Feasibility Study: A Novel Technique for Forming Diffusion-Controlled Drug Delivery Polymer Microcapsules

Lead Research Organisation: University College London

Abstract

The development of microdevices for controlled drug delivery is currently an area of intense research activity. These devices enable localized administration of a given agent in vivo which maximises patient safety and comfort and can greatly reduce treatment costs. There are, however, two significant barriers in terms of cost and reliability which have hindered their uptake in clinical practice. Firstly, methods for efficient drug encapsulation which are both cost-effective and provide adequate quality control are lacking. In this proposal we identify a novel approach to drug encapsulation based on co-axial electro-hydrodynamic flow which offers a simple, one-step method for the mass production of polymer microcapsules. Secondly, a reliable means of controlling and/or varying the rate of drug release has yet to be developed. We will investigate the use of ultrasound to vary the rate of diffusion from implanted/injected devices to provide a means of controlling drug administration that is accurate and non-invasive. A successful outcome will have significant impact for the pharmaceutical and healthcare industries, from whom the project has already attracted considerable support, and will provide the basis for future, larger research projects to develop the work.

Publications

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Ahmad Z (2008) Generation of multilayered structures for biomedical applications using a novel tri-needle coaxial device and electrohydrodynamic flow. in Journal of the Royal Society, Interface

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Enayati M (2012) Modification of the release characteristics of estradiol encapsulated in PLGA particles via surface coating. in Therapeutic delivery

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Enayati M (2011) Electrohydrodynamic preparation of polymeric drug-carrier particles: mapping of the process. in International journal of pharmaceutics

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Farook U (2008) Novel co-axial electrohydrodynamic in-situ preparation of liquid-filled polymer-shell microspheres for biomedical applications. in Journal of microencapsulation

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Pancholi K (2009) In vitro method to characterize diffusion of dye from polymeric particles: a model for drug release. in Langmuir : the ACS journal of surfaces and colloids

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Pancholi K (2008) Dynamics of bubble formation in highly viscous liquids. in Langmuir : the ACS journal of surfaces and colloids

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Pancholi K (2008) Generation of microbubbles for diagnostic and therapeutic applications using a novel device. in Journal of drug targeting

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Pancholi K (2009) Novel electrohydrodynamic preparation of porous chitosan particles for drug delivery. in Journal of materials science. Materials in medicine

 
Description Polymer capsules from 400nm to 10 um in diameter were prepared using a co-axial electrohydrodynamic process. By controlling the main process variables (applied voltage and flow rate) and the viscosity of the polymer solution, the size and structure of the capsules prepared were contolled and a dye (simulating a drug) was successfully encapsulated in the polymer. The diffusion of the (blue) dye has been quantitatively assessed by colorimetry and on this basis a model has been developed to predict
Exploitation Route In the food and pharmaceutical industry; also in other sectors requiring encapsulation such as the cosmetics industry and materials engineering The technology has been patented (patent no. 1102148) and the investigators received a 2009 Royal Society Brian Mercer Innovation Award and the 2010 Worshipful Company of Armourers and Brasiers Venture prize to start a spin-out company (AtoCap) through which they are commercialising the technology. They have also commenced funded collaborations with Unil
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology
URL http://www.mecheng.ucl.ac.uk/research/biomedical-engineering/microencapsulation
 
Description The research funded by this grant has led to collaboration with a pharmaceutical company, Veloxis to explore the use of the fabrication techniques for drug encapsulation. It also seeded the research that led to the formation of our spinout company, AtoCap and associated patent application.
First Year Of Impact 2009
Sector Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic
 
Description Industrial studentship
Amount £32,000 (GBP)
Organisation Danish Agency for Science, Technology and Innovation 
Sector Public
Country Denmark
Start 01/2010 
End 01/2013
 
Description UCL Crucible award
Amount £5,000 (GBP)
Organisation University College London 
Department Crucible
Sector Academic/University
Country United Kingdom
Start 09/2011 
End 03/2012
 
Title LAYERED BODIES, COMPOSITIONS CONTAINING THEM AND PROCESSES FOR PRODUCING THEM 
Description A layered body comprising: a core region; at least one intermediate layer disposed around the core region; and an outer layer disposed around the at least one intermediate layer, wherein at least one of the at least one intermediate layers comprises a gas, the layered body having at least one dimension, measured across the body and through the core region, of 100 µm or less. 
IP Reference WO2012107760 
Protection Patent application published
Year Protection Granted 2012
Licensed Commercial In Confidence
Impact Formation of a spin-out company: AtoCap
 
Company Name AtoCap 
Description AtoCap was formed out of the research activity of the UCL Encapsulation Group run by company directors Prof. Mohan Edirisinghe and Dr. Eleanor Stride. Its core technology is based on a novel implementation of electrohydrodynamic (EHD) processing for the preparation of a wide range of encapsulated structures via a clean, efficient, one step route. 
Year Established 2011 
Impact Through close collaborations with clinicians at the Whittington Hospital, AtoCap has identified a first potential blockbuster application in the treatment of chronic urinary tract infections (UTI) - a debilitating condition that affects tens of millions of patients each year. Chronic UTIs are particularly prevalent amongst the elderly population, being identified as a major cause of incontinence, mental confusion and balance problems leading to falls and potentially fatal septicaemea and bladder cancer. Antibiotics are hampered by the difficulty of achieving sufficient localized urinary bactericidal concentrations, while high-dose systemic treatments are toxic and ill-tolerated. Thus, there is a great need for improved delivery systems to achieve the high concentrations of antibiotics needed to counter chronic infection in a localised manner. This will eliminate the significant drawbacks associated with the current oral and intravenous administration methods, specifically poor compliance with regular dosing regimens, poor uptake and side effects such as nausea, compromised immunity as well a build up of resistance over long treatment periods. There is currently no alternative to oral/intravenous administration of antibiotics and thus the potential market is substantial. Over the past year research has continued to optimize the generation of multilayered micro and nanocapsules for the encapsulation and controlled release of antibiotics. These results have provided key supporting data for the primary patent application and been published in leading academic journals. The research has been featured as the cover article in both the Journal of the Royal Society Interface and Macromolecular Rapid Communications.