Polymeric micelles, i.e. aggregation colloids formed in solution by self-assembling of amphiphilic polymers, represent an innovative tool to overcome several issues related to drug administration, from the low water-solubility to the poor drug permeability across biological barriers. With respect to other nanocarriers, polymeric micelles generally display smaller size, easier preparation and sterilization processes, and good solubilization properties, unfortunately associated with a lower stability in biological fluids and a more complicated characterization. Particularly challenging is the study of their interaction with the biological environment, essential to predict the real in vivo behavior after administration. In this review, after a general presentation on micelles features and properties, different characterization techniques are discussed, from the ones used for the determination of micelles basic characteristics (critical micellar concentration, size, surface charge, morphology) to the more complex approaches used to figure out micelles kinetic stability, drug release and behavior in the presence of biological substrates (fluids, cells and tissues). The techniques presented (such as dynamic light scattering, AFM, cryo-TEM, X-ray scattering, FRET, symmetrical flow field-flow fractionation (AF4) and density ultracentrifugation), each one with their own advantages and limitations, can be combined to achieve a deeper comprehension of polymeric micelles in vivo behavior. The set-up and validation of adequate methods for micelles description represent the essential starting point for their development and clinical success.

In the field of nasal drug delivery, nose-to-brain delivery is among the most fascinating applications, directly targeting the central nervous system, bypassing the blood brain barrier. Its benefits include dose lowering and direct brain distribution of potent drugs, ultimately reducing systemic side effects. Recently, nasal administration of insulin showed promising results in clinical trials for the treatment of Alzheimer’s disease. Nanomedicines could further contribute to making nose-to-brain delivery a reality. While not disregarding the need for devices enabling a formulation deposition in the nose’s upper part, surface modification of nanomedicines appears the key strategy to optimize drug delivery from the nasal cavity to the brain. In this review, nanomedicine delivery based on particle engineering exploiting surface electrostatic charges, mucoadhesive polymers, or chemical moieties targeting the nasal epithelium will be discussed and critically evaluated in relation to nose-to-brain delivery.

Introduction: Polymeric micelles represent nowadays an interesting formulative approach for ocular drug delivery, as they act as solubility enhancers of poorly soluble drugs and promote drug transport across cornea and sclera. In particular, in the last 5 years polymeric nanomicelles have been increasingly investigated to overcome some of the important challenges of the topical treatment of ocular diseases. Areas covered: The aim of this review was to gather up-to-date information on the different roles that polymeric micelles (commonly in the nano-size scale) can play in ocular delivery. Thus, after a general description of ocular barriers and micelles features, the attention is focused on those properties that are relevant for ophthalmic application. Finally, their efficacy in improving the ocular delivery of different classes of therapeutics (anti-inflammatory, immunosuppresant, anti-glaucoma, antifungal, antiviral drugs) are reported. Expert opinion: Although still a few, in vivo experiments have clearly demonstrated the capability of polymeric nanomicelles to overcome a variety of hurdles associated to ocular therapy, notably increasing drug bioavailability. However, there are still some very important issues to be solved, such as tolerability and stability; additionally, the role of micelles in drug uptake by the ocular tissues and their potential for the treatment of posterior eye diseases still need to be clarified/verified.