In vivo gene delivery into ocular tissues by eye drops of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) (PEO-PPO-PEO) polymeric micelles

Abstract

The primary objective of this study was to investigate the feasibility of using PEO-PPO-PEO non-ionic copolymeric micelles as a carrier for eye-drop gene delivery of plasmid DNA with lacZ gene in vivo. Using pyrene fluorescence probe methods, zeta potential, and dynamic light scattering test (DLS), the ability of micelle formation of these block copolymers with plasmid was studied. Gene expressions were visualized by both the quality of enzymatic color reaction using X-gal staining and by the quantification of the substrate chlorophenol red galactopyranoside (CPRG) in enucleated eyes on day 2 after gene transfer. In addition, microscopy to identify the types of cell showing uptake and expression of the transferred gene was used. We found that the block polymeric micelles were formed above 0.1% (w/v) of block copolymer with a size of 160 nm and a zeta potential

Single and mixed poloxamine micelles as nanocarriers for solubilization and sustained release of ethoxzolamide for topical glaucoma therapy

“…The core-shell structure may notably enhance the apparent aqueous solubility, leading to a greater concentration gradient favourable for diffusion, and also provide sustained release since the dilution factor in the lachrymal fluid is less than in other administration routes [16]. Polymeric micelles have been shown to be suitable ocular carriers for anti-inflammatory drugs [17] or even plasmids and genes [18,19]. Transcorneal permeation studies through excised rabbit cornea indicated that non-steroidal anti-inflammatory drug formulations in polymeric micelles can enhance about twofold drug permeation compared with that of an aqueous suspension of the same concentration because the dissolution step is overcome [17].…”

Ophthalmic light sensitive nanocarrier systems

“…The study revealed the ability of PEO-PPO-PEO polymeric micelles to deliver plasmid DNA with lacZ gene in vivo [26]. After topical administration three times a day for 2−3 days, enhanced gene expression was observed in the iris, sclera, conjunctiva and lateral muscle of rabbit eyes.…”

“…Currently, most light sensitive systems for drug and gene delivery are administered intravenously; however, techniques to administer PEO-PPO-PEO non-ionic copolymeric micelles through topical eye drops have shown promise in ocular tissues [26]. The study revealed the ability of PEO-PPO-PEO polymeric micelles to deliver plasmid DNA with lacZ gene in vivo [26].…”

“…After topical administration three times a day for 2−3 days, enhanced gene expression was observed in the iris, sclera, conjunctiva and lateral muscle of rabbit eyes. The copolymer micelle avoided degradation by the liver, prevented serum/protein interaction and displayed an increased half life (t ½ ) for potentially effective drug delivery [26]. Sensitizing PEO-PPO-PEO micelle systems to visible light and administering them intravenously rather than topically may improve the time interval between administration and localization while providing further control over gene release rates and site-directed expression at predefined periods of time.…”

Bioadhesive hyaluronan–chitosan nanoparticles can transport genes across the ocular mucosa and transfect ocular tissue

“…Despite the advances made in the gene delivery field, to our knowledge, there are no reports in the literature on the potential of nanoparticles, presented as liquid eye drops, for the transport of genes across the ocular barrier, although other synthetic vectors such as micelles and liposomes have shown a certain potential for this specific application. 40,41 Given the positive results obtained in the present work in terms of the ability of HA-CS nanoparticles to transfect differentiated cells and to enter the ocular epithelia, we further explored in vivo their potential in ocular gene therapy. Nanoparticles loaded with pEGFP or pbgal were administered onto the eye surface, and the cornea and conjunctiva were evaluated for gene expression.…”