Factors associated with the performance of carrier erythrocytes obtained by hypotonic dialysis

Millán, Carmen Gutiérrez; Castañeda, Aránzazu Zarzuelo; Marinero, M. Luisa Sayalero; Lanao, José M.

doi:10.1016/j.bcmd.2004.06.004

Cited by 58 publications

(24 citation statements)

References 52 publications

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“…Erythrocyte ghost preparations have been described previously for studying the erythrocyte membrane and cytoskeleton and malarial infection [33–38]. However, malarial infection rates of earlier ghosts were either untested or lower than in normal erythrocytes.…”

Section: Resultsmentioning

confidence: 99%

Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy

et al. 2006

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BackgroundMalaria remains a serious health problem because resistance develops to all currently used drugs when their parasite targets mutate. Novel antimalarial drug targets are urgently needed to reduce global morbidity and mortality. Our prior results suggested that inhibiting erythrocyte Gs signaling blocked invasion by the human malaria parasite Plasmodium falciparum. Methods and FindingsWe investigated the erythrocyte guanine nucleotide regulatory protein Gs as a novel antimalarial target. Erythrocyte “ghosts” loaded with a Gs peptide designed to block Gs interaction with its receptors, were blocked in β-adrenergic agonist-induced signaling. This finding directly demonstrates that erythrocyte Gs is functional and that propranolol, an antagonist of G protein–coupled β-adrenergic receptors, dampens Gs activity in erythrocytes. We subsequently used the ghost system to directly link inhibition of host Gs to parasite entry. In addition, we discovered that ghosts loaded with the peptide were inhibited in intracellular parasite maturation. Propranolol also inhibited blood-stage parasite growth, as did other β2-antagonists. β-blocker growth inhibition appeared to be due to delay in the terminal schizont stage. When used in combination with existing antimalarials in cell culture, propranolol reduced the 50% and 90% inhibitory concentrations for existing drugs against P. falciparum by 5- to 10-fold and was also effective in reducing drug dose in animal models of infection.ConclusionsTogether these data establish that, in addition to invasion, erythrocyte G protein signaling is needed for intracellular parasite proliferation and thus may present a novel antimalarial target. The results provide proof of the concept that erythrocyte Gs antagonism offers a novel strategy to fight infection and that it has potential to be used to develop combination therapies with existing antimalarials.

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Section: Resultsmentioning

confidence: 99%

Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy

et al. 2006

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“…Erythrocyte-based delivery of new and conventional drugs is thus experiencing increasing interests in drug delivery and in managing complex pathologies, especially when side effects could become serious issues [13], [19], [30]. Recently, erythrocytes have been used to encapsulate the antibiotic amikacin, and a sustained release from loaded erythrocytes over a 48 hours period was demonstrated, suggesting a potential use of the erythrocytes as a slow systemic-release system for antibiotics.…”

Section: Discussionmentioning

confidence: 99%

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

et al. 2011

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Cytotoxic chemotherapy of cancer is limited by serious, sometimes life-threatening, side effects that arise from toxicities to sensitive normal cells because the therapies are not selective for malignant cells. So how can they be selectively improved? Alternative pharmaceutical formulations of anti-cancer agents have been investigated in order to improve conventional chemotherapy treatment. These formulations are associated with problems like severe toxic side effects on healthy organs, drug resistance and limited access of the drug to the tumor sites suggested the need to focus on site-specific controlled drug delivery systems. In response to these concerns, we have developed a new drug delivery system based on magnetic erythrocytes engineered with a viral spike fusion protein. This new erythrocyte-based drug delivery system has the potential for magnetic-controlled site-specific localization and highly efficient fusion capability with the targeted cells. Here we show that the erythro-magneto-HA virosomes drug delivery system is able to attach and fuse with the target cells and to efficiently release therapeutic compounds inside the cells. The efficacy of the anti-cancer drug employed is increased and the dose required is 10 time less than that needed with conventional therapy.

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“…To determine the effect of drug concentration on loading efficiency we use different drug concentrations (2 mg, 4 mg, 8 mg, and 10 mg) for all selected incubation times, and compare results to obtain the more suitable concentration for loading process which produce most excellent loading parameters 23.…”

Section: Methodsmentioning

confidence: 99%

Characterization of Human Erythrocytes as Potential Carrier for Pravastatin: An In Vitro Study

Harisa¹,

Ibrahim²,

Alanazi³

2011

Int. J. Med. Sci.

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Drug delivery systems including chemical, physical and biological agents that enhance the bioavailability, improve pharmacokinetics and reduce toxicities of the drugs. Carrier erythrocytes are one of the most promising biological drug delivery systems investigated in recent decades. The bioavailability of statin drugs is low due the effects of P-glycoprotein in the gastro-intestinal tract as well as the first-pass metabolism. Therefore in this work we study the effect of time, temperature as well as concentration on the loading of pravastatin in human erythrocytes to be using them as systemic sustained release delivery system for this drug. After the loading process is performed the carriers' erythrocytes were physically and cellulary characterized. Also, the in vitro release of pravastatin from carrier erythrocytes was studied over time interval. Our results revealed that, human erythrocytes have been successfully loaded with pravastatin using endocytosis method either at 25oC or at 37oC. The loaded amount at 10 mg/ml is 0.32mg/0.1 ml and 0.69 mg/0.1 ml. Entrapment efficiency is 34% and 94% at 25oC and 37oC respectively at drug concentration 4 mg/ml. Moreover the percent of cells recovery is 87-93%. Hematological parameters and osmotic fragility behavior of pravastatin loaded erythrocytes were similar that of native erythrocytes. Scanning electron microscopy demonstrated that the pravastatin loaded cells has no change in the morphology. Pravastatin releasing from carrier cell was 83% after 23 hours in phosphate buffer saline and decreased to 72% by treatment of carrier cells with glutaraldehyde. The releasing pattern of the drug from loaded erythrocytes obeyed first order kinetics. It concluded that pravastatin is successfully entrapped into erythrocytes with acceptable loading parameters and moderate morphological changes, this suggesting that erythrocytes can be used as prolonged release for pravastatin.

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Factors associated with the performance of carrier erythrocytes obtained by hypotonic dialysis

Cited by 58 publications

References 52 publications

Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy

Erythrocyte G Protein as a Novel Target for Malarial Chemotherapy

Newly Engineered Magnetic Erythrocytes for Sustained and Targeted Delivery of Anti-Cancer Therapeutic Compounds

Characterization of Human Erythrocytes as Potential Carrier for Pravastatin: An In Vitro Study

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