Self-assembled cyclodextrin-based nanoparticles for meropenem stabilization

Abstract Meropenem is a carbapenem antibiotic with ultrabroad spectrum of activity and active against bacterial strains resistant to other antibiotics. The drug is characterized by fast renal elimination and high instability in aqueous solution where it undergoes β-lactam ring opening with consequent loss of biological activity. The purpose of this study was to develop cyclodextrin (CD) based nanoparticles (NPs) for increased meropenem bioavailability and stability in aqueous solutions. Self-assembly nanoparticles are formed by carboxymethylcellulose (CMC) and quaternary amino βCD polymer (QAβCDp), NPs of CMC-QAβCDp with relatively narrow size distribution profile are spontaneously formed in aqueous solution. The NPs were characterized by UV-VIS spectroscopy, DLS size measurements, Zeta potential and NMR spectroscopy. The kinetic stability studies revealed that meropenem loaded NPs can slow down the β-lactam antibiotic hydrolysis at room temperature by nearly 30% while at 4 °C the hydrolysis is 63% slower. The NPs with mean hydrodynamic diameter of about 135 nm displayed size stability during three-month storage at 4 °C. Incorporation of meropenem into the NPs increased the drug permeation through semi-permeable membranes suggesting that the NPs could have positive effect on meropenem permeation through biological membranes.