Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
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Volume 5 Number 1 2026
REVIEWS (Open Access)
Bridging the Translational Gap in Nanomedicine: From Biological Barriers to Regulatory Approval
Annachiara Bazzoni 1, Devyani Dogra 1, Chahat Antil 1, Natasha Phelps 1, Mustafa Rehmatulla Batliwala 1, Saina Depas 1, Gnanasekaran Ashok 2*
Biosensors and Nanotheranostics 5 (1) 1-8 https://doi.org/10.25163/biosensors.5110982
Submitted: 19 February 2026 Revised: 05 April 2026 Accepted: 15 April 2026 Published: 17 April 2026
Abstract
Nanomedicine has moved, slowly and unevenly, from laboratory curiosity to a recognised pillar of modern therapeutics. Liposomal doxorubicin, albumin-bound paclitaxel, the small interfering RNA therapy patisiran and, most visibly, the mRNA-lipid nanoparticle COVID-19 vaccines show what nanoscale carriers achieve when design, manufacturing and regulation align. These successes, however, sit beside a far larger body of candidates that never reach patients, and this review asks why. Peer-reviewed reviews, quantitative meta-analyses, survey and qualitative studies, and regulatory assessments published between 2012 and 2026 were synthesised and organised along the translational continuum running from bench discovery to market authorisation. Roughly 50 to 100 nanomedicines have been approved, dominated by lipid-based platforms and oncology indications, while more than 500 candidates remain in clinical testing. The barriers separating those two numbers are interconnected rather than isolated. In vivo, the protein corona rewrites a particle's synthetic identity, the mononuclear phagocyte system removes most of an injected dose, and the enhanced permeability and retention effect proves far more heterogeneous in patients than in rodents; a median of only 0.7% of administered nanoparticles reaches solid tumours. During scale-up, modest shifts in process parameters disturb critical quality attributes, which places Quality-by-Design, process analytical technology and microfluidic manufacture at the centre of pharmaceutical development. Clinically, success falls from about 94% in Phase I to 14% in Phase III, reflecting weak preclinical models, immunotoxicity and inadequate patient stratification, while fragmented regulatory definitions add further uncertainty. Structured frameworks such as DELIVER, combined with companion diagnostics, standardised reporting and early regulatory dialogue, offer the most credible route to narrowing this gap.
Keywords: nanomedicine; clinical translation; protein corona; enhanced permeability and retention effect; Quality-by-Design; nanotoxicology; regulatory science; DELIVER framework
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