Characterization of liposomal vesicles encapsulating rhodanese for cyanide antagonism

Petrikovics, Ilona; Budai, Marianna; Baskin, Steven I.; Rockwood, Gary A.; Childress, J.; Budai, Lívia; Gróf, Pál; Klebovich, Imre; Szilasi, Mária

doi:10.1080/10717540903003711

Cited by 21 publications

(14 citation statements)

References 43 publications

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“…The optimal liposome composition for the encapsulation of Rh was determined in earlier experiments to be the 60 : 40 ratio of POPC to Chol [19]. However, the prior experiments did not evaluate the DOPC or the cationic lipid DOTAP.…”

Section: Resultsmentioning

confidence: 99%

“…Unfortunately, the free Rh enzyme was rapidly destroyed by the body's immune system, which makes the efficacy of this approach quite limited. To overcome the limitations for the circulating free Rh, micro- or nanosized carrier systems among others sterically stabilized unilamellar liposomes of ~100–150 nm diameter are in the focus of recent encapsulation efforts [19]. The encapsulation of Rh with a sulfur compound into liposomes—the so-called coencapsulation—can offer further advantages.…”

Section: Introductionmentioning

confidence: 99%

“…The lipid composition has a significant impact on the encapsulation efficiency of the Rh and/or sulfur compound and on the in vivo stability and antidotal effect of the carrier system [19]. Thus, optimization of the liposomal composition is an inevitable step in the design of novel antidotal systems.…”

Section: Introductionmentioning

confidence: 99%

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Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, andIn VivoEfficacy Studies on Mice to Antagonize Cyanide Intoxication

Petrikovics

Jayanna

Childress

et al. 2011

Journal of Drug Delivery

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Present studies have focused on a novel cyanide antidotal system, on the coencapsulation of a new sulfur donor DTO with rhodanese within sterically stabilized liposomes. The optimal lipid composition for coencapsulation of DTO with rhodanese is the combination of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, cationic lipid (DOTAP), and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] ammonium salt (with molar ratios of 82.7 : 9.2 : 3.0 : 5.1). With the optimized compositions, prophylactic and therapeutic in vivo efficacy studies were carried out in a mice model. When DTO was coencapsulated with rhodanese and thiosulfate the prophylactic antidotal protection was 4.9 × LD50. Maximum antidotal protection against cyanide intoxication (15 × LD50) was achieved with coencapsulated rhodanese and DTO/thiosulfate in combination with sodium nitrite. When applied therapeutically, 100% survival rate (6/6) was achieved at 20 mg/kg cyanide doses with the encapsulated DTO-rhodanese-thiosulfate antidotal systems with and without sodium nitrite. These data are indicating that the appropriately formulated DTO is a promising sulfur donor for cyanide antagonism.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, andIn VivoEfficacy Studies on Mice to Antagonize Cyanide Intoxication

Petrikovics

Jayanna

Childress

et al. 2011

Journal of Drug Delivery

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“…Once ionized, the drugs are no longer able to pass through the hydrophobic membrane (Figure 1). Liposomes with encapsulated enzymes have also been studied as detoxifiers [38,39]. Organophosphates and cyanide toxins penetrated the bilayer and were degraded by encapsulated enzymes within the core.…”

Section: Nanomaterials Used As Detoxifying Agentsmentioning

confidence: 99%

Nanodetoxification: Emerging Role of Nanomaterials in Drug Intoxication Treatment

2011

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Treatment for intoxication involves the neutralization or clearance of a toxic compound, but the current methods of treatment are limited in their ability to safely and effectively detoxify the patient. Emerging research has focused on using nanoparticles as parenteral detoxifying agents to circulate through the body and capture toxins. The variable compositions of these nanoparticles control the mechanism in which they capture and remove specific compounds. As discussed in this article, the recent methods for utilizing nanoparticles for detoxification show great potential for intoxication treatment. However, several challenges must be overcome before a universal nanoparticle detoxification method is available for clinical use.

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“…Recently, several studies explored with success the path of liposomes for the administration of different peptides (7,11,12). Liposomes, spherical structures composed of one or several phospholipid bilayers, possess many attractive characteristics to stabilize peptidic drugs and to improve their pharmacological properties.…”

Section: Introductionmentioning

confidence: 99%

The Experimental Design as Practical Approach to Develop and Optimize a Formulation of Peptide-Loaded Liposomes

et al. 2010

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Abstract. To investigate the encapsulation of Print 3G, a peptidic agent that could reduce the angiogenic development of breast tumors, pegylated liposomes used as intravenous vectors were studied and characterized. Recently, the path of liposomes has been explored with success to improve the pharmacological properties of peptidic drugs and to stabilize them. In this study, loaded unilamellar vesicles composed of SPC:CHOL:mPEG2000-DSPE (47:47:6) were prepared by the hydration of lipid film technique. An HPLC method was developed and validated for the determination of Print 3G to calculate its encapsulation efficiency. Observed Print 3G adsorption on different materials employed during liposome preparation (such as glass beads, tubing, and connections for extrusion) led to the modification of the manufacturing method. The freeze-thawing technique was used to enhance the amount of Print 3G encapsulated into blank liposomes prepared using the hydration of lipid film procedure. Many factors may influence peptide entrapment, namely the number of freeze-thawing cycles, the lipid concentration, the peptide concentration, and the mixing time. Consequently, a design of experiments was performed to obtain the best encapsulation efficiency while minimizing the number of experiments. The lipid concentration and the number of freeze-thawing cycles were identified as the positive factors influencing the encapsulation. As a result of the optimization, an optimum was found and encapsulation efficiencies were improved from around 30% to 63%. Liposome integrity was evaluated by photon correlation spectroscopy and freeze-fracture electron microscopy to ensure that the selected formulation possesses the required properties to be a potential candidate for further in vitro and in vivo experiments.

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Characterization of liposomal vesicles encapsulating rhodanese for cyanide antagonism

Cited by 21 publications

References 43 publications

Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, andIn VivoEfficacy Studies on Mice to Antagonize Cyanide Intoxication

Optimization of Liposomal Lipid Composition for a New, Reactive Sulfur Donor, andIn VivoEfficacy Studies on Mice to Antagonize Cyanide Intoxication

Nanodetoxification: Emerging Role of Nanomaterials in Drug Intoxication Treatment

The Experimental Design as Practical Approach to Develop and Optimize a Formulation of Peptide-Loaded Liposomes

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