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.
Highlights
The eye is made up of many components, and therapeutic agents could be applied to the anterior part of the eye
We recently developed an artificial virus, an LPD nanoparticle in combination with nuclear localization signaling (NLS) [61] peptide and transactivator of transcription (TAT) peptide [62], to produce efficient, cell-specific gene delivery to eye tissues, with sustained gene expression
We showed for the first time that LPD promotes efficient delivery in a cell specific-manner and long-term expression of the Retinal pigment epithelium protein 65 (Rpe65) gene in mice lacking Rpe65 protein, leading to in vivo correction of blindness [23]
Summary
The eye is made up of many components, and therapeutic agents could be applied to the anterior part of the eye. Intravitreal or subretinal routes are the only means of targeting agents to the posterior area of the eye. The eye is one of the sensory organs of the body, and frequent administration of drugs to the eye is undesirable. The eyes have been early targets for gene therapy because they are small—that is, they require relatively little active dose—they are self-contained, and because the tools of eye surgery have advanced enough to make these treatments possible. The eye offers an excellent target for gene therapy studies, it is accessible and relatively immune privileged. Most of the successful gene therapy trials use local administration of drug(s)/gene(s) into the eye
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