Amphiphilic polymer-based enhancers for local drugs delivery to the inner ear

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https://research.brighton.ac.uk/en/projects/amphiphilic-polymer-based-enhancers-for-local-drugs-delivery-to-t

established November 2023

 

 

This project is supported by the Royal Society International Exchanges Scheme.

Hearing loss is one of the major health concerns worldwide. Currently, hearing cannot be restored once it is affected due to loss of cochlear sensory cells or due to degeneration of the stria vascularis, which is the source of the unique cochlear ionic and electrical environment. Hence, prevention of hearing loss is still the most viable way of approaching this problem. The efficiency of various drugs for prevention of hearing loss of different genesis has been shown by clinical research and practice in recent years. The inner ear, however, is one of the most challenging target organs for drug delivery. Conventional oral or parenteral routes of administration are largely ineffective because of the blood–perilymph barrier that maintains the microhomeostasis of the ear fluids and cells. Direct injection of drugs into the cochlea is also not feasible due to its poor accessibility and because of high risk of complications. Injections of drugs into the middle ear to allow for their diffusion through membranes of the round and oval windows, situated at the base of the cochlea, are considered to be the most practical route of drug delivery to the inner ear. Clinical research demonstrated that permeability of the round window for specific molecules depends on their physical and chemical properties. Consequently, application of specific drugs to the round window results in their large base-to-apex gradients in the cochlea. This can result in overdose of the drugs at the base and their insufficient concentrations at the apex. One of the solutions to this problem would be to locally enhance the permeability of the round window to specific drugs. We would like to develop and to test amphiphilic polymer-based enhancers for facilitating drug delivery through the round window and cellular membranes in the cochlea.

Project timeframe

 This project commenced in July 2016 and will end in July 2018.

Project aims

The major aim of this research proposal is to develop nano-micellar and in situ gel formulations for enhancement of drug delivery into the inner ear through the intact round window membrane of the cochlea and to test these formulations. Formulations will be based on amphiphilic polymers and corticosteroid drugs and their toxicity and efficiency for non-invasive drug delivery will be tested in cell cultures, tissue explants and in vivo experiments.

 DeliverytoInnerEar

 

Project findings and impact

£9,610, Royal Society International Exchanges Scheme

 Outcomes of the project not only provide an efficient formulation for delivery of corticosteroids into the inner ear but also will be used in development of advanced formulations for local delivery of peptides (apoptosis inhibitors, neurotrophic factors, antibodies) and plasmids for innovative therapy and gene therapy of the inner ear.

Research Team

Andrei Lukashkin (PI)

Irina Savina

John Smart

Victoria Lukashkina

 

Output

Kamalov M, Đặng T, Petrova N, Laikov A, Luong D, Akhmadishina R, Lukashkin AN, Abdullin T (2017). Self-assembled nanoformulation of methylprednisolone succinate with carboxylated block copolymer for local glucocorticoid therapy. Colloids and Surfaces B: Biointerfaces (revision submitted).

Partners

Kazan Federal University, Russia