Background

The scleral, cortical and blood-retinal barriers (BRB) in the eye and blood-brain barrier (BBB) in the central nervous system (CNS) prevent the entry of undesired/large substances. A big challenge in drug development for therapeutics in the eye/CNS is developing a delivery system that can cross these barriers and deliver the drug safely and effectively. There is also an increased demand for non-invasive delivery systems for new therapies developed to treat posterior segment disorders due to increased rates of ageing and diabetes. Treatments targeting vascular endothelial growth factor (VEGF) in binding conditions such as AMD and diabetic retinopathy (DR) currently require direct intraocular (intravitreal) injections which can be time consuming and costly.

The UDDS solves both of these problems with a novel combination of annexin with a liposomal mixture of Vitamin E derivatives, phosphocholine, phosphatidylserine and cholesterol that can carry different drugs (proteins, solids and chemicals) across the BBB, BRB and cornea/sclera. Since the components of the liposomal mixture with annexin is constitutive and physiological, there is no associated toxicity.

Technology Overview

UCL researchers have developed a novel drug-delivery system that has been shown to deliver large therapeutic antibodies to the posterior segment of the eye and even the brain ().

Figure 2: Universal Delivery

Figure 3: AnnexinA5

Figure 4: Topical delivery of Avastin

Stage of Development

Some work was done last year on the conjugate that allows for the crossing of the BBB in clinical trials. The Lucentis reference standard injection, produced at AMRI achieved 13 weeks stability with animals treated also showing no significant side effects except very. Mild local irritation. Clinical trials are scheduled to start after GMP manufacturing run in October 2020, with the expectation that the treatment will then be widely available and on the NHS within 5 years.

Benefits

98% of promising drug candidates cannot cross the BBB with large developmental cost implications. This means you end up with a lot of existing drugs that cannot be used in the CNS or eye because they cannot be transported across the BBB, BRB or cornea/sclera. The UDDS would allow these drugs to be utilised therapeutically for ocular, neurological and psychiatric brain diseases. E.g. AMD, diabetic eye disease, glaucoma, Alzheimer’s, Parkinson’s, Schizophrenia and Psychoses.

Applications

Is non-invasive and administered by eye-drops. This removes the need for repeated intra-ocular injections and skilled administration by injection, thus reducing costs.
Readily adaptable for delivery of hydrophobic and hydrophilic drugs e.g. corticosteroids and protein drug molecules.
Enables non-penetrant and larger drugs to cross the BRB to non-invasively enter the eye and BBB to non-invasively enter the CNS (and is patent protected).
Can deliver large biological molecules such as large monoclonal antibodies in addition to low Mr compounds.
BBB (CNS) penetration gives UDDS great applicability across a wide range of Neurological diseases including AMD, Alzheimer’s, etc.
Pharmacokinetics of the liposome and release profile of the drug cargo may be fine- tuned.
Reproducible uniformity of liposome size.
May be used for therapy or diagnosis of disease.
Can be coupled to non-invasive imaging to determine drug distribution.
Has the potential for intranasal or transdermal delivery but further testing is needed.

Opportunity

Available for licensing.

Universal Drug Delivery System (UDDS)

Patents

IP Status

Seeking