Voltammetric study of the partitioning of macrolide antibiotics at the water/nitrobenzene interface. Relationship to the pharmacokinetic profiling of macrolides

Mandić, Zoran

doi:10.5599/admet.2.3.46

Cited by 10 publications

(10 citation statements)

References 21 publications

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“…These results are a consequence of the physicochemical properties of AZI and the liposomal constituents, both affecting encapsulation of the drug. AZI, even in the form of dihydrate, exhibits lipophilic features (log P =3.98),13 therefore it is expected to become accommodated within the liposome bilayers. However, molecular weight of AZI is rather large (Mw 785),13 restricting its incorporation within bilayers.…”

Section: Resultsmentioning

confidence: 99%

“…It is recommended for the treatment of respiratory, skin and soft tissue infections, including sexually transmitted bacterial diseases caused by C. trachomatis and Neisseria gonorrhoeae 11,12. AZI is usually available as a dihydrate (Mw 785) and is characterized by its limited solubility in water (log P =3.98) 13. Incorporation of AZI into liposomes could increase its solubility, favor its cervicovaginal biocompatibility, and enable prolonged AZI release, permitting higher local drug concentrations.…”

Section: Introductionmentioning

confidence: 99%

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<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Vanić¹,

Rukavina²,

Manner³

et al. 2019

IJN

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Background Efficient localized cervicovaginal antibacterial therapy, enabling the delivery of antibiotic to the site of action at lower doses while escaping systemic drug effects and reducing the risk of developing microbial resistance, is attracting considerable attention. Liposomes have been shown to allow sustained drug release into vaginal mucosa and improve delivery of antibiotics to bacterial cells and biofilms. Azithromycin (AZI), a potent broad-spectrum macrolide antibiotic, has not yet been investigated for localized therapy of cervicovaginal infections, although it is administered orally for the treatment of sexually transmitted diseases. Encapsulation of AZI in liposomes could improve its solubility, antibacterial activity, and allow the prolonged drug release in the cervicovaginal tissue, while avoiding systemic side effects. Purpose The objective of this study was to develop AZI-liposomes and explore their potentials for treating cervicovaginal infections. Methods AZI-liposomes that differed in bilayer elasticity/rigidity and surface charge were prepared and evaluated under simulated cervicovaginal conditions to yield optimized liposomes, which were assessed for antibacterial activity against several planktonic and biofilm-forming Escherichia coli strains and intracellular Chlamydia trachomatis, ex vivo AZI vaginal deposition/penetration, and in vitro cytotoxicity toward cervical cells. Results Negatively charged liposomes with rigid bilayers (CL-3), propylene glycol liposomes (PGL-2) and deformable propylene glycol liposomes (DPGL-2) were efficient against planktonic E. coli ATCC 700928 and K-12. CL-3 was superior for preventing the formation of E. coli ATCC 700928 and K-12 biofilms, with IC 50 values (concentrations that inhibit biofilm viability by 50%) up to 8-fold lower than those of the control (free AZI). DPGL-2 was the most promising for eradication of already formed E. coli biofilms and for treating C. trachomatis infections. All AZI-liposomes were biocompatible with cervical cells and improved localization of the drug inside vaginal tissue compared with the control. Conclusion The performed studies confirm the potentials of AZI-liposomes for localized cervicovaginal therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Vanić¹,

Rukavina²,

Manner³

et al. 2019

IJN

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“…4). Since macrolides, such as roxithromycin and azithromycin, are highly lipophilic [46,47], they were thought to easily penetrate into the cytoplasm of mast cells through their plasma membranes [29]. This may allow the drugs to directly influence the intracellular signaling pathways responsible for mast cell growth or survival [15].…”

Section: Discussionmentioning

confidence: 99%

“…This may allow the drugs to directly influence the intracellular signaling pathways responsible for mast cell growth or survival [15]. On the other hand, since clarithromycin is less lipophilic than the other macrolides [46,47], this drug is not likely to be accumulated inside of the plasma membranes. However, in a previous in vitro study, clarithromycin, among macrolide antibiotics, most effectively exerted membrane-stabilizing effects on erythrocytes [48], indicating its direct interaction with the plasma membranes.…”

