drug delivery systems michael g. stewart, md, mph professor and chairman department of...

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