Overview and Characteristics Of Ophthalmic Nano Drug Delivery System
Most ophthalmic drugs are administered locally in the conjunctival sac, and the most commonly used dosage form is eye drops. Due to various physiological barriers, the eye bioavailability of eye drops is extremely low, generally less than 5%. On the one hand, the main reason is the rapid elimination rate of the drug on the ocular surface and short residence time. Most of the drugs instilled in the eye are lost quickly with the tears (partly absorbed by the conjunctiva and nasal mucosa into the systemic circulation), and partly bound by the contents of the tears or Decomposition; On the other hand, the absorption of the corneal route and the non-corneal route is restricted by the corneal barrier and the conjunctival barrier, respectively. Due to the low bioavailability of eye drops, sometimes in order to achieve the purpose of treatment, frequent and high-concentration administration is required, which leads to a decrease in patient compliance. And this increase also in the amount of drug absorbed through the conjunctiva and nasal mucosa, leading to systemic adverse reactions. In order to improve the ocular bioavailability of drugs, increase the therapeutic index, and reduce adverse reactions, pharmaceutical workers have done a lot of work on new ocular drug delivery systems, among which ophthalmic nano drug delivery systems have received much attention.
As early as the 1980s, nanotechnology began to be used in ophthalmology. In the early days, it was mainly used to improve the bioavailability of eye drops. At present, it is still focused on increasing bioavailability and controlled release administration. When the particle size of the drug reaches the nanometer level, the specific surface area of the drug is greatly increased, and the solubility and dissolution rate are increased accordingly. Many poorly soluble drugs can be prepared into suitable preparations. The drug-loaded nanoparticles have good adhesion, can adhere to the surface of the cornea and conjunctival epithelium, reduce the loss of precorneal drugs, increase the residence time of the particles on the ocular surface, and enable the effective release of drugs.
Chitosan and PEG are currently the most widely used microparticle surface modification materials. The surface of chitosan has a positive charge and has a strong affinity with the cornea, which can prolong the retention time of the nanoparticle on the ocular surface, improve the corneal permeability of the drug, and increase its bioavailability. Coating poly-ecaprolactone (PECL) nanocapsules with PEG and chitosan, and found that both PEG and chitosan promote drug penetration, and the transport mechanism is both transcellular pathways; but PEG can promote the drug to pass through the epithelial cell layer , And chitosan can keep the drug in the surface epithelial cells.
In addition, nanoparticles can control and delay drug release. Subconjunctival injection and intravitreal injection of drugs are effective ways to administer vitreoretinal diseases. They are used as invasive treatments to increase the duration of drug maintenance and reduce the number of administrations. The glucocorticoid budesonide polylactic acid nanoparticles were injected into the subconjunctiva of mice as a vascular endothelial growth factor inhibitor. Compared with the aqueous solution, the drug content in the lens on the first day was twice that of the latter; the third and seventh days The content in the retina was 9 times and 5.5 times the latter; on the 14th day, the retina, vitreous, cornea and lens were all significantly higher than the latter. Ganciclovir albumin nanoparticles were injected into the vitreous cavity. Two weeks later, it was found that the nanoparticles were mainly concentrated in the vitreous cavity and existed in a thin layer on the retina, near the blood-aqueous barrier area and in the ciliary body.
After injection of fluorescein-labeled polylactic acid (PLA) nanoparticles into the vitreous of an inflamed eye, the nanoparticles flow from the injection site to the vitreous cavity and quickly deposit on the inner limiting membrane. After 6 hours of injection, the drug penetrated into the inflammatory cells in the ciliary body. After 18-24 hours, the drug reached the inflammatory cells in the vitreous and retina. After 48 hours, the inflammation was significantly relieved. The nanoparticles gradually penetrate through the retina and localize to RPE cells, and fluorescein is released from the nanoparticles and diffuses to the retina and RPE cells. Therefore, the injection of PLA nanoparticles into the inflammatory vitreous can cross the retina and target RPE cells.
Compared with traditional ocular drug delivery systems, polymeric nanoparticles have certain advantages in many aspects such as bioavailability and drug release behavior. With the deepening of research, it has been discovered that the properties of nanoparticles can be further improved after modifying the nanoparticles with some high-molecular substances such as polysaccharides and other polymers. Therefore, in recent years, the research on the surface modification of drug-loaded nanoparticles has become an important link in the optimization process of ophthalmic nanoparticles.