P. JAEP and ERIC: alkalizing agents & Fluconazole synergy

[Guest guest]

and :

Looks like the dose of fulconazole can be reduced when the PH is

raised in the cell.

This is the same theory as Sam Donta's Lyme therapy -using HCQ to

alkalize the cell compartment so one of the tetracyclines can enter

the cell compartment and kill the intra cellular pathogen.

Anyone taken HCQ and fluconazole together?- what about Schardt's

IOWA group-?

Barb

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Pharm Res. 2004 Dec;21(12):2207-12. Related Articles, Links

Prophylactic role of liposomized chloroquine against murine

cryptococcosis less susceptible to fluconazole.

Khan MA, Jabeen R, Mohammad O.

Aligarh Muslim University, Aligarh 202002, India.

alammasood1@r...

PURPOSE: The prophylactic role of liposomized chloroquine (lip-CQ)

has been assessed against less susceptible Cryptococcus neoformans

infection in murine model. METHODS: In the current study, we

investigated the antifungal activity of lip-CQ against C. neoformans

in macrophages cell line (J 774) and murine model. Mice were

pretreated with free as well as liposomized formulations of CQ at

various doses. The anticryptococcal activity of fluconazole was

compared in mice with or without CQ pretreatment. The efficacy of CQ

prophylaxis was assessed by survival as well as colony forming units

(cfu) in brain and lungs of treated mice. RESULTS: Fluconazole alone

was not found significantly effective against C. neoformans in both

in vitro and in vivo studies. However, the antifungal activity of

fluconazole increases in chloroquine-pretreated mice. Lip-CQ was

found to be more effective in comparison to the same dose of free

chloroquine in reducing fungal burden from macrophages in vitro and

lungs and brain of C. neoformans infected mice.

CONCLUSIONS: The enhanced prophylactic activity of lip-CQ seems due

to rapid uptake of drug-containing liposomes by macrophages. The

liposome-mediated accumulation of CQ in macrophages makes the

environment unfavorable (alkaline) for the intracellular

multiplication of C. neoformans. Moreover, the increased incidence of

multi-drug resistance and diversity of pathogenic microorganisms

inhibited or killed by CQ makes it the drug of choice for

prophylactic therapy.

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J Antimicrob Chemother. 2005 Feb;55(2):223-8. Epub 2004 Dec 08.

Related Articles, Links

Enhanced anticryptococcal activity of chloroquine in

phosphatidylserine-containing liposomes in a murine model.

Khan MA, Jabeen R, Nasti TH, Mohammad O.

Interdisciplinary Biotechnology Unit, Aligarh Muslim University,

Aligarh-202002, India.

OBJECTIVES: The anticryptococcal activity of chloroquine was assessed

after incorporation in phosphatidylserine (PS)-containing negatively

charged liposomes in a murine model. METHODS: In the present study,

we investigated the antifungal activity of chloroquine entrapped in

PS liposomes against Cryptococcus neoformans in the macrophage cell

line J 774 and in a murine model. Mice were treated with free as well

as liposomal formulations of chloroquine before and after challenging

with C. neoformans infection. The anticryptococcal activity of

chloroquine was also evaluated in combination with fluconazole in the

treatment of systemic murine cryptococcosis. The efficacy of

chloroquine treatment was assessed by continued survival as well as

by colony forming units (cfu) in liver and brain of treated mice.

RESULTS: Chloroquine entrapped in PS liposomes shows increased

activity against C. neoformans infection both in in vitro and in vivo

studies. Moreover, the antifungal activity of fluconazole increases

when used in combination with liposomal chloroquine. Chloroquine in

PS liposomes was found to be more effective in comparison with the

same dose of free chloroquine or chloroquine entrapped in neutral

liposomes.

CONCLUSIONS: The enhanced anticryptococcal activity of chloroquine in

PS liposomes seems to be due to uptake of drug-containing PS

liposomes by macrophages. It can be assumed that liposome-mediated

delivery of chloroquine to macrophages results in an unfavourable

(alkaline) environment for the growth of C. neoformans inside

macrophages.

PMID: 15590713 [PubMed - in process]

PMID: 15648251 [PubMed - in process]

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And another full paper at:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?

cmd=Retrieve & db=pubmed & dopt=Abstract & list_uids=14688042