The synergy of nanoengineering coupled with biotechnology and pharmaceutical development has been well established over the past few decades particularly for biomedical applications. Nanocarriers were successfully developed to encapsulate different classes of therapeutics and have helped to tackle several challenges such as poor aqueous solubility, biodegradation, lower bioavailability, etc. To solve these issues, controlled delivery systems were rationally nano-engineered which facilitated sustained release of therapeutics ranging from days to even years. They have also enabled targeted delivery to specific locations of human body thereby localizing higher drug concentrations. This has played a vital role in improving patient compliance by reducing toxicity concerns and obviating the need for complex methods for repeated administrations. Biodegradable delivery systems have also evolved to a greater extent, and they eliminate the need for specialized procedures to remove non-biodegradable counterparts. Sustained release mechanisms via nano-engineered systems are well established and are generally attributed to diffusion, degradation, swelling, response to stimuli, etc. Some breakthrough innovations that have captured widespread attention over the past few years are those offering site-specific release of therapeutics with enhanced precision, improved targeting abilities and those driven by smart responses. Examples include natural resin-based particulate systems, biohybrid microrobots and stimuli-responsive nano carriers. The field is also witnessing a surge in rapid advancements with versatile nanocarriers encapsulating multiple therapeutic agents including imaging agents and targeting ligands for combination therapy and theranostic applications. Another aspect is the considerable progress in innovative delivery systems designed for nose to brain delivery of therapeutics via intra-nasal or trans-nasal routes, bypassing BBB and showing tremendous promise for neurodegenerative disease-therapies. Nano-engineered exosomes have recently manifested as a promising class of biologically derived vehicles for targeted delivery with reduced immunogenicity, substantial biocompatibility and the amenability to load therapeutics such as proteins, RNA and small molecules. Despite their enormous potential, significant challenges still exist for the clinical translation of nano-engineered ystems mainly owing to the hurdles associated with manufacturing scale-up, storage instabilities, potential adverse effects and complex regulatory pathways hindering bench to bedside translation.

The goal of this research topic is to bring together articles serving the objectives:

1) Collect more recent evidence of breakthrough innovations in nano-engineered systems for biomedical applications and how they establish novelty when compared to the existing or previous options
2) Understand more about the most recent challenges in this field and potential mitigations offering hope for clinical translation

We welcome the submission of manuscripts including, but certainly not limited to the following topics:
• Most recent innovations in nano-engineered systems and their promising potential relative to the existing modalities. These can include:

- Development strategies, in vitro, ex vivo characterizations, in vivo studies establishing efficacy and safety
- Innovations showing promising proof of concept but proved relevant compared to previous examples. This can include modern technologies such as use of AI in nanocarrier design, organ-on-chip testing platforms etc.
- Promising examples providing more insights into disease pathology, controlled delivery mechanism, combination therapy potential etc.

• Challenges hindering clinical translation of nano-engineered systems.

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Recent breakthroughs in nano-engineered drug delivery systems for biomedical applications