UV spectroscopy and reverse-phase HPLC as novel methods to determine Capreomycin of liposomal fomulations

Róssi, Carlo; Fardella, Giuseppe; Chiappini, Ione; Perioli, Luana; Vescovi, Claudia; Ricci, Maurizio; Giovagnoli, Stefano; Scuota, Stefania

doi:10.1016/j.jpba.2004.06.015

Cited by 22 publications

(6 citation statements)

References 8 publications

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“…Plasma and BAL samples were analyzed for drug content by a modified HPLC assay (29). The limit of detection was 0.5 g/ml, the intraday variation was 8.64%, and the interday variation was 7.15%.…”

Section: Methodsmentioning

confidence: 99%

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

García-Contreras

Fiegel

Telko

et al. 2007

Antimicrob Agents Chemother

131

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Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content. Pharmacokinetic parameters were determined by noncompartmental methods with healthy guinea pigs after administration of capreomycin particles by insufflation. The efficacy of the particles was evaluated by histopathological analysis and in terms of wet organ weight and bacterial burden in TB-infected animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles showed significantly lower wet weights and smaller bacterial burdens than those of animals receiving any other treatment. These results were supported by histopathological analysis. The feasibility of inhaling capreomycin in a novel powder form, with the ultimate objective of the treatment of MDR-TB, is demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If applied to humans with MDR-TB, such a therapeutic approach might simplify drug delivery by eliminating injections and might reduce adverse effects through lowering the dose.Worldwide, there is an increase in multiple drug-resistant tuberculosis (MDR-TB), including reports of outbreaks of extensive MDR-TB in several countries (4, 36). Patients suffering from MDR-TB have infections which are resistant to at least two key drugs in the first-line regimen, namely, rifampin and isoniazid, in part as a consequence of poor compliance to the current first-line regimen (approximately 23% of active TB patients presently complete first-line treatment) (5). To treat MDR-TB, other, second-line antibiotics are needed and therapy lasts up to 2 years, typically requiring parenteral injection (2).Among the drugs injected is the polypeptide antibiotic capreomycin, the only second-line drug specifically indicated for MDR-TB. Capreomycin is a complex of four microbiologically active components that has been shown to be effective in combination with other appropriate anti-TB drugs in the treatment of pulmonary Mycobacterium tuberculosis infections when the primary agents (in particular isoniazid and rifampin) have become ineffective as a result of bacterial resistance or toxicity. The drug is painful to receive by injection and is associated with serious side effects, such as anorexia, thirst, anemia, and notably, nephrotoxicity and damage to the auditory and vestibular divisions of cranial nerv...

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Section: Methodsmentioning

confidence: 99%

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

García-Contreras

Fiegel

Telko

et al. 2007

Antimicrob Agents Chemother

131

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“…Rossi et al proposed these two methods as alternatives for the quantitation of Capreomycin in liposomal formulations. 32 They showed that both methods were valid alternatives for quantitative drug analysis, even though the UV-Vis spectrophotometric method presented less accurate than the HPLC in reversed-phase mode. In fact, the spectrophotometric analyses were inexpensive, easier and required a shorter time for experiments.…”

Section: Resultsmentioning

confidence: 99%

In Vitro Efficacy of Curcumin-Loaded Amine-Functionalized Mesoporous Silica Nanoparticles against MCF-7 Breast Cancer Cells

2022

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Purpose: Mesoporous silica nanoparticles (MSNs) have drawn substantial interest as drug nanocarriers for breast cancer therapy. Nevertheless, because of the hydrophilic surfaces, the loading of well-known hydrophobic polyphenol anticancer agent curcumin (Curc) into MSNs is usually very low. Methods: For this purpose, Curc molecules were loaded into amine-functionalized MSNs (MSNs-NH2-Curc) and characterized using TGA, FTIR, FE-SEM, TEM, and BET. MTT assay and confocal microscopy, respectively, were used to determine the cytotoxicity and cellular uptake of the MSNs-NH2-Curc in the MCF-7 breast cancer cells. Besides, the expression levels of apoptotic genes were evaluated via qPCR and western blot. Results: It was revealed that MSNs-NH2 possessed high values of drug loading efficiency and exhibited slow and sustained drug release compared to bare MSNs. According to the MTT findings, while the MSNs-NH2-Curc were nontoxic to the human non-tumorigenic MCF-10A cells at low concentrations, it could considerably decrease the viability of MCF-7 breast cancer cells compared to the free Curc in all concentrations after 24, 48 and 72 h exposure times. A cellular uptake study using confocal fluorescence microscopy confirmed the higher cytotoxicity of MSNs-NH2-Curc in MCF-7 cells. Further, it was found that the MSNs-NH2-Curc could drastically affect the mRNA and protein levels of Bax, Bcl-2, caspase 3, caspase 9, and hTERT relative to the free Curc treatment. Conclusion: Taken together, these preliminary results suggest the amine-functionalized MSNs-based drug delivery platform as a promising alternative approach for Curc loading and safe breast cancer treatment.

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“…Loaded liposomes can also be separated from a free unencapsulated drug using a dialysis membrane with the appropriate cut-off pore size [ 58 ]. Once drug-loaded liposomes are separated from a free drug, the lipid bilayer is disrupted, and the released drug is then quantified using various techniques such as spectrophotometry and high-performance liquid chromatography (HPLC) [ 59 ].…”

Section: Biophysical Characterization Of Liposomesmentioning

confidence: 99%

Liposomes in Cancer Therapy: How Did We Start and Where Are We Now

Fulton

Najahi‐Missaoui

2023

IJMS

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Since their first discovery in the 1960s by Alec Bangham, liposomes have been shown to be effective drug delivery systems for treating various cancers. Several liposome-based formulations received approval by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA), with many others in clinical trials. Liposomes have several advantages, including improved pharmacokinetic properties of the encapsulated drug, reduced systemic toxicity, extended circulation time, and targeted disposition in tumor sites due to the enhanced permeability and retention (EPR) mechanism. However, it is worth noting that despite their efficacy in treating various cancers, liposomes still have some potential toxicity and lack specific targeting and disposition. This explains, in part, why their translation into the clinic has progressed only incrementally, which poses the need for more research to focus on addressing such translational limitations. This review summarizes the main properties of liposomes, their current status in cancer therapy, and their limitations and challenges to achieving maximal therapeutic efficacy.

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UV spectroscopy and reverse-phase HPLC as novel methods to determine Capreomycin of liposomal fomulations

Cited by 22 publications

References 8 publications

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

Inhaled Large Porous Particles of Capreomycin for Treatment of Tuberculosis in a Guinea Pig Model

In Vitro Efficacy of Curcumin-Loaded Amine-Functionalized Mesoporous Silica Nanoparticles against MCF-7 Breast Cancer Cells

Liposomes in Cancer Therapy: How Did We Start and Where Are We Now

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