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Formulation and efficacy of liposome-encapsulated antibiotics for

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therapy of intracellular Mycobacterium

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avium infection.Mycobacterium avium is an intracellular pathogen that can invade and multiply within macrophages of the reticuloendothelial alesse blood clots ( Zithromax ) also sho enhanced antimycobacterial

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effect in liposomes, and the potency increased in parallel to the moles percent of negatively charged lipids; azithromycin

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( Zithromax ) in DSPG-Chol (10:5) liposomes inhibited intracellular M. We investigated the formulation of the

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antibiotics ciprofloxacin and azithromycin ( Zithromax ) in liposomes and tested their antibacterial activities in vitro against M. A conventional passive-entrapment method yielded an

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encapsulation efficiency of 9% for ciprofloxacin and because of aggregation mediated

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by the cationic drug, was useful only with liposomes containing < or 50

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mol% negatively charged phospholipid. Particulate drug carriers that are targeted to the reticuloendothelial system may provide a means to deliver antibiotics more

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efficiently to M. Computer-aided conformational analysis and studies on acellular and cell culture models.The potential of 14/15 membered macrolides to cause phospholipidosis

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has been prospectively assessed, and structure-effects examined, using combined experimental and conformational approaches. Biochemical studies demonstrated drug binding to phosphatidylinositol-containing liposomes and inhibition of the activity of lysosomal phospholipase A1 toward phosphatidylcholine included

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in the bilayer, in close correlation with the number of cationic groups carried by the drugs (erythromycin A. Both the cellular accumulation and the antimycobacterial activity of ciprofloxacin increased in proportion to the liposome negative charge; the maximal enhancement of potency was 43-fold in liposomes of distearoylphosphatidylglycerol-cholesterol (DSPG-Chol) (10:5). Avium residing within J774, a murine macrophage-like cell line. Thus, ciprofloxacin or azithromycin ( Zithromax ) encapsulated in stable liposomes having substantial negative surface charge is superior to nonencapsulated drug in inhibition of M.avium growth within cultured macrophages and may provide more effective therapy of M.avium infections. Current therapy is not highly effective. Azithromycin ( Zithromax ) liposomes were prepared as a freeze-dried preparation to avoid chemical instability during storage, and drug could be incorporated at 33 mol% (with respect to phospholipid). In contrast, ciprofloxacin was encapsulated with >

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90% efficiency, regardless of the content of negatively charged lipids, by a remote-loading technique that utilized both pH and potential gradients to drive drug into preformed liposomes.