Nanoparticle-based drug delivery in the inner ear: current challenges, limitations and opportunities

Figures & data

Figure 1. A schematic representation of inner ear anatomy and intratympanic drug delivery.

Figure 2. A topographical representation of intracochlear drug delivery through cochleostomy.

Figure 3. Types of nanomaterials used for inner ear drug delivery.

Table 1. A summary of nanoparticles used for drug delivery into the inner ear.

Nanoparticle	Size range (nm)	FDA approved	Advantages/Limitations
Mesoporous silica	50–200 but can increase in size up to 150%	No	Biocompatible Straightforward functionalization Degradable High specific pore volume and surface area (drug loading > 30% weight) Unknown how well it transports across middle ear barriers
Hyperbranched polymer (poly l lysine)	3–10	No	Degree of branching and number of branches determines characteristic parameters
Micelle	30–120	Yes, oestradiol for menopause
Advanced liposome (lipoplex)	80–200	Yes, for various chemotherapeutics (i.e. daunorubicin, cytarabine, vincristine), antifungals, pain medicine	Most commonly used (liposomes were among the first nanocarriers) Commercially available Cationic (lipofectamine) can be used for gene delivery (binds – charged DNA) Can be PEG coated Simple, low toxicity
Lipid core	30–200	No	Hydrophobic triglyceride core and amphiphilic surfactant shell Carries both hydrophobic and hydrophilic molecules Easy to produce
Chitosan hydrogel	80–200	No	Polymer of randomly distributed d-glucosamine and N-acetyl-d-glucosamine Safe Biodegradable
Nanogel (hydrogel nanoparticles)	45–250	No	High water content Can be thermosensitive
Polyethylene glycol (PLLA-mPEG) and poly-lactide-co-glycolide (PLGA)	100–1000	Yes	Biodegradable polymers PLGA degradation controlled by lactic:glycolic acid ratio Carries both hydrophobic/hydrophilic molecules Even small variations in PLGA particle size leads to dramatic changes in nanoparticle efficacy of intracellular delivery Stable
Superparamagnetic iron oxide nanoparticles (SPION) composed of magnetite (Fe3O4) or maghemite (Fe2O3)	–	Yes, for imaging applications but many have since been withdrawn	Can be used for imaging Can be manipulated by external magnetic field and penetrate cells Can have either polymer or metal coating Magnetic field hyperthermia can trigger drug release Nontoxic, biocompatible, and biodegradable via Fe metabolism pathways Drawback is particle’s tendency to aggregate
Gold	<10	No	Can be used for imaging Plasmon resonance properties Versatile surface modifications Good biocompatibility Does not damage blood brain barrier integrity Widely used as drug carriers for various diseases
Polymersome	40–200	Various copolymer combinations approved, none for indications in the ear (prostate, multiple sclerosis)	Amphiphilic self-assembling block copolymers Assemble to vesicles in aqueous solutions Similar to lysosome structurally Stabilize drugs Afford controlled drug release
Cationic polymers (polyethylenimine (PEI), polyamidoamine)	–	–	Can be used for imaging
Magnetic iron oxide nanoparticles (MIONs)	100–300	Yes, for glioblastoma, iron deficiency anemia, and chronic kidney disease. Have been used in clinical trials in the ear	–
Poly (amino acid) (poly (2-hydroxyethyl l-aspartamide) (PHEA)-coated nanoparticles	20–150	No	Highly stable in water Biocompatible and biodegradable Simple polymer coating Easily functionalized to target specific moieties
Carbon quantum dots	–	No	Biocompatible and low toxicity Can cross blood brain barrier Not yet demonstrated in the cochlea