Challenges and feasibility of the scaled-up production of nanomedicines

by Hii Yiik Siang and Dr Stephanie Chan

The continuous development of the medical industry has led to the development of nanomedicine, which is being touted as the future of medicines. Nanomedicine is an emerging scientific specialty born from nanotechnology and incorporated into medicine.

Nanomedicine involves monitoring, repairing and controlling the human biological system at molecular level. It also offers unique opportunities for developing new therapeutic approaches to diagnosing, preventing and treating life-threatening diseases.

There are two main branches of nanomedicine, namely organic nanoparticles and inorganic nanoparticles. Organic nanoparticles are derived from natural or synthetic organic molecules through self or chemical binding such as liposome, dendrimers, polymeric micells and others. Inorganic nanoparticles are synthesised from inorganic groups such as quantum dots, metal nanoparticles and others.

The United States Food and Drug Administration (FDA) and the European Medicines Agency (EMA) are the regulatory bodies that monitor the quality of nanomedicines. It is understood that the biological properties and the biodistribution patterns of nanomaterials can be easily altered through minor modification in the manufacturing processes.

When the biological properties are altered, performance factors such as drug release, metabolism assessment, protein binding and specific cellular uptake capability will be affected.

During the manufacturing process, it is not only the production of nanomedicine that will be up-scaled, but also the toxicity of the drugs. Therefore, the FDA has suggested performing toxicity screening in terms of the drugs’ physiochemical characteristics through both in vivo and in vitro models.

Nanomedicine has the benefits of personalising medicine to treat numerous diseases. However, there are four challenges faced by the nanomedicine manufacturing industry. They are biological understanding, safety concerns, regulatory concerns and manufacturing related issues.

Current delivery systems suffer from major hindrances such as rapid clearance by the immune system, low targeting efficiency and difficulty in crossing biological barriers. Hence, a better understanding of how delivery mechanisms affect intracellular uptake, trafficking and the fate of nanomaterials in a complex biological network is needed in pre-clinical and clinical trials before the manufacturing process.

In terms of safety, it has been reported that nanomaterials may contribute to the formation of free radicals, damage of brain cells and undesirable penetration through the epidermis or other physiological barriers into areas of the body that are more susceptible to toxic effects.

Thus, establishment of standards and testing protocols to benchmark the development of nanomedicines are essential before products can be safely administered to patients.

Another challenge faced during clinical translation is lack of knowledge in high-throughput in vitro screening platforms that can evaluate the efficacy and toxicity of nanomedicine. As the development of nanomedicine is a fast-paced innovation, it can lead to inadequate standards and protocols for safe clinical use and production scale-up, thus creating barriers in regards to public acceptance, investor’s interest and commercial approval.

Lastly, a balance must be achieved in terms of the scalability of nanomedicines with demand, product functionality and physiochemical properties.

Society at large has abided to the prescribed administration of nanomedicine in disease treatments, and at the same time, nanopollution mitigation plans have to be enforced in the manufacturing processes. Hazardous, toxic or even chemically reactive nanomaterials should be handled carefully and legislation is required to regulate the sale of nanomedicines to patients.

The relevant EU legislation on risk management is Article 8 (3) (ia) of Directive 2001/83/EC, which states that ‘the marketing authorisation application shall be accompanied by a detailed description of the pharmacovigilance, and where appropriate, of the risk management system which the applicant will be introduced’.

In conclusion, the assessment of existing nanomedicine has provided a new platform for the examining specific aspects of nanomedicines. Scientific challenges have arisen from the limitations of high-throughput toxicity screening and the underlying reliability of nanomedicines in targeted treatment.

Undoubtedly, in pre-clinical trials, many developed nanomedicines have shown positive effects in their delivery, but many issues are yet to be addressed for up-scale manufacturing.

Hii Yiik Siang is a recent chemical engineering graduate and Dr Stephanie Chan a senior lecturer of petroleum engineering in Curtin Sarawak’s Faculty of Engineering and Science. Hii was supervised by Dr Chan in her final year research project entitled ‘Green synthesis of MgO nanoparticles using leaf extracts of Calotropis gigantean: Optimisation, Formulation and Kinetic Study’. Dr Chan specialises on bionanotechnology for the development of nanoparticles in various disciplines such as pharmaceuticals, biofuels, agriculture and bio-products. Dr Chan can be contacted by e-mail to chanyensan@curtin.edu.my.