term AMI release (2 months), the kinetics of which adhered to the Korsmeyer–Peppas model. The loading efficiencies of AMI in the study were determined at the followings levels: 36.5 ± 1.5 μg/mg for the PLA-based MPs and 106 ± 32 μg/mg for the PLA–PEG-based MPs. These values were relatively high and draw parallels with studies published on the encapsulation of aminoglycosides. The MPs provided antimicrobial action against the Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae bacterial strains. The materials were also comprehensively characterized by the following methods: differential scanning calorimetry; gel permeation chromatography; scanning electron microscopy; Fourier transform infrared spectroscopy–attenuated total reflectance; energy-dispersive X-ray fluorescence; and Brunauer–Emmett–Teller surface area analysis. The findings of this study contribute toward discerning new means for conducting targeted therapy with polar, broad spectrum antibiotics.

Highlights

Amikacin (AMI) is a semisynthetic, broad spectrum aminoglycoside antibiotic, primarily used against infections caused by Gram-negative bacteria
Determining the primary properties of the prepared poly(lactic acid) (PLA) and poly(lactic acid-co-polyethylene glycol) (PLA−PEG) after synthesis was performed by differential scanning calorimetry (DSC; the results are given in Table 1) and gel permeation chromatography (GPC)
The PLA−PEG copolymer exhibited reduction in thermal stability compared to PLA, in addition to which crystallization for the former occurred at a temperature of less than 10 °C, unlike the latter, and its content of the crystalline phase was higher by approximately 15 J/g

Summary

Introduction

Amikacin (AMI) is a semisynthetic, broad spectrum aminoglycoside antibiotic, primarily used against infections caused by Gram-negative bacteria. AMI is known to have toxic side effects, especially nephrotoxicity and ototoxicity due to its low therapeutic index. Another drawback relates to poor absorption if administered orally, as a consequence of the polycationic nature of the molecule. For these reasons, medicating with AMI has to be a strictly controlled process.[2,3]

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