Big potential for small science
Every discussion about antimicrobial resistance (AMR) notes the slow, expensive and nearly empty development pipeline for new antimicrobial medicines.
But what if we could extend the efficacy of the drugs we already have?
That’s one of the benefits of nano-antimicrobial therapies, which have the potential ability to overcome mechanisms of resistance, target specific organisms or sites of infection, and reduce side effects.
However, there are many scientific and clinical challenges that stand in the way of implementation.
Dr Jen Payne is a researcher at CSIRO’s Manufacturing Research Unit and says that nano-antimicrobial therapies, when combined with current antimicrobials, could buy us time against AMR and improve patient outcomes.
“The scarcity of new antimicrobials means we need to get think of innovative ways to ensure our medicines continue to work.”
Nano vs AMR
Australia is experiencing a rising threat from AMR, where bacteria and other microorganisms can survive in the presence of drugs intended to eliminate them, such as antibiotics. This growing global problem is accelerated by the inappropriate use (overuse, underuse, and misuse) of antimicrobials in humans and animals.
AMR undermines the effectiveness of medicines and makes infections more difficult to treat.
The development of nano-antimicrobials offers a promising solution to combat AMR as it enables a range of mechanisms that conventional antimicrobials lack, including the ability to deliver drugs to a specific target within the body, to disrupt drug-resistant biofilms, or limit microbial development itself.
Professor Branwen Morgan, CSIRO’s Minimising AMR Consortium Lead, says that existing drugs that are used to treat non-infectious diseases also have a role in combatting AMR.
“Many medicines have effects in the body beyond their primary target. Drug repurposing exploits these additional functions, which may include antibacterial activity,” says Professor Morgan.
“Having nano-formulations of repurposed drugs could give us an even larger set of treatment options in a shorter space of time.”
But there are several challenges that need to be addressed.
“While nano-antimicrobials are a potential niche opportunity, they will encounter the same market access and commercialisation issues faced by other AMR solutions,” says Dr Payne.
“To fully understand their value, we need more clinical trials, coupled with innovative pricing and reimbursement mechanisms to encourage investment.”
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“The scarcity of new antimicrobials means we need to get think of innovative ways to ensure our medicines continue to work.”
Dr Jen Payne
What are nano-antimicrobial therapies?
Nano-antimicrobial therapies are part of a growing area of medicine known as nanomedicine, which that uses tiny particles, called nanoparticles, to prevent, find, treat, and monitor diseases.
Because it uses new technology at the super-small scale of nanometres (one nanometre is equal to one billionth of a metre), nanomedicine offers the potential to treat currently difficult or untreatable diseases.
Nanomedicine can be instrumental in the development of precision medicine, which is a future vision where treatments are completely personalised. This involves delivering the precise amount of medication at the optimal time, targeting the exact location in the body, thereby maximising effectiveness and minimising harm to healthy tissues.
Understanding the challenges of nano-antimicrobials
Australia’s clinical trial landscape offers advantages such as expedited clinical trials and R&D tax incentives. However, antimicrobial trials face challenges, including low infection rates, difficulties recruiting patients in remote areas, and limited inclusion of Indigenous communities.
Transitioning from R&D to clinical trials
Public awareness and trust are crucial for trial support, while the lack of rapid diagnostics hinders pathogen identification and patient recruitment, further complicating antimicrobial research efforts.
Commercial viability in the face of rapid AMR and changes with push and pull incentives
The current NAM pipeline
The paper reviewed global nano-antimicrobial based-clinical trials over the last six years, and analysed the data to identify trends and challenges in the development of nano-antimicrobial therapies.
Dr Payne says the number of nano-antimicrobial-based clinical trials has increased significantly in the last decade, with 46 trials conducted or planned globally, with two here in Australia.
“Many of these trials are still in early stages, or with small participant numbers,” Dr Payne said. “This makes it difficult to show the significance of nano-antimicrobials’ potential benefits.”
Evidence requirements and Australian regulatory needs
Unlike well-defined small molecule or protein therapeutics, which have defined values for their formulation composition (such as purity, size, solubility and other metrics). Nano formulations, however, have a distribution of particles, which means they display a range of values for their various properties.
“This naturally has ramifications both biologically and in terms of the manufacturing process,” says Dr Payne.
“We need to consistently characterise nano-formulations and improve TGA guidelines so that the regulatory framework can accommodate the unique properties .”
While the potential for nano-antimicrobials is positive, the pathway to impact still has many hurdles. Dr Payne says this is the nature of any innovation, and the paper is intended as a call-to-action for government and industry to work together.
“Understanding these challenges may help accelerate progress so we can start to see real results,” says Dr Payne.
For further insights, read An Australian perspective on clinical, economic and regulatory considerations in emerging nanoparticle therapies for infections, a review published in npj Antimicrobials and Resistance. The review is a collaboration between researchers from CSIRO, University of Newcastle, Monash University and RMIT.
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