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Stack #4636322
| Question | Answer |
|---|---|
| List the structure of the ear | - External ear - Middle ear - Inner ear - TM |
| Describe the external ear | From pinna to tympanic membrane TM |
| Describe Middle ear | Usually air-filled cavity with temporal bone of skull around it. |
| What connects to the inner ear + nasopharynx? | Eustachian tube |
| What is part of the inner ear? | 1) COCHLEA (auditory organ) 2) VESTIBULAR SYSTEM (organ of balance) |
| The TM varies in whiteness how thick? | 80-100 microm |
| What is the TM? | Tympanic membrane |
| What is the OW? | Oval window |
| What is the RW? | Round window |
| What is otic drug delivery used to treat? | both MIDDLE + INNER ear disorders |
| What can otic drug delivery treat? | - infectious conditions e.g. acute + chronic otitis media - inflammatory conditions - Balance disorders - Hearing disorders |
| Name one balance disroder | Meniere’s disease |
| Nae some hearing disroders | Sensorineural hearing loss, tinnitus |
| What are the different types of drugs used in otic drug delivery? | - antibiotics - antifungals - steroids - local anaesthetics |
| Middle ear infections are usually treated with what drug administration?q | Systemic drug administration |
| Why is the INNER EAR difficult to treat systemically? | Due to limited drug delivery (barriers between blood + fluid-filled spaced) —> think of topical therapy |
| What is the eardrum? (TM tympanic membrane) | —> thin connective tissue with skin on the outside + mucosa on the inside, separates the outer ear from the middle ear |
| What are the different layers of the TM? | 1) outer layer 2) Middle Ayer 3) Inner layer |
| Describe the outer layer of TM | Stratified squamous keratinised epithelium (like skin) |
| Describe the Middle layer of TM | Collagen-rich layer |
| Describe the inner layer of TM | Cuboidal mucosal epithelium |
| The TM is impenetrable to most things except what? | Small, mainly lipophilic molecules |
| Perforation causes what to happen? | Middle ear infection , possibly hearing loss |
| Acute (wet) perforations often heal within how many weeks? | Within weeks |
| What do chronic cases of perforations require? | Surgery e.g. myringoplasty/ tympanoplasty |
| What are some modern approached for TM repair? | 3D printed grafts |
| What is current standard for TM perforations? | Autologous graft (patch) inserted behind the ear |
| What is a PhonoGraft? | Minimally invasive, canal-inserted biomaterial that supports self-healing |
| What is Cerumen? | Ear wax |
| What is Cerumen / ear wax composed of? | - sebum - shed skin cells - sweat - debris |
| What is the function of Cerumen? | —> provides a protective coating + traps particulates, helping move them away from the tympanic membrane TM via hair + epithelial migration int he auditory canal |
| Ear was is acidic why? | Inhibits bacterial growth |
| Impaction/ blockage by ear wax is due to what? | Narrow auditory canal - excessive Cerumen production - use of cotton-tipped applicators |
| List some symptoms of blockage | - tinnitus - vertigo - ear pain - feeling fullness |
| Other foreign bodies like live insets or small objects may cause what in the ear? | Inflammation such as otitis external |
| What are some treatment options of Cerumen? | Cerumenolytic ear drops to soften/ loosen wax e.g. OTEX |
| what are the 3 auditory ossicles? | 1) Malleus 2) Incus 3) Stapes |
| Describe the 3 auditory ossicles? | —> Among the smallest bones in the body - transmit + amplify sound vibrations from the TM - transfer sound from air to the fluid-filled inner ear |
| What is the purpose of the EUSTACHIAN tube? | - connects middle ear to nasopharnx - can clear drugs administered into the middle ear |
| What is the round window RW membrane (70 microm thick)? | Common route for inner ear drug deliver - accessed after injection through the TM |
| What is the organ of hearing? | COCHLEA |
| what is the organ of balance? | VESTIBULAR SYSTEM |
| What are the purpose of hair cells? | —> sensory receptors for detecting sounds + motion |
| Where are hair ells located? | In the spiral cochlea within the ORGAN OF CORTI |
| What does the organ of corti do? | Sensory receptor converts sound vibrations into nerve impulses for hearing |
| Hair cells contain what? | Mechanorecpetors with cilia of varying heights to detect sound frequencies |
| What is the mechanism of inner ear / hair cells? | Movement of cilia generated nerve impulses + signals transmitted to th brain |
| What are some common indications for paediatric otic drug formulations? | - otitis external - otitis media - Cerumen removal |
| List some dose considerations for paediatric otic drug formulations | Small volumes must be used |
| List some paediatric considerations | - outer ear not fully developed at birth - external auditory canal is straighter + narrower in infants - ear physiology changes with age |
