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Lipid Nanoparticles for Ocular Gene Delivery.

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

Bottom Line: 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.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

Lipid, peptide, and protein components of the lipid nanoparticle. The monolayer structures are called micelles, whereas the lipid bilayer structures are called liposomes (A). Chemical structures of DOTAP (B), DOPE (C), and Cholesterol (D). NLS (E) and TAT (F) peptide sequences and protamine (small, arginine-rich, nuclear protein) (G) are also presented. DOTAP, 1, 2-dioleoyl-3-trimethylammonium-propane, DOPE, 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine; NLS, nuclear localization signal; TAT, transactivator of transcription. Formulation of a peptide-based lipid nanoparticle (H). Peptide-based nanoparticles can be formulated by mixing liposome, protamine, DNA, TAT, and NLS. TAT, transactivator of transcription; NLS, nuclear localization signal.
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jfb-06-00379-f001: Lipid, peptide, and protein components of the lipid nanoparticle. The monolayer structures are called micelles, whereas the lipid bilayer structures are called liposomes (A). Chemical structures of DOTAP (B), DOPE (C), and Cholesterol (D). NLS (E) and TAT (F) peptide sequences and protamine (small, arginine-rich, nuclear protein) (G) are also presented. DOTAP, 1, 2-dioleoyl-3-trimethylammonium-propane, DOPE, 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine; NLS, nuclear localization signal; TAT, transactivator of transcription. Formulation of a peptide-based lipid nanoparticle (H). Peptide-based nanoparticles can be formulated by mixing liposome, protamine, DNA, TAT, and NLS. TAT, transactivator of transcription; NLS, nuclear localization signal.

Mentions: The main constituent of lipid nanoparticles is the liposome. A liposome is a spherical vesicle of a lamellar phase of the lipid bilayer. The liposome can be used as a transport vehicle to send nutrients and drugs into the body [45,46,47]. One can prepare these liposomes through disruption of biological membranes by sonication, a process of sending sound waves to disturb particles in a solution. Lipids can naturally form themselves into nano-films and nano-structures, called micelles, reverse micelles, and liposomes [20,48]. The monolayer structures are called micelles or reverse micelles, whereas the lipid bilayer structures are called liposomes (Figure 1A). In the lipid bilayer, phospholipids are principal lipids, which are amphiphilic molecules with hydrophilic (water-loving, polar) and lipophilic (fat-loving) properties, sometimes described as having hydrophobic tails and hydrophilic heads. Therefore, liposomes are artificial phospholipid bilayers; as a result, liposomes have biocompatible characteristics [49,50]. This biocompatibility accounts for their most important advantages as drug carriers, (1) liposomes have almost no toxicity and low antigenicity; (2) liposomes can be biodegraded and metabolized in vivo, and (3) liposomal properties, such as membrane permeability, can be controlled to some extent [51,52,53]. Remarkably, liposomes can entrap and protect drug molecules or nucleic acids on the journey to the target site [54].


Lipid Nanoparticles for Ocular Gene Delivery.

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

Lipid, peptide, and protein components of the lipid nanoparticle. The monolayer structures are called micelles, whereas the lipid bilayer structures are called liposomes (A). Chemical structures of DOTAP (B), DOPE (C), and Cholesterol (D). NLS (E) and TAT (F) peptide sequences and protamine (small, arginine-rich, nuclear protein) (G) are also presented. DOTAP, 1, 2-dioleoyl-3-trimethylammonium-propane, DOPE, 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine; NLS, nuclear localization signal; TAT, transactivator of transcription. Formulation of a peptide-based lipid nanoparticle (H). Peptide-based nanoparticles can be formulated by mixing liposome, protamine, DNA, TAT, and NLS. TAT, transactivator of transcription; NLS, nuclear localization signal.
© Copyright Policy
Related In: Results  -  Collection

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

jfb-06-00379-f001: Lipid, peptide, and protein components of the lipid nanoparticle. The monolayer structures are called micelles, whereas the lipid bilayer structures are called liposomes (A). Chemical structures of DOTAP (B), DOPE (C), and Cholesterol (D). NLS (E) and TAT (F) peptide sequences and protamine (small, arginine-rich, nuclear protein) (G) are also presented. DOTAP, 1, 2-dioleoyl-3-trimethylammonium-propane, DOPE, 1, 2-dioleoyl-sn-glycero-3-phosphoethanolamine; NLS, nuclear localization signal; TAT, transactivator of transcription. Formulation of a peptide-based lipid nanoparticle (H). Peptide-based nanoparticles can be formulated by mixing liposome, protamine, DNA, TAT, and NLS. TAT, transactivator of transcription; NLS, nuclear localization signal.
Mentions: The main constituent of lipid nanoparticles is the liposome. A liposome is a spherical vesicle of a lamellar phase of the lipid bilayer. The liposome can be used as a transport vehicle to send nutrients and drugs into the body [45,46,47]. One can prepare these liposomes through disruption of biological membranes by sonication, a process of sending sound waves to disturb particles in a solution. Lipids can naturally form themselves into nano-films and nano-structures, called micelles, reverse micelles, and liposomes [20,48]. The monolayer structures are called micelles or reverse micelles, whereas the lipid bilayer structures are called liposomes (Figure 1A). In the lipid bilayer, phospholipids are principal lipids, which are amphiphilic molecules with hydrophilic (water-loving, polar) and lipophilic (fat-loving) properties, sometimes described as having hydrophobic tails and hydrophilic heads. Therefore, liposomes are artificial phospholipid bilayers; as a result, liposomes have biocompatible characteristics [49,50]. This biocompatibility accounts for their most important advantages as drug carriers, (1) liposomes have almost no toxicity and low antigenicity; (2) liposomes can be biodegraded and metabolized in vivo, and (3) liposomal properties, such as membrane permeability, can be controlled to some extent [51,52,53]. Remarkably, liposomes can entrap and protect drug molecules or nucleic acids on the journey to the target site [54].

Bottom Line: 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.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