Therapeutic efficacy of liposome-entrapped rifampin against Mycobacterium avium complex infection induced in mice

Saito, Hajime; Tomioka, Haruaki

doi:10.1128/aac.33.4.429

Cited by 48 publications

(20 citation statements)

References 17 publications

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“…The present study demonstrates that liposome encapsulation of the drug further enhances intracellular drug incorporation. Similar increases in drug uptake by macrophages after liposomal drug encapsulation have been reported for kanamycin (30) and rifampin (29).…”

supporting

confidence: 79%

“…Increased therapeutic efficacy has been demonstrated following liposome encapsulation of streptomycin (31), amikacin (11), rifampin (29), and kanamycin (30). It was therefore thought that it would be of interest to know whether the therapeutic efficacies of clarithromycin and ofloxacin could be improved by liposome encapsulation.…”

mentioning

confidence: 99%

“…Delivery of drugs to phagocytic cells by liposomes resulted in greater efficacy against a number of intracellular pathogens including Listeria monocytogenes (2). Also, several laboratories have reported increased efficacies of liposome-entrapped antimycobacterial agents against MAI infections (11,29,30,31). Free clarithromycin demonstrated activity much greater than that of free ofloxacin, and this is in agreement with results of previous studies that used an in vitro cell model similar to the one used in the present study (7,25,27).…”

mentioning

confidence: 99%

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Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages

Onyeji

Nightingale

Nicolau

et al. 1994

Antimicrob Agents Chemother

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The therapeutic efficacies of liposome-encapsulated ofloxacin and clarithromycin against Mycobacterium avium-M. intraceilulare (MAI) were evaluated in a model of intramacrophage infection. Liposome encapsulation was found to markedly enhance the uptake of each of the drugs by human macrophages. The human blood-derived macrophages were infected at day 7 of culture with MAI. Treatment was initiated 24 h after the infection, and the number of intracellular bacteria was determined at days 2, 3, and 4. Liposome entrapment of either ofloxacin or clarithromycin significantly (P < 0.005) enhanced the activities of the drugs when compared with the antimycobacterial effects of equivalent concentrations of the free (unentrapped) drugs. The drugs were used at concentrations close to their clinically achievable peak levels. The efficacy of clarithromycin, either in the free or liposome-entrapped form, was markedly higher than that of ofloxacin. Liposomeencapsulated ofloxacin or clarithromycin plus ethambutol was, in each case, more effective in organism eradication (P < 0.005) than each agent used singly. These results suggest that liposome-encapsulated clarithromycin may be more effective than the free form of the drug against MAI infections in vivo, and the use of a combination therapy with ethambutol could further enhance the efficacy.

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confidence: 79%

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confidence: 99%

mentioning

confidence: 99%

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Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages

Onyeji

Nightingale

Nicolau

et al. 1994

Antimicrob Agents Chemother

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“…Isoniazid and pyrazinamide are inactive in vitro against a majority of MAC isolates (244), and neither of these drugs has a role in the treatment of MAC with the greatest burden of infection, saturating the mononuclear phagocyte system, thereby enhancing therapeutic efficacy and reducing drug toxicity. Although it is not known how liposomes deliver antimycobacterial agents to intracellular pathogens, liposomal encapsulation does enhance the activity of amikacin and rifampin in the beige mouse model (118,139,412). Colony counts were substantially reduced in the liver, spleen, and kidneys but only modestly reduced in the lungs compared with "free" drug.…”

Section: Therapeutic Agents and Treatmentmentioning

confidence: 99%

The Mycobacterium avium complex

1993

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Mycobacterium avium complex (MAC) disease emerged early in the epidemic of AIDS as one of the common opportunistic infections afflicting human immunodeficiency virus-infected patients. However, only over the past few years has a consensus developed about its significance to the morbidity and mortality of AIDS. M. avium was well known to mycobacteriologists decades before AIDS, and the MAC was known to cause disease, albeit uncommon, in humans and animals. The early interest in the MAC provided a basis for an explosion of studies over the past 10 years largely in response to the role of the MAC in AIDS opportunistic infection. Molecular techniques have been applied to the epidemiology of MAC disease as well as to a better understanding of the genetics of antimicrobial resistance. The interaction of the MAC with the immune system is complex, and putative MAC virulence factors appear to have a direct effect on the components of cellular immunity, including the regulation of cytokine expression and function. There now is compelling evidence that disseminated MAC disease in humans contributes to both a decrease in the quality of life and survival. Disseminated disease most commonly develops late in the course of AIDS as the CD4 cells are depleted below a critical threshold, but new therapies for prophylaxis and treatment offer considerable promise. These new therapeutic modalities are likely to be useful in the treatment of other forms of MAC disease in patients without AIDS. The laboratory diagnosis of MAC disease has focused on the detection of mycobacteria in the blood and tissues, and although the existing methods are largely adequate, there is need for improvement. Indeed, the successful treatment of MAC disease clearly will require an early and rapid detection of the MAC in clinical specimens long before the establishment of the characteristic overwhelming infection of bone marrow, liver, spleen, and other tissue. Also, a standard method of susceptibility testing is of increasing interest and importance as new effective antimicrobial agents are identified and evaluated. Antimicrobial resistance has already emerged as an important problem, and methods for circumventing resistance that use combination therapies are now being studied.