| Describe NON-INVASIVE drug delivery across TM: | —> diffusion to middle ear through TM (stratum corneum restricts permeability) |
| Describe INVASIVE drug delivery across TM | —> injection/ device crossing TM Or drug delivery system on RW allowing diffusion of drugs to inner era (or other processes such as endocytosis) No stratum corneum in RW compared to TM |
| Topical otic drug delivery, formulations often resemble what? | Transdermal drug systems + designed for diffusion across TM or RW membranes |
| Where does topical application occur? | On EXTERNAL AUDITORY CANAL |
| List some common formulation of topical otic drug delivery | - antibiotics - antifungal (gels + foams) - with or without cotton wool plug |
| Why are topical otic drug deliveries good? | - can achieve HIGHER local conc. than systemic therapy - Allow combination drug treatments - Rapid action + generally good patient compliance particularly for paediatric patients |
| What is one rick for topical otic drug delivery at HIGH concentrations? | Risk of OTOTOXICITY!!! |
| List different Non-invasive delivery systems | 1) Hydrogels (reverse thermal gelling) 2) Chemical permeation enhancers (CPEs) 3) Combination strategy 4) Nanocarriers + physical means + combination = research stage) |
| What is one key point for hydrogels? | Drug MUST remain in contact with TM for sufficient time (difficult with children) |
| Describe Hydrogels | - gels = liquid at room temperature—> gel at body temperature - easy administration then forms a semi-solid depot in situ |
| List some adv of hydrogels | - prolonged residence time on TM - sustained drug release - reduced dosing frequency |
| List some formulation consideraitons for hydrogels | - mechanical properties (appropriate stiffness + controlled degradation ate) - must NOT impair hearing or cause discomfort - Biocompatibility + safety are essential |
| Give an example of a hydrogel | Poloxamer 407 |
| Describe CPEs | - increase drug flux across biological barriers by altering lipid structure or membrane permeability (hydrogels can NOT) - based on same principles as transdermal delivery |
| Give examples of CPEs | Surfactants e.g. limonene, sodium dodecyl sulfate |
| What can CPEs be combined with and why? | With hydrogels to achieve prolonged contact time + enhanced barrier penetration but MUST balance enhanced delivery/ permeability with safety + ototoxicity risk |
| Give some examples of Nanocarriers + physical means | - polymeric nanoparticles - liposomes |
| Describe Nanocarriers + physical means | - diameter <1 microm improved ability to cross biological backers TM, RW -protect drug from degradation + improve solubility - enable controlled or sustained release e.g. PLGA nanoparticles |
| A nw research suggests combination strategy explain | PERMEATION ENHANCERS e.g. surfactants + lipid modifiers being investigated to improve drug flux across barriers. |
| What are some different INVASIVE delivery systems? | 1) Hydrogels (invasive) 2) Nanoparticles + magnetic nanoparticles (minimally invasive approach) 3) Ultrasound-mediated inner ear drug delivery 4) pump/ catheter (intra-cochlear) |
| how are invasive hydrogels delivered? | Via intratypanic injection forming a DRUG DEPOT int he middle ear. |
| how do hydrogels invasive work? | Reduces clearance through the Eustachian tube +prolongs contact with the round window membrane |
| Give examples to invasive hydrogels | 1) OTIPRIO —> thermosensitive gel, liquid at room temp. Sustained antibiotic release. 2) HYALURONIC ACID —> flows during injection investivative approach for inner ear therapy |
| How are nanoparticles + Magnetic nanoparticles delivered? | Via INTRATYMPANIC injection for targeted inner ear therapy |
| What do nanoparticles + magnetic nanoparticles do? | Enhance localisation + retention at RW membrane - surface modification improves tissue penetration |
| List some surface modifications | - PEGylation - Ligand conjugation |
| For nanoparticles + magnetic… what do pH responsive systems enable? | Drug release in mildly acidic inflammatory environments (investigational) - magnetic nanoparticles can be guided using an external magnetic field s |
| Describe ultrasound mediated inner er drug delivery (experimental) | - minimally invasive technique use with INTRATYMPANIC administration - ultrasound induces MICROBUBBLE CAVITATION at RW membrane - temporarily increases membrane permeability enhancing drug diffusion into inner ear |
| Describe pump/ catheter delivery system | - mainly tested in animal models to control low diffusion rates - programmable + implantable delivery devices - used to precise control of drug release |
| What is the SILVERSTEIN MICROWICK | Wick inserted though tM to access round window - drop administered in outer ear diffuse through wick |
| What are some challenges of ear delver? | - patients still prefer oral drug admin - ease application - cost - pain - variability on drug conc. across TM? - a lot of studies on animal not human trials yet! |
Created by:
Study109