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Lipid Nanoparticles for Ocular Gene Delivery.

Wang Y, Rajala A, Rajala RV - J Funct Biomater (2015)

Bottom Line: LPD nanoparticles are used to target the retina.There have also been promising results achieved recently with LPD nanoparticles to deliver functional genes and micro RNA to treat retinal diseases.Here, we review recent advances in ocular drug and gene delivery employing lipid nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: Dean A. McGee Eye Institute, Oklahoma City, OK 73104, USA. yuhong-wang@ouhsc.edu.

ABSTRACT
Lipids contain hydrocarbons and are the building blocks of cells. Lipids can naturally form themselves into nano-films and nano-structures, micelles, reverse micelles, and liposomes. Micelles or reverse micelles are monolayer structures, whereas liposomes are bilayer structures. Liposomes have been recognized as carriers for drug delivery. Solid lipid nanoparticles and lipoplex (liposome-polycation-DNA complex), also called lipid nanoparticles, are currently used to deliver drugs and genes to ocular tissues. A solid lipid nanoparticle (SLN) is typically spherical, and possesses a solid lipid core matrix that can solubilize lipophilic molecules. The lipid nanoparticle, called the liposome protamine/DNA lipoplex (LPD), is electrostatically assembled from cationic liposomes and an anionic protamine-DNA complex. The LPD nanoparticles contain a highly condensed DNA core surrounded by lipid bilayers. SLNs are extensively used to deliver drugs to the cornea. LPD nanoparticles are used to target the retina. Age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy are the most common retinal diseases in humans. There have also been promising results achieved recently with LPD nanoparticles to deliver functional genes and micro RNA to treat retinal diseases. Here, we review recent advances in ocular drug and gene delivery employing lipid nanoparticles.

No MeSH data available.


Related in: MedlinePlus

LPD-mediated gene delivery into the retina. Schematic illustration of the eye and route of administration. The most commonly used and preferred mode of administration to retinal layers is subretinal (A). Generation of green fluorescent protein construct under the control of CMV promoter (B). CMV, cytomegalovirus; GFP, green fluorescent protein; WRE, posttranscriptional regulatory element from the woodchuck hepatitis virus; PolyA, polyadenylation sequence; increases the stability of the molecule. Using BalbC mice, we injected the cDNA construct subretinally into one eye. LPD was complexed with CMV-GFP-WRE-PolyA construct. The other eye was injected with LPD, with a control vector without GFP. Seventy-two hours later, eyes were removed and examined for GFP expression under inverted fluorescence microscopy. GFP expression is clearly seen in the GFP-injected eye (E), but not in the control eye (C). Whole RPE flat mounts were prepared and examined for GFP expression under inverted fluorescence microscopy. GFP expression is seen in the GFP-injected eye (F), but not in the control eye (D). Scale bar, 20 µm.
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jfb-06-00379-f002: LPD-mediated gene delivery into the retina. Schematic illustration of the eye and route of administration. The most commonly used and preferred mode of administration to retinal layers is subretinal (A). Generation of green fluorescent protein construct under the control of CMV promoter (B). CMV, cytomegalovirus; GFP, green fluorescent protein; WRE, posttranscriptional regulatory element from the woodchuck hepatitis virus; PolyA, polyadenylation sequence; increases the stability of the molecule. Using BalbC mice, we injected the cDNA construct subretinally into one eye. LPD was complexed with CMV-GFP-WRE-PolyA construct. The other eye was injected with LPD, with a control vector without GFP. Seventy-two hours later, eyes were removed and examined for GFP expression under inverted fluorescence microscopy. GFP expression is clearly seen in the GFP-injected eye (E), but not in the control eye (C). Whole RPE flat mounts were prepared and examined for GFP expression under inverted fluorescence microscopy. GFP expression is seen in the GFP-injected eye (F), but not in the control eye (D). Scale bar, 20 µm.

Mentions: DNA packed into liposomes must overcome biological barriers before it can be integrated into the genome. These barriers are the cellular membrane, the nuclear membrane, and chromosomal integrity. Cell targeting and cell-internalization peptides have been extensively studied and used for efficient drug delivery and for image analysis [61]. Arginine-rich (RNA-binding, DNA-binding, and polyarginine) cell-permeable peptides have been shown to cross the cellular barrier [62]. Nuclear localization peptide of the SV40 T large antigen has been shown to promote high LPD-mediated transfection efficiency [23,24,61,78]. In designing our recently formulated lipid nanoparticle, we used a nuclear localization peptide derived from SV40 T antigen (DKKKRKVDKKKRKVDKKKRKV), and another peptide derived from human immunodeficiency virus transactivator of transcription (TAT; YGRKKRRQRRR) peptide [79,80,81,82]. The TAT-fusions have been shown to cross the blood–brain barrier [81]. A combination of these two peptides resulted in a high level of sustained gene expression in vivo (Figure 2) [23]. The TAT-peptide belongs to an arginine-rich family of peptides, which is an abundant source of membrane-permeable peptides that have potential as carriers for intracellular protein delivery [54,67]. Even with the omission of TAT-peptide, LPD nanoparticles were able to mediate gene delivery [24].


Lipid Nanoparticles for Ocular Gene Delivery.

