In vitro karakterizacija nazalnog praškastog sustava s natrijevim deksametazon fosfatom na Calu-3 staničnom modelu respiratornog epitela

master's thesis

• Title (english): In vitro characterisation of nasal powder delivery system of sodium dexamethasone phosphate using Calu-3 respiratory epithelial cell model
• Author: Iva Šimović
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner (predsjednik povjerenstva)
• Committee member: Maja Ortner Hadžiabdić (član povjerenstva)
• Committee member: Bisera Jurišić Dukovski (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2022-03-31, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Nazalna primjena lijekova istraţuje se u svrhu izravne dostave u središnji ţivčani sustav. Razvijanjem novih praškastih terapijskih sustava poboljšava se efikasnost takve primjene. U ranoj fazi razvoja ispituju se biokompatibilnost i utjecaj sustava na permeabilnost lijeka na in vitro modelima.
Cilj rada bio je pripremiti praškaste sustave mikrosfera s uklopljenim natrijevim deksametazon fosfatom (NDF-om) i inertnog nosača (laktoze i manitola) te odrediti osmolalnost disperzije sustava, kao i biokompatibilnost sustava te permeabilnost uklopljenog NDF-a korištenjem Calu-3 staničnog modela nazalnog epitela.
Metodom sušenja raspršivanjem uspješno su pripravljene mikrosfere graĎene od pektina i hipromeloze, sa sadrţajem uklopljenog NDF-a od 31,6 ± 1,5 %. Miješanjem mikrosfera s inertnim nosačem (laktozom i manitolom) u omjeru 1:9 (m/m) uspješno su pripravljeni praškasti sustavi. OdreĎena je osmolalnost disperzije sustava nakon suspendiranja u smjesi pročišćene vode i HBSS-Ca2+ (1:1, V/V). Vijabilnost Calu-3 staničnog modela nakon izlaganja ispitivanim sustavima bila je u rasponu od 81,5 ± 5,4 % do 113,8 ± 1,6 %. Manitol je pokazao bolja svojstva kao nosač u odnosu na laktozu. Za praškaste sustave s manitolom zabiljeţeno je reverzibilno smanjenje transepitelnog električnog otpora staničnog monosloja tijekom ispitivanja permeabilnosti te značajno veći prividni koeficijent permeabilnosti (Papp) NDF-a kroz Calu-3 stanični monosloj u odnosu na Papp NDF-a iz otopine.
Zaključno, pripravljeni praškasti sustav mikrosfera s uklopljenim NDF-om i manitolom kao inertnim nosačem pokazao je potencijal za nazalnu primjenu prema utvrĎenoj biokompatibilnosti i permeabilnosti lijeka in vitro.

Abstract (english)

Nasal drug administration is being examined as a direct delivery path to the central nervous system. The development of new powder drug delivery systems improves the effectiveness of such applications. Biompatibility and impact of system on drug permeability are evaluated early in the development using in vitro models.
The aim of this study was to prepare powder systems of microspheres with entrapped sodium dexamethasone phosphate (NDF) and inert carrier (lactose and mannitol), and to determine the osmolality of the dispersion of the systems, their biocompatibility and permeability of the incorporated NDF using a Calu-3 cell model of the nasal epithelium.
Microspheres made of pectin and hypromellose with a drug loading of 31.6 ± 1.5 %, were successfully prepared by spray-drying. Powder systems were successfully prepared by mixing microspheres with lactose and mannitol in ratio of 1:9 (w/w). The osmolality of the dispersion of powder systems was determined after suspending in a mixture of purified water and HBSS-Ca2+ (1:1, V/V). Calu-3 cell viability after exposure to the systems ranged from 81.5 ± 5.4 % to 113.8 ± 1.6 %. Mannitol showed better properties as the carrier compared to lactose. For systems with mannitol, a reversible decrease in transepithelial electrical resistance of the cell monolayer and significantly higher apparent permeability coefficient (Papp) of NDF across the Calu-3 monolayer in comparison to Papp of NDF in solution were observed.
In conclusion, prepared powder system composed of NDF loaded microspheres and mannitol showed potential for nasal administration considering determined in vitro biocompatibility and drug permeability.

• Keywords: nazalna primjena; praškasti sustavi; natrijev deksametazon fosfat; Calu-3; biokompatibilnost; permeabilnost
• Keywords (english): nasal delivery; powder systems; sodium dexamethasone phosphate; Calu-3; biocompatibility; permeability
• Language: croatian
• URN:NBN: urn:nbn:hr:163:102402
• 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: 2022-05-26 07:54:35