The Formation of β-Cyclodextrin Complexes with Levofloxacin and Ceftriaxone as an Approach to the Regulation of Drugs’ Pharmacokinetic

Abstract

— The study has been devoted to the complexation of hydroxypropyl-β-cyclodextrin (HPCD) with antibacterial drugs, namely, ceftriaxone (CT) and levofloxacin (LV), which are used to treat respiratory diseases, including bacterial infections of the respiratory tract. FTIR and NMR spectroscopic investigations have shown that the LV–HPCD complex is formed mainly due to the inclusion of the aromatic fragment of LV into the HPCD cavity; while the CT–HPCD complex is realized on the HPCD surface. Being a more hydrophobic molecule, LV forms ten times stronger complexes with HPCD than does CT: K disLV-HPCD ~ 10 –3 M, while K disCT-HPCD ~10 –2 M at pH 7.4. It has been shown that, for singly charged forms of the drugs, the complexes are two times more stable. Fluorescence spectroscopy has been employed to study the thermodynamic parameters for the interaction of dosage forms with human serum albumin. Negative values of Δ H and Δ S of the reaction have indicated both hydrogen bonding and van der Waals interactions during the complexation of both drugs with human serum albumin. It has been found that the protein is ~4 times more strongly bound to LV at 37°C as compared with CT. The data obtained will make it possible to improve the characteristics of the studied drugs and bring the methods of treating severe forms of respiratory diseases to a new level.

Cyclodextrins and Their Polymers Affect Human Serum Albumin’s Interaction with Drugs Used in the Treatment of Pulmonary Infections

“…The guest–host complexes of CD derivatives with Cef, Mer and Lev are well-studied in the literature [ 28 , 29 , 30 , 31 ]. For AM–CD complexes, the average binding constant (Ka) values are near 10 2 –10 3 M –1 , whereas for drug–CD polymers they might reach 10 5 M –1 [ 15 ].…”

“…Ksv allows the evaluation of fluorophore quenching by small molecules, taking into account both statistical and dynamic quenching. For small molar excesses, only statistical quenching is observed [ 29 ].…”

Human Serum Albumin Grafted by Monomeric and Polymeric β-Cyclodextrin as Drug Delivery System for Levofloxacin with Improved Pharmacological Properties

“…For the second system, non-covalent LV complexes were obtained with the conjugates HSA−HPCD conj and HSA−HPolS conj described above (Figure 2B). Cyclodextrins are able to form inclusion complexes with large binding constants of ~10 4 -10 6 M −1 [31,32] and non-covalent complexes with antibacterial molecules. One may expect that the formation of non-covalent complexes between LV and (HSA−HPCD) conj or (HSA−HPolS) conj (Figure 2B) would exhibit high binding affinities.…”

“…The detailed description of the interaction between LV and HSA has been previously elucidated [18,44,45]. In our previous works, we studied ternary systems where the drug is the included in the complex with monomeric or polymeric CDs [16,32,46,47]. Here, we studied the interactions of levofloxacin (LV) with HSA grafted with cyclodextrins (CDs) or CD polymers (CDPols).…”

Encapsulation of Ciprofloxacin into a Cyclodextrin Polymer Matrix: The Complex Formation with Human Serum Albumin and In Vitro Studies

“…where c is CF's concentration (µg/mL), S inh is the inhibition zone area (mm 2 ) [32,33]. Each sample was tested 3 times, and the data are presented with standard deviations.…”