Razvoj oftalmičkih nanoemulzija s kationskim lipidom cetiltrimetilamonijevim bromidom

master's thesis

• Title (english): Development of ophthalmic nanoemulsions with cationic lipid cetyltrimethylammonium bromide
• Author: Petra Parac
• Mentor: Jasmina Lovrić (mentor)
• Committee member: Jasmina Lovrić (predsjednik povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2022-08-31, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Bolest suhog oka najčešći je oblik kronične bolesti površine oka. Današnje su terapijske opcije ograničene, a lokalni kortikosteroidi, poput loteprednol etabonata, imaju potencijal za učinkovito liječenje blage do umjerene bolesti suhog oka. U posljednje vrijeme ističu se različiti terapijski nanosustavi za sigurnu i poboljšanu terapiju bolesti oka. U/V nanoemulzije niske su toksičnosti i iritacije te velikog kapaciteta za uklapanje lijekova slabo topljivih u vodi. Također, kationske nanoemulzije imaju sposobnost produljenja zadržavanja formulacije na površini oka temeljem interakcije s negativno nabijenim mucinima, a time posljedično i povećanja bioraspoloživosti lijeka.
U ovom je diplomskom radu proveden razvoj formulacije oftalmičke kationske nanoemulzije kao inovativni farmaceutski oblik s potencijalom primjene u liječenju bolesti suhog oka. Cilj diplomskog rada bio je razvoj formulacije kationskih U/V nanoemulzija prikladnih za uklapanje loteprednol etabonata. Nanoemulzije su pripravljene visokoenergetskom metodom mikrofluidizacije, a njihova karakterizacija je obuhvaćala određivanje veličine kapljica unutarnje faze, indeksa polidisperznosti i zeta-potencijala. Razvoj je proveden u četiri faze: probir vrste i udjela neionske površinski aktivne tvari, probir vrste lecitina, probir udjela lecitina te ispitivanje utjecaja dodatka kationskog lipida u formulaciji. Uspješno su pripravljene kationske nanoemulzije uljne faze Capryol™ 90 stabilizirane neionskom površinski aktivnom tvari Kolliphorom® EL, lecitinom Lipoidom® S75 te kationskim lipidom cetiltrimetilamonijevim bromidom (CTAB) kao nositeljem pozitivnog naboja. Rezultati pokazuju da visoke pozitivne vrijednosti zeta-potencijala pripravljenih nanoemulzija upućuju na odgovarajuću elektrostatsku stabilizaciju kationskim lipidom CTAB-om; Kolliphor® EL u formulaciji dodatno osigurava steričku stabilizaciju; Lipoid® S75 sadrži smjesu fosfolipida koji su sastavni dio prirodnog suznog filma i pridonose njegovoj stabilnosti.

Abstract (english)

Dry eye disease is the most common form of chronic ocular surface disease. Current therapy is limited, and topical corticosteroids such as loteprednol etabonate have the potential to effectively treat mild to moderate dry eye disease. Recently, various new therapeutic nanosystems have been highlighted for