Oculis patent protected technology is the result of 20+ years of academic research by Dr. Thorsteinn Loftsson, Dr. Einar Stefansson and co-workers. The emphasis has been on the effect cyclodextrin has on transfer of drugs across biological membranes and the use of cyclodextrin for eye formulations. Cyclodextrins are cyclic oligosaccharides with hydrophilic outer surface but slightly lipophilic inner surface. Cyclodextrins form water soluble complexes with many lipophilic and poorly water-soluble drugs.
Oculis has thoroughly investigated how cyclodextrin facilitate the transport of drugs through biological membranes, i.e. in which case they are of use and when they are not. Oculis has also investigated how cyclodextrin improve the transport of drugs from the surface into the posterior part of the eye. Cyclodextrin are already used for variety of approved drugs and food products.
Oculis discovered how cyclodextrin complexes can form nano-particles in aqueous solution. The diameter of the nano-particles is about 100 nm. Oculis has investigated the effects of cyclodextrin nano-particles on transfer of drugs, e.g. dexamethasone and dorzolamide, from the surface of the eye into both anterior and posterior part of the eye.
The next step was to use the nanoparticles to form microparticles with limited water solubility (see figure). The microparticles form micro suspension particle diameter of 2 micrometers (2000 nm). The particles adhere to conjunctiva where they dissolve slowly to form nanoparticles with diameter of 100 nm. These nanoparticles carry the drug to cornea, conjunctiva and sclera as they dissolve into single complexes and release the drug. For the production Oculis uses gamma-cyclodextrin (γCD) which has GRAS (generally recognized as safe) recognition in food and drug industry. Other raw materials are excipients generally recognized for pharmaceutics and listed in pharmacopeias like Ph. Eur.
Microparticles adhere to the mucus on the surface of the eye and dissolve gradually and gradually release dissolved drug. Normally the half-life (t½) for a drug from a conventional eye drop on the surface of the eye is between 1 and 3 minutes. The half-life of a drug in the cyclodextrin microparticles can be between 1 and 3 hours or more and drug is still present in the tear film 6 hours after administration of a nanoparticle eye drop. .
The image shows schematic formation of a single complex of drug and cyclodextrin which gradually forms water soluble nano-particle and finally a bigger micro-particle. This is a reversible formation
The Oculis’ nanoparticle technology:
- Is able to solubilize large doses of lipophilic drugs in aqueous solutions without the use of organic co-solvents or surfactants.
- Maintains sustained high concentrations of dissolved drug in the aqueous tear fluid.
- Enhances drug delivery to the anterior and/or posterior segment of the eye, and enables topical delivery of ophthalmic drugs that currently are, for example, administered via intravitreal injections.
- Is chemically stable, can be heated in an autoclave (sterilized) and is inexpensive to manufacture.
- Is well tolerated and does not cause irritation or blurred vision after topical administration to the eye.
- Expands markets and generates new opportunities for existing drugs.
- Can extend drug product life cycles.