drug delivery systems michael g. stewart, md, mph professor and chairman department of...
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Drug delivery systems
Michael G. Stewart, MD, MPHMichael G. Stewart, MD, MPHProfessor and ChairmanProfessor and Chairman
Department of OtorhinolaryngologyDepartment of Otorhinolaryngology
Paranasal sinuses & middle ear
• Frequent sites of infection, inflammationFrequent sites of infection, inflammation• Lined by mucous membrane (mucosa) with Lined by mucous membrane (mucosa) with
good capacity for absorptiongood capacity for absorption• Current surgical managementCurrent surgical management
• Opening, ventilation, irrigationOpening, ventilation, irrigation
• Potential problems & issuesPotential problems & issues• Access to cavityAccess to cavity• Maintenance of medication doseMaintenance of medication dose
Other potential locations
• Into abdominal cavityInto abdominal cavity• Into chest cavityInto chest cavity• Intra-vascularIntra-vascular• Directly into tissue, joint, muscleDirectly into tissue, joint, muscle
Sinus: clinical diseases
• Chronic inflammatory sinus diseaseChronic inflammatory sinus disease• Chronic infectionChronic infection• Nasal polypsNasal polyps• Fungal sinusitisFungal sinusitis• Cystic fibrosisCystic fibrosis• Other diseases of mucus and cilia transportOther diseases of mucus and cilia transport
Paranasal sinus anatomy
Normal sinus CT
Normal middle turbinate, left side
Nasal polyps
Large nasal polyp
Endoscopic sinus surgery
Endoscopic sinus surgery
Endoscopic sinus surgery video
Problems – sinus disease
• Access to sinus cavitiesAccess to sinus cavities• Mucosa is source of inflammation, polyp Mucosa is source of inflammation, polyp
regrowthregrowth• Inhaled solutions go directly to back of noseInhaled solutions go directly to back of nose• Irrigated solutions go partially into some Irrigated solutions go partially into some
sinusessinuses• Oral or intravenous meds go to mucosaOral or intravenous meds go to mucosa
• Problems with long-term use of steroids Problems with long-term use of steroids and antibiotics, antifungal meds and antibiotics, antifungal meds
Problems – sinus disease 2
• Fungal particles trapped in sinus cavityFungal particles trapped in sinus cavity• ““inside the sinus, outside the body”inside the sinus, outside the body”• Surgery to ventilate sinus is only part of Surgery to ventilate sinus is only part of
solutionsolution• Bacterial overgrowth in sinus cavityBacterial overgrowth in sinus cavity• Impairment in mucus, cilia functionImpairment in mucus, cilia function
Potential solutions - sinuses
• Topical delivery systemTopical delivery system• Implantable delivery systemImplantable delivery system• Slow-dissolving “gel” into sinus?Slow-dissolving “gel” into sinus?• Positive pressure aerosol?Positive pressure aerosol?• Other method of delivery Other method of delivery
• Long-term dosing directly to areaLong-term dosing directly to area• High topical dose, limited systemic absorptionHigh topical dose, limited systemic absorption• Constant dosingConstant dosing
Ear anatomy
Ear disease
• Middle earMiddle ear• Persistent effusionPersistent effusion• Recurrent infection or effusionRecurrent infection or effusion• Eustachian tube blockEustachian tube block
Ear disease
• Inner earInner ear – middle ear could be source of – middle ear could be source of drug deliverydrug delivery• Meniere’s disease (recurrent vertigo)Meniere’s disease (recurrent vertigo)• Autoimmune inner ear disease Autoimmune inner ear disease • Sudden hearing lossSudden hearing loss• Ototoxic systemic medicationsOtotoxic systemic medications• Noise traumaNoise trauma
Normal eardrum
Middle ear effusion
Issues – ear disease
• Easier accessEasier access• ProblemsProblems
• requires puncturing eardrumrequires puncturing eardrum• requires multiple procedures, dosesrequires multiple procedures, doses• long-term problems, want preventative long-term problems, want preventative
treatment in some cases treatment in some cases
Delivery system
• Prolonged releaseProlonged release• Steady dosing (not bolus)Steady dosing (not bolus)• Remain in situRemain in situ• Not interfere with hearingNot interfere with hearing
Summary
• Paranasal sinus and ear disease are very Paranasal sinus and ear disease are very common problemscommon problems
• Can get access to site of disease Can get access to site of disease • Need better long-term delivery and Need better long-term delivery and
distribution of medication dosesdistribution of medication doses