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“…At different time intervals, mice were sacrificed, and their organs, such as lungs, liver and spleen, were removed. Ten-percent tissue homogenates of the organs were prepared in 0.05 M PBS (pH 7.2), and levels of INH and RIF in the organs were determined by spectrofluorimetric assay (14) and by microbiological assay, respectively (13). Results were expressed as the concentrations of drugs obtained in micrograms per milliliter of tissue homogenates.…”

mentioning

confidence: 99%

Therapeutic Efficacy of Poly( dl -Lactide-Co-Glycolide)-Encapsulated Antitubercular Drugs against Mycobacterium tuberculosis Infection Induced in Mice

Dutt

Khuller

2001

Antimicrob Agents Chemother

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Poly(DL-lactide-co-glycolide) (PLG) microparticles were developed as carriers for isoniazid and rifampin in order to improve compliance of tuberculous chemotherapy. Antitubercular drugs encapsulated in PLG polymers and injected in a single dose subcutaneously resulted in a sustained release (up to 6 weeks) of drugs in various organs of mice. Further, Mycobacterium tuberculosis H 37 Rv-infected animals given a single shot of chemotherapy in PLG microparticles exhibited a better or equivalent clearance of CFU in various organs compared to those given a daily administration of free drugs.In the last decade, tuberculosis (TB) has reemerged as one of the leading causes of death (15). Short-course chemotherapy forms the backbone of antitubercular chemotherapy. Firstline drugs for therapy for TB are generally effective when used properly. However, it has been suggested that one of the major reasons for the increased numbers of multidrug-resistant strains of Mycobacterium tuberculosis is inefficient therapy, probably due to lack of compliance by patients (7). Tuberculocidal therapies that reduce the dosing schedule of the drugs should greatly increase patient compliance. In this regard, microencapsulation technology using various types of polymers could be used to deliver the required doses of the drugs for prolonged time periods by a single shot without causing any toxicity. For this purpose, various types of polymers, notably those of lactic and glycolic acids and their copolymers, such as poly(DL-lactide-co-glycolide) (PLG), have been employed as antitubercular drug delivery vehicles (6,8). PLG polymers, which are completely biodegradable and biocompatible (1), can be easily formulated into various types of delivery vehicles (5) and administered by various routes (3, 4). In the present communication, we report on the use of PLG microparticles (PLG-mps) as carriers for two of the major front-line antitubercular drugs, i.e., isoniazid (INH) and rifampin (RIF), and their chemotherapeutic potential against experimental tuberculosis in a murine model. PLG-mps containing entrapped antitubercular drugs (INH and RIF) were prepared by the double-emulsification solvent evaporation procedure as described by Edwards et al. (3) with slight modifications. Different groups of 6-to 8-week-old laca mice (weight, 18 to 20 g) of either sex were injected subcutaneously with drugs (INH and RIF) encapsulated in PLG-mps and with free drugs (INH and RIF). The doses of INH and RIF were 75 and 85 mg/kg of body weight of mice, respectively. Controls consisted of mice administered empty PLG-mps and phosphate-buffered saline (PBS) or normal saline. At different time intervals, mice were sacrificed, and their organs, such as lungs, liver and spleen, were removed. Ten-percent tissue homogenates of the organs were prepared in 0.05 M PBS (pH 7.2), and levels of INH and RIF in the organs were determined by spectrofluorimetric assay (14) and by microbiological assay, respectively (13). Results were expressed as the concentrations of drugs obtained in ...

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Therapeutic efficacy of liposome-entrapped rifampin against Mycobacterium avium complex infection induced in mice

Cited by 48 publications

References 17 publications

Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages

Efficacies of liposome-encapsulated clarithromycin and ofloxacin against Mycobacterium avium-M. intracellulare complex in human macrophages

The Mycobacterium avium complex

Therapeutic Efficacy of Poly( dl -Lactide-Co-Glycolide)-Encapsulated Antitubercular Drugs against Mycobacterium tuberculosis Infection Induced in Mice

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