Wang Y, Rajala A, Rajala RV - J Funct Biomater (2015)

LPD-mediated gene delivery into the retina. Schematic illustration of the eye and route of administration. The most commonly used and preferred mode of administration to retinal layers is subretinal (A). Generation of green fluorescent protein construct under the control of CMV promoter (B). CMV, cytomegalovirus; GFP, green fluorescent protein; WRE, posttranscriptional regulatory element from the woodchuck hepatitis virus; PolyA, polyadenylation sequence; increases the stability of the molecule. Using BalbC mice, we injected the cDNA construct subretinally into one eye. LPD was complexed with CMV-GFP-WRE-PolyA construct. The other eye was injected with LPD, with a control vector without GFP. Seventy-two hours later, eyes were removed and examined for GFP expression under inverted fluorescence microscopy. GFP expression is clearly seen in the GFP-injected eye (E), but not in the control eye (C). Whole RPE flat mounts were prepared and examined for GFP expression under inverted fluorescence microscopy. GFP expression is seen in the GFP-injected eye (F), but not in the control eye (D). Scale bar, 20 µm.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493518&req=5

jfb-06-00379-f002: LPD-mediated gene delivery into the retina. Schematic illustration of the eye and route of administration. The most commonly used and preferred mode of administration to retinal layers is subretinal (A). Generation of green fluorescent protein construct under the control of CMV promoter (B). CMV, cytomegalovirus; GFP, green fluorescent protein; WRE, posttranscriptional regulatory element from the woodchuck hepatitis virus; PolyA, polyadenylation sequence; increases the stability of the molecule. Using BalbC mice, we injected the cDNA construct subretinally into one eye. LPD was complexed with CMV-GFP-WRE-PolyA construct. The other eye was injected with LPD, with a control vector without GFP. Seventy-two hours later, eyes were removed and examined for GFP expression under inverted fluorescence microscopy. GFP expression is clearly seen in the GFP-injected eye (E), but not in the control eye (C). Whole RPE flat mounts were prepared and examined for GFP expression under inverted fluorescence microscopy. GFP expression is seen in the GFP-injected eye (F), but not in the control eye (D). Scale bar, 20 µm.
Mentions: DNA packed into liposomes must overcome biological barriers before it can be integrated into the genome. These barriers are the cellular membrane, the nuclear membrane, and chromosomal integrity. Cell targeting and cell-internalization peptides have been extensively studied and used for efficient drug delivery and for image analysis [61]. Arginine-rich (RNA-binding, DNA-binding, and polyarginine) cell-permeable peptides have been shown to cross the cellular barrier [62]. Nuclear localization peptide of the SV40 T large antigen has been shown to promote high LPD-mediated transfection efficiency [23,24,61,78]. In designing our recently formulated lipid nanoparticle, we used a nuclear localization peptide derived from SV40 T antigen (DKKKRKVDKKKRKVDKKKRKV), and another peptide derived from human immunodeficiency virus transactivator of transcription (TAT; YGRKKRRQRRR) peptide [79,80,81,82]. The TAT-fusions have been shown to cross the blood–brain barrier [81]. A combination of these two peptides resulted in a high level of sustained gene expression in vivo (Figure 2) [23]. The TAT-peptide belongs to an arginine-rich family of peptides, which is an abundant source of membrane-permeable peptides that have potential as carriers for intracellular protein delivery [54,67]. Even with the omission of TAT-peptide, LPD nanoparticles were able to mediate gene delivery [24].

Bottom Line: LPD nanoparticles are used to target the retina.There have also been promising results achieved recently with LPD nanoparticles to deliver functional genes and micro RNA to treat retinal diseases.Here, we review recent advances in ocular drug and gene delivery employing lipid nanoparticles.

View Article: PubMed Central - PubMed

Affiliation: Dean A. McGee Eye Institute, Oklahoma City, OK 73104, USA. yuhong-wang@ouhsc.edu.

ABSTRACT
Lipids contain hydrocarbons and are the building blocks of cells. Lipids can naturally form themselves into nano-films and nano-structures, micelles, reverse micelles, and liposomes. Micelles or reverse micelles are monolayer structures, whereas liposomes are bilayer structures. Liposomes have been recognized as carriers for drug delivery. Solid lipid nanoparticles and lipoplex (liposome-polycation-DNA complex), also called lipid nanoparticles, are currently used to deliver drugs and genes to ocular tissues. A solid lipid nanoparticle (SLN) is typically spherical, and possesses a solid lipid core matrix that can solubilize lipophilic molecules. The lipid nanoparticle, called the liposome protamine/DNA lipoplex (LPD), is electrostatically assembled from cationic liposomes and an anionic protamine-DNA complex. The LPD nanoparticles contain a highly condensed DNA core surrounded by lipid bilayers. SLNs are extensively used to deliver drugs to the cornea. LPD nanoparticles are used to target the retina. Age-related macular degeneration, retinitis pigmentosa, and diabetic retinopathy are the most common retinal diseases in humans. There have also been promising results achieved recently with LPD nanoparticles to deliver functional genes and micro RNA to treat retinal diseases. Here, we review recent advances in ocular drug and gene delivery employing lipid nanoparticles.

No MeSH data available.


Related in: MedlinePlus