HEMS 2: Development of novel nano-encapsulated drug to overcome cancer stem cells and target glioblastoma

Faculty: Health, Education, Medicine and Social Sciences

Supervisors: Prof Mohammad Najlah; Dr Havovi Chichger; Dr Ibrahim Tolaymat

Location: Chelmsford

The interview for this project is expected to take place on Tuesday 18 April.

Glioblastoma multiforme (GBM) is one of the most lethal and aggressive forms of malignant brain tumours in adults.

Despite multimodal treatment, including surgical resection with concurrent and adjuvant radiotherapy and chemotherapy, the prognosis of GBM is poor with a median survival time of only 14.6 months and less than 5% of GBM patients surviving for more than two years.

Glioblastoma-resistant stem cells (GSC) are the major cause of glioblastoma multiforme (GBM) chemotherapy failure. Conventional chemotherapy, including the most advanced practice of intracerebral chemotherapy of glioblastoma, has had very limited success due to poor brain penetration of drugs.

The impermeable nature of the blood-brain barrier (BBB) and/or low targeting efficacy of systemically-administered drugs limit their therapeutic efficacy against glioblastoma.

Additionally, there are several issues associated with chemotherapy such as poor bioavailability, rapid degradation, and toxic side effects. Therefore, alternate approaches are needed to address this therapeutic issue for patients with GBM.

Intranasal (IN) drug administration offers a direct pathway for the transport of drugs traversing along olfactory or trigeminal nerves, bypassing the BBB into the brain.

Furthermore, drugs applied IN may traverse the epithelium at the upper olfactory regions to gain access into the cerebral spinal fluid.

Therefore, nose-to-brain delivery of anticancer drugs has gained significant interest recently owing to its great potential to resolve issues associated with drug administration such as BBB permeability, low stability or/and intense first-pass metabolism.

Recently, we have synthesised a series of novel anticancer compounds (ACA0522) derived from safe nutraceutical compounds. The main breakthrough with ACA0522 is that the compound is safe, water-soluble, non-toxic, with potent anti-cancer activities.

ACA0522 has reverse pan-chemoresistance activity (i.e., stronger than some established toxic drugs) and the compounds are feasible to synthesise and produce at a large scale as compared to licensed anti-cancer drugs.

Our preliminary studies show that using nanocarriers, such as liposomes, to encapsulate ACA0522 results in a significant increase in the anticancer activity of the compounds observed in vitro.

This might be due to the increased cellular uptake of such lipid vesicles (the liposomes). Our data demonstrates the significant potential for this discovery to impact cancer therapeutics.

In this PhD studentship project, we aim to use these findings to further the development of ACA0522 as a promising anti-cancer therapeutic. We propose that encapsulating our novel anticancer compounds, ACA0522, within a lipid nanocarrier suitable for nose-to-brain direct inhalation will allow localised and targeted treatment of glioblastoma.

The “short-cut” between the nasal cavity and the brain makes the nose-to-brain venue a promising non-invasive route which bypasses the blood brain barrier (BBB) and improves the bioavailability of the drug in the brain.

Key objectives:

  1. To design, formulate, characterise, and biologically evaluate anticancer delivery systems of ACA0522 alone and in combination with anticancer drugs (such as paclitaxel)
  2. To study the potential of nose-to-brain delivery to treat glioblastoma.

This cross-faculty, laboratory-based PhD will be performed in our SuperLab facilities and the Pharmaceutical Research Laboratory. Our facilities are equipped with a wide range of state-of-art facilities to produce, characterise, and biologically evaluate nanomedicines for therapeutical applications, especially, anti-cancer-treatments.

With a background in pharmacy, pharmaceutical science or a relevant field, you will be able to fulfil a vital role as a multidisciplinary team member helping to further develop a cancer treatment.

The ARU Pharmaceutical Research Group has outstanding research with a range of successful bids, KTP, KEEP+ and research contracts, PhD completions, peer-reviewed research outputs and wide network of national and international collaborations.

This project is in collaboration with GMPriority Pharma Ltd, experts in liposomes. In addition to matched funding, GMPriority Pharma Ltd will offer their research and development laboratories and facilities whenever needed during the project.

If you would like to discuss this research project, please contact Prof Mohammad Najlah: mohammad.najlah@aru.ac.uk

Apply online by 19 March 2023

Funding notes

This successful applicant for this project will receive a Vice Chancellor’s PhD Scholarship which covers Home tuition fees and provides a UKRI equivalent minimum annual stipend for three years. For 2022/3 this was £17,688 per year. The award is subject to the successful candidate meeting the scholarship terms and conditions. Please note that the University asserts the right to claim any intellectual property generated by research it funds.

Download the full terms and conditions.