Abstract
Background
Injectable nanomedicines undergo several preparation and administration steps between the original container and the patient, including dilution, transfer to syringes or infusion bags, storage, agitation, and device passage. These steps may affect important quality attributes of nanomedicine formulations. However, in-use stability is often evaluated using conventional physical measurements such as particle size, which may not always reflect changes in drug encapsulation, cargo integrity, or functional performance. Evidence on how specific in-use conditions affect nanomedicine quality remains fragmented across different formulations and stages of administration.
Objective
To map the available experimental evidence on in-use quality risks in injectable nanomedicines and identify the handling conditions and quality attributes associated with changes during preparation, storage, and administration.
Method
A scoping review and evidence-mapping approach was used to identify peer-reviewed, full-text experimental studies evaluating injectable nanomedicines under preparation-, handling-, or administration-related conditions. Eligible studies assessed at least one measurable physicochemical quality attribute or functional outcome following an in-use intervention. Evidence was mapped according to nanomedicine platform, stage of the in-use pathway, handling condition, analytical method, quality attribute assessed, and direction of observed change.
Results
Eleven studies covering lipid nanoparticles, liposomal formulations, and albumin-based nanomedicines were included. The studies investigated dilution or reconstitution, post-preparation storage, temperature exposure, agitation and mechanical stress, syringe or needle passage, and administration-device exposure. Mechanical stress showed formulation-dependent effects. Vigorous shaking or vortexing affected several mRNA–lipid nanoparticle systems and was associated with increased particle heterogeneity, cargo release, or reduced mRNA integrity, while routine aspiration or syringe storage was generally better tolerated under the conditions tested. In drug-loaded nanomedicines, dilution medium, concentration, and prolonged post-preparation storage influenced colloidal stability, aggregation, drug retention, or redispersibility. In some studies, changes in payload retention or functional integrity occurred without substantial changes in particle size. Evidence covering the complete preparation-to-administration pathway was limited and heterogeneous across nanomedicine platforms.
Conclusion
Available evidence suggests that in-use quality risks in injectable nanomedicines depend on both the formulation and the type of handling stress. Importantly, preserved particle size did not always indicate preservation of payload or functional integrity. Therefore, particle size alone may not be sufficient to assess in-use stability. Product-specific evaluation using complementary physicochemical and functional attributes may provide a more complete assessment of nanomedicine quality during clinically relevant preparation, handling, and administration. Further standardized studies are needed, particularly for less investigated stages of the in-use pathway.
| Has the manuscript been published | not published |
|---|---|
| Intend to be published in the IJPS ? | Yes |