Section: Discussionmentioning

confidence: 99%

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Kazama¹,

Saito²,

Baba³

et al. 2016

Chemotherapy

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Background: Macrolides, such as clarithromycin, have antiallergic properties. Since exocytosis in mast cells is detected electrophysiologically via changes in membrane capacitance (Cm), the absence of such changes due to the drug indicates its mast cell-stabilizing effect. Methods: Employing the whole-cell patch clamp technique in rat peritoneal mast cells, we examined the effects of clarithromycin on Cm during exocytosis. Using a water-soluble fluorescent dye, we also examined its effect on deformation of the plasma membrane. Results: Clarithromycin (10 and 100 μM) significantly inhibited degranulation from mast cells and almost totally suppressed the GTP-γ-S-induced increase in Cm. It washed out the trapping of the dye on the surface of mast cells. Conclusions: This study provides for the first time electrophysiological evidence that clarithromycin dose-dependently inhibits the process of exocytosis. The mast cell-stabilizing action of clarithromycin may be attributable to its counteractive effect on plasma membrane deformation induced by exocytosis.

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“…The ability to easily and quickly refresh the electrode surface before each measurement allows the Hg(Ag)FE to be applied in adsorptive stripping measurements [39], as in the case of EES [35], doxorubicin [41], closantel [42] and chlornitrofen [54]. When considering the structure of EES and its affinity to the Hg (Ag)FE under optimized measurement conditions [35] and the three semi-synthetic macrolide antibiotic target analytes, it can be noted that -beside of different possible electroactive centers -all of them are amines, with pK a values between 8.1 and 9.5 (for more details see Table 1) [55][56][57][58][59][60][61][62][63][64][65][66][67][68].…”

Section: Loq Was 2á10mentioning

confidence: 99%

Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver – amalgam film electrode

Vajdle

Guzsvány

Škorić

et al. 2017

Electrochimica Acta

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The renewable silver-amalgam film electrode (Hg(Ag)FE) was applied for voltammetric characterization and determination of semi-synthetic macrolide antibiotics azithromycin (AZI), clarithromycin (CLA) and roxithromycin (ROX) in the Britton-Robinson buffer as supporting electrolyte ranging the pH from 4.0 to 11.9. All three macrolides showed reduction signals in fairly negative potential range.During direct cathodic square wave voltammetric (SWV) investigations conducted over the potential range from À0.75 V to À2.00 V vs SCE, either one or two reduction peaks were obtained in the potential range from À1.5 to À1.9 V. The shapes and intensities of the signals depend on the applied pH values in wider pH ranges. For analytical purposes concerning the development of direct cathodic SWV and adsorptive stripping SWV (SW-AdSV) methods the neutral and slightly alkaline media were suitable as pH 7.2, pH 7.4 and pH 7.0 for AZI, CLA and ROX, respectively. Based on the cyclic voltammograms recorded at these pH values, adsorption-controlled electrode kinetics process can be proposed for all three macrolides. Furthermore, the water suppressed 1 H NMR measurements in the pH range between 6.0 and 10.5 indicated that the macrolide molecules at the optimal analytical conditions are predominantly in protonated form via their tertiary amino groups which supported in all three cases their adsorption on the appropriately polarized Hg(Ag)FE electrode. The optimized direct cathodic SWV methods showed good linearity in concentration ranges 4.81-23.3 mg mL À1 , 1.96-28.6 mg mL À1 and 1.48-25.9 mg mL À1 for AZI, CLA and ROX, respectively. The development of the SW-AdSV methods resulted in the linear responses at lower concentration ranges as 1.0-2.46 mg mL À1, 0.05-0.99 mg mL À1 and 0.10-0.99 mg mL À1 , for AZI, CLA and ROX, respectively. The relative standard deviation for all developed methods was not higher than 1.0% except the SWV method for AZI with 4.7%. In the case of all three investigated macrolide antibiotics the protonated form of the tertiary amino group(s) at appropriate accumulation potential and time favored the adsorption of the ionic form of the target molecules offering the opportunity for the development of SW-AdSV methods for their trace level analysis on Hg(Ag)FE. Optimized SW-AdSV method was applied for determination of ROX in pharmaceutical preparation Runac

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Voltammetric study of the partitioning of macrolide antibiotics at the water/nitrobenzene interface. Relationship to the pharmacokinetic profiling of macrolides

Abstract: The ion transfer of a series of ionised 14-and 15-membered

Cited by 10 publications

References 21 publications

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

<p>Azithromycin-liposomes as a novel approach for localized therapy of cervicovaginal bacterial infections</p>

Clarithromycin Dose-Dependently Stabilizes Rat Peritoneal Mast Cells

Voltammetric behavior and determination of the macrolide antibiotics azithromycin, clarithromycin and roxithromycin at a renewable silver – amalgam film electrode

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