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Recent advances in ocular drug delivery A) Encapsulated cell technology: - - Principle: Viable human cell lines are sequestrated in a porous implant that allows for diffusion of the proteins which these cells secret toward the target tissue Applications: Retinitis pigmentosa: cells secret ciliary neurotrophic factor "CNTF" Geographic atrophy in AMD B) Microspheres: - - Principle: Use of biodegradable polymers to suspend drugs into micro-particles or nano-particles Advantages: 1) Sustained drug release less frequent injections 2) Controlled drug release avoid burst effect Applications: 1) Pegaptanib 2) Triamcinolone acetonide C) Liposomes: - - Principle: Lipid vesicles used to encapsulate both hydrophilic & lipophilic drugs to be phagocytosed by target cells allowing target intra-cellular drug delivery ↓↓ toxicity Applications: 1) Amphotericin-B 2) Gentamicin D) Iontophoresis: - Principle: Non-surgical technique that utilizes an applicator to deliver weak electrical current to sclera to drive ionically charged drug molecules across sclera into choroid, retina & vetrious. E) Micro-cannulation into suprachoroidal space: - Applications: Triamcinolone injection F) Nano-technology: - - Principle: Creation and use of materials and devices at the size scale of intracellular structures and molecules, and involves systems and constructs in the order of <100 nm. General principles: 1- Bio-mimicry: direct molecules to the proper cells 2- Pseudo-intelligence 3- Feedback control: control dosage precisely at the single-cell level Applications: 1) Treatment of oxidative stress: Examples: AMD, DR, RP They scavenge reactive oxygen intermediates because the large surface area : volume ratio 2) Theragnostics: A process in which diagnosis of a disease state, individualized for a particular patient (even to particular cells within a patient), is coupled with therapy. - - - Nanopeptides are taken by diseased cells changing their gene expression, in ROP & AMD 3) Delivery of drugs, peptides, and genes: As mentioned before 4) Regenerative nanomedicine: Branch of medicine that deals with repairing or replacing tissues and organs by using advanced materials and methodologies. Regenerative nanomedicine uses nanoparticles containing gene transcription factors and other modulating molecules that allow reprogramming of cells in vivo. Examples: use of polyplexes to treat RP, replace damaged or dead retinal neurons in patients with chronic retinal detachment, RP, AMD, and allied diseases 5) Noninvasive biophysical measurement of IOP: Example: a wireless contact lens with an embedded sensor that measures changes in corneal curvature associated with changes in IOP