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Kang, Young‐Sook; Pardridge, William M.

doi:10.1023/a:1018982125649

Cited by 40 publications

(6 citation statements)

References 20 publications

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“…ingesting antigen-containing egg whites [71]. These facts support the idea that the novel avidin fusion proteins should not give rise to major immunological responses in vivo.…”

Section: The Potential Of Novel Avidin Fusion Proteins In Medical Tarsupporting

confidence: 64%

Avidin Fusion Protein Strategies in Targeted Drug and Gene Delivery

Laitinen¹,

Airenne²,

Räty³

et al. 2005

LDDD

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Chicken avidin is used in a wide variety of applications in the life sciences, due to its extraordinarily strong affinity for biotin. Avidin-biotin strategy has also recently established a role in medical targeting approaches for cancer treatments. An interesting new exploitation for avidin-biotin techniques is the utilization of this strong affinity in gene therapy, to target and enhance gene delivery to the appropriate target cells and tissues. In this communication, we review novel avidin fusion proteins that have been developed for enhanced gene delivery and drug targeting purposes. The principles of this approach are highlighted by the avidin fusion proteins Scavidin (fusion with the macrophage scavenger receptor class A), Lodavin (fusion with the endocytotic LDL receptor) and avidin-displaying baculovirus (Baavi). Scavidin and Lodavin are cell membrane proteins in which avidin is expressed as an extracellular portion, thereby enhancing the targeted drug and gene delivery with biotinylated drug molecules and vectors. Baavi, on the other hand, displays avidin moieties on its surface, and opens up possibilities for flexible modification of its targeting properties and other characteristics by using different biotin-conjugated molecules. Potential applications of avidin fusion proteins and future trends of targeted drug and gene delivery based on these strategies will be discussed.

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“…ingesting antigen-containing egg whites [71]. These facts support the idea that the novel avidin fusion proteins should not give rise to major immunological responses in vivo.…”

Section: The Potential Of Novel Avidin Fusion Proteins In Medical Tarsupporting

confidence: 64%

Avidin Fusion Protein Strategies in Targeted Drug and Gene Delivery

Laitinen¹,

Airenne²,

Räty³

et al. 2005

LDDD

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“…The brain volume of distribution (VD) of 1251-bio-PNA was determined from the ratio of dpm/g of brain divided by dpm/,tl of corresponding terminal plasma at 1 hr after injection. (17). In these experiments, 20 ,Ci of 1251-bio-PNA and 30 ,tg of OX26-SA conjugate were injected per rat.…”

Section: Methodsmentioning

confidence: 99%

Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo.

Pardridge

Boado

Kang

1995

Proc. Natl. Acad. Sci. U.S.A.

180

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Polyamide ("peptide") nucleic acids (PNAs) are molecules with antigene and antisense effects that may prove to be effective neuropharmaceuticals if these molecules are enabled to undergo transport through the brain capillary endothelial wall, which makes up the blood-brain barrier in vivo. The model PNA used in the present studies is an 18-mer that is antisense to the rev gene of human immunodeficiency virus type 1 and is biotinylated at the amino terminus and iodinated at a tyrosine residue near the carboxyl terminus. The biotinylated PNA was linked to a conjugate of streptavidin (SA) and the 0X26 murine monoclonal antibody to the rat transferrin receptor. The blood-brain barrier is endowed with high transferrin receptor concentrations, enabling the 0X26-SA conjugate to deliver the biotinylated PNA to the brain. Although the brain uptake of the free PNA was negligible following intravenous administration, the brain uptake of the PNA was increased at least 28-fold when the PNA was bound to the 0X26-SA vector. The brain uptake of the PNA bound to the 0X26-SA vector was 0.1% of the injected dose per gram of brain at 60 min after an intravenous injection, approximating the brain uptake of intravenously injected morphine. The PNA bound to the 0X26-SA vector retained the ability to bind to synthetic rev mRNA as shown by RNase protection assays. In summary, the present studies show that while the transport of PNAs across the blood-brain barrier is negligible, delivery of these potential neuropharmaceutical drugs to the brain may be achieved by coupling them to vector-mediated peptide-drug delivery systems.

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“… 21 Endocytic pathways are activated within the cells using a directing moiety or a ligand, which is used as a vector. 22 It has recently been shown that glutathione is coupled with micelles and nanoparticles and showed enormous potential in both targeting and enhancing the drug moieties into brain. 23 …”

Section: Introductionmentioning

confidence: 99%

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

Salem¹,

Ahmed²,

Hassaballah³

et al. 2015

DDDT

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BackgroundThe blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain.MethodsGlutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency.ResultsThe size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than −65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824.ConclusionOverall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections.

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Cited by 40 publications

References 20 publications

Avidin Fusion Protein Strategies in Targeted Drug and Gene Delivery

Avidin Fusion Protein Strategies in Targeted Drug and Gene Delivery

Vector-mediated delivery of a polyamide ("peptide") nucleic acid analogue through the blood-brain barrier in vivo.

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

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