The Delivery of Drugs and Genes  (D2G2) Group, led by Professor Mark Kendall, focuses on fundamental research and applied techniques for needle-free vaccination delivery systems.  One of our foremost developments is the Nanopatic developed at the Australian Institute for Bioengineering and Nanotechnology (AIBN).

Research Programs and Case Studies

D2G2 Research Focus

AIBNs Delivery of Drugs and Genes Group (D2G2) lead by Professor Mark Kendall focuses on physical methods for delivering biomolecules and stimuli to key immune response-inducing cells located in the skin; and extracting important biomolecules for diagnostics purposes.

The ultimate goal of the research is to dramatically improve the cost and efficiency of vaccination and treatment of major diseases, such as malaria and influenza. To achieve this goal, the group is:

developing needle-free gene and drug delivery and extraction technologies to and from the skin

investigating micro-nanoprojection array patch (Nanopatch) technology                                    

measuring the key biological and mechanical properties of skin

assessing clinical application

This multidisciplinary research spans biomedical engineering (fluid mechanics; micro-nanofabrication; solid mechanics), diagnostic (multi-photon microscopy) and dermatology and vaccinology.

The D2G2 group has research projects covering:

micro-nanoprojection patches for minimally-invasive and targeted delivery of genes and drugs to skin cells micro-nanoprojection patches for targeted gene and drug delivery to the skin and improved DNA vaccines
micro-nanoprojection patches for improved sampling in diagnosis of disease multi-photon microscopy for in vivo imaging following delivery of drugs and vaccines to skin
MPM non-invasive imaging of biological interactions following drug delivery with micro-nanoprojection patches

measurement of mechanical properties in skin at the cellular and subcellular scale

developing medical devices for clinical use  
Research Program: Cell death as immune enhancer in vaccine delivery

Vaccines are predominantly administered intramuscularly or subcutaneously. In order to mount a protective immune response, frequently immunostimulatory components (ie adjuvants) are co-administered. Separately, developing new vaccines and adjuvants is a costly and time consuming process, with unknown outcome. Here, we propose to use a skin immunisation device (the Nanopatch) to evoke localised skin cell damage that serves as a physical immune enhancer similar to an adjuvant. Current results strongly support the hypothesis of physical adjuvantation and provide new approaches for vaccination approaches – and routes. This project explores the underlying mechanism of physical adjuvantation using various immunological assays and imaging approaches.

 

Lead investigator Dr Sandra Depelsenaire
Research Group: Kendall Group
Contact Email: a.depelsenaire@uq.edu.au

 

Case Study: Gene and Drug Delivery and Diagnostics Through the Skin

Group Leader Professor Mark Kendall is inventor of the patented Nanopatch technology, which has a number of benefits over the more than 160-year-old hypodermic needle that is synonymous with the medical field.

“The Nanopatch could level the global playing field in health, providing safe vaccinations to the developing world, potentially overcoming many of the challenges of the traditional needle,” Professor Kendall said.

The Nanopatch is designed to target the immune-rich cells of the skin’s outer layers (the epidermis and upper dermis) with an array of thousands of micro projections – invisible to the naked dye – on a single patch.

Vaccines are dry-coated onto the patch, helping to eliminate the need for the vaccine cold chain which is both expensive to maintain, and risks being broken in underdeveloped regions that have poor access to electricity networks.

“In animal studies, we have shown the Nanopatch generates equivalent and protective immune responses as the needle and syringe (into muscle) but only needs to deliver a small fraction of the dose (eg 1/100th). Steps are underway to translate this to humans,” Professor Kendall said.

The UQ start-up company Vaxxas would founded in 2011 with the aim of taking the Nanopatch through clinical testing and along the commercial pathway to a product in market.

Development of the Nanopatch continues, with plans for a safety trial using blank (no vaccine applied) Nanopatches to take place locally in Brisbane, followed by a field trial in Papua New Guinea.  The technology has also been licenced to Merck and Co for the development of further vaccines to work in conjunction with the Nanopatch.

Highlights

Working with the World Health Organisation, US Centre for Disease Control and Prevention and Vaxxas, Professor Kendall’s team has been testing the utility of polio vaccines with Nanopatch.  They have shown that in rats, using just a fraction of the does that is required with a needle and syringe, the Nanopatch generates functional immune responses (Scientific Reports).

During the year the group published work in Vaccine highlighting the first use of a pneumococcal-conjugate vaccine delivered using micro projections, showing that delivery to the skin’s stratum corneum resulted in an immunogenic response. Pneumonia is a leading cause of death in children globally under the age of five, and was estimated to cause more than 900,000 childhood deaths in 2015.

Another advance included the development of micro projection technology which selectively extracts biomarkers from the skin – with minimal invasion – for the detection of disease. Work published in Biointerphases demonstrated in vivo application of the system with successful detection of the dengue NS1 disease biomarker (see Case Study 2: Nanopatch scales up in blood test quest).

Other developments underway within the group include nano 3D printing and further improvement of point-of-care biosensor techniques to analyse body fluid samples.

“Our work brings with it challenges of working in the materials science space and directly applying it with biological systems” he said.

In 2015 Vaxxas attracted a further $25 million in Series B venture financing to enable the development of further clinical platforms and vaccines for diseases which could be suitable for the dry-coated application. 

 

Case Study: Nanopatch Scales up in Blood Test Quest

The Kendall group is developing a device, which rather than delivering vaccine to the skin, instead takes biological samples away as a needle-free blood test.

Professor Mark Kendall said the Micropatch features projections designed for selectively-extracting biomarkers from the outer layers of the skin, rather than needing a needle or lancet for a blood sample.

“By applying the Micropatch to the skin, and leaving it on for under an hours, the micro projections are exposed to the fluid in the skin – which includes blood in the capillaries – capturing protein biomarkers which can be analysed when the patch is removed,” Professor Kendall said.

“The device is being advanced to have ‘plug-and-play’ functionality with a diagnostic reader. Achieving this will allow for quick and easy diagnosis of diseases such as dengue fever or malaria.”

Professor Kendall said that while blood samples taken with a needle and syringe are effective, the Micropatch offers a number of competitive advantages.

“The obvious advantage is that the Micropatch is far less invasive than a needle.  But potentially of even greater relevance, we envisage that as a diagnostic tool the Micropatch would offer an immediate diagnoses,” he said.

“Currently patients have to wait for a diagnosis, especially in developing countries; whereas an immediate diagnosis allows treatment to begin straight away.”

Kendall Group PhD student Kye Robinson was the first author on a paper published in Biointerphases, and said the Micropatch has a number of differences from the Nanopatch.

“The Micropatch is designed with different projection shapes to sample material, with surface chemistry to allow for the selective extraction of biomarkers,” Mr Robinson said.

The projections featured on the Micropatch are also longer than those on the Nanopatch, due to the need to access deeper into the skin. Despite this, the Micropatch only delves as far as the capillary loops in the dermal papillae – or fingerprint – for target probes to capture target biomarkers.

Proof of concept was successfully established during the study, with in vivo captures of antibodies specific to the dengue NS1 protein from the skin of a live mouse model.

In 2011, Professor Kendall founded the UQ start-up Vaxxas, which achieved initial capital raising of $15 million to advance the Nanopatch through clinical testing and along the pathway to a commercial product.  A further $25 million was secured during the year through Series B venture financing, which will fund clinical programs and the application of further vaccines which can be used on the platform.