In vitro ispitivanje nazalne depozicije mikrosfera s donepezilom

master's thesis

• Title (english): In vitro evaluation of nasal deposition of donepezil-loaded microspheres
• Author: Tamara Topalović
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Committee member: Ivan Pepić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2022-06-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Alzheimerova bolest (AB) je kronična i progresivna bolest središnjeg živčanog sustava (SŽS) s kompleksnim patološkim mehanizmima u podlozi. Glavna skupina lijekova koji se koriste u liječenju AB-a su inhibitori acetilkolinesteraze (donepezil, rivastigmin, galantamin). Unatoč velikom napretku u neuroznanosti i novim neuroterapeuticima, učinkovitost liječenja bolesti SŽS-a je ograničena postojanjem krvno moždane barijere. Iz tog
razloga je smanjena učinkovitost sistemski primijenjenog lijeka u mozgu. Nazalna primjena lijekova pruža
mogućnost izravne dostave u SŽS. Odlikuju ju brz nastup djelovanja, neinvazivnost te zaobilaženje probavnog sustava i prvog prolaska kroz jetru. Cilj ovog rada bio je pripraviti i karakterizirati mikrosfere s donepezilom građene od kitozana i manitola te ispitati utjecaj parametara primjene (kut primjene u odnosu na horizontalnu ravninu i protok udahnutog zraka) na nazalnu depoziciju pripravljenih mikrosfera. Mikrosfere s donepezilom
zadovoljile su kriterije za primjenu u nosnoj šupljini s obzirom na prikladnu uspješnost uklapanja, sadržaj lijeka,
sadržaj vlage, površinski naboj i reološka svojstva. Pri ispitivanju depozicije u nosnoj šupljini, korišten je 3D
printani model nosne šupljine, respiratorna pumpa (za simulaciju disanja) i UDSP uređaj razvijen za ciljanje olfaktorne regije. Mikrosfere s donepezilom uspješno su dostavljene u ciljnu (olfaktornu) regiju nosne šupljine. Smanjenjem kuta primjene uređaja u odnosu na horizontalnu ravninu rastao je udio lijeka dostavljen u olfaktornu
regiju. Primjena UDSP uređaja uz zadržavanje daha rezultirala je većom depozicijom lijeka u ciljnoj olfaktornoj
regiji, te manjom depozicijom u anteriornoj i posteriornoj regiji, u odnosu na primjenu uz udah.

Abstract (english)

Alzheimer’s disease (AD) is a chronic and progressive disease of the central nervous system (CNS) with complex underlying pathological mechanisms. The main group of medications used in the AD treatment are acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine). Despite great advances in neuroscience and
new neurotherapeutics, the effectiveness of CNS disease treatment is primarily limited by the existence of a bloodbrain barrier. Thus, brain bioavailability of a systemically administrated drug is reduced. Nasal administration
enables direct CNS delivery of the drug. It is characterized by rapid onset of action, non-invasiveness, bypass of the gastrointestinal tract and first-pass metabolism. The aim of this study was to prepare and characterize
chitosan/mannitol based donepezil-loaded microspheres and to examine the influence of administration parameters
(administration angle in relation to the horizontal plane and inspiratory flow rate) on nasal deposition of prepared microspheres. Donepezil-loaded microspheres met the criteria for nasal application with respect to appropriate entrapment efficiency, drug loading, moisture content, surface charge, and rheological properties. In nasal deposition studies, a 3D printed nasal cavity model, a respiratory pump (for simulating breathing) and a UDSP
delivery device were used. Donepezil-loaded microspheres were successfully delivered to the targeted (olfactory)
region of the nasal cavity. By reducing the administration angle in relation to the horizontal plane, the proportion of drug delivered to the olfactory region increased. The use of the device at breath-hold resulted in higher drug
deposition in the targeted olfactory region, and lower deposition in the anterior and posterior regions, compared to
application under breathing conditions.

• Keywords: nazalna primjena; donepezil; mikrosfere; nazalna depozicija; model nosne šupljine
• Keywords (english): nasal drug administration; donepezil; microspheres; nasal deposition; nasal cast
• Language: croatian
• URN:NBN: urn:nbn:hr:163:887580
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-07-13 10:22:30