PLGA nanoparticles in the ocular drug delivery
The topical ocular administration of drugs has two different purposes: to treat superficial eye diseases, such as infections (e.g. conjunctivitis, blepharitis, keratitis sicca) and to provide intraocular treatment through the cornea for diseases such as glaucoma or uveitis.Compared with drug delivery to other parts of the body, ocular drug delivery has met with significant challenges posed by various ocular barriers. Ocular drug delivery efficiency depends on the barriers and the clearance from the choroidal, conjunctival vessels and lymphatic. Traditional drug administration reduces the clinical efficacy especially for poor water soluble molecules and for the posterior segment of the eye. They typically provide low bioavailability (less than 5%) owing to poor pre-corneal retention and penetration. The factors affecting pre-corneal retention include rapid tear turnover, blinking, and solution drainage, which result in the loss of drug after topical administration. Therefore, frequent instillations of eye drops are required to maintain a therapeutic drug level on the pre-corneal surface. Frequent use of concentrated eye drops can induce toxicity, corneal dryness and possible severe systemic side effects[1, 2].
In different studies has been evaluatedthe suitability and feasibility of PLGA nanoparticles (~200 nm) as suitable for ophthalmic administration such as the ocular delivery of Flurbiprofen, Moxifloxacin, Aceclofenac, loteprednol etabonate,Bevacizumab, Tacrolimus,Dexamethasone acetate, Sparfloxacin[3-13].
Proprierties of PLGA NPs for ocular delivery:
- Nanoparticles (NPs) with size range from 10nm to 1000nm improved topical passage of large, poorly water-soluble molecules through the barriers of ocular system.
- Surface modifications of PLGA nanoparticles was done to increase the PLGA nanoparticles propierties for ocular drug delivery. Chitosan-coated PLGA NPs improve the mucoadhesion ability and the drug release properties. Chitosan adheres to mucus layers in vivo, via electrostatic interactions between the positively charged amino groups within chitosan, and the negatively charged sialic groups of mucin [9, 15].PEG-coated PLGA nanoparticles was found to be significantly greater for bioadhesion, bioretention, and susteined/prolonged pharmacologic effect in the rat’s eyes.
- Positive and negatively charged NPs were shown to distribute to the inner ocular tissues such as retina and vitreous humor following application of iontophoresis technique. Positively charged NPs have shown higher penetration than negatively charged NPs . For topical administration, positively charged polymeric materials on the other hand, may allow more prolonged retention on the eye surface. Following intravitreal injection, anionic NPs were shown to distribute to the subretinal space .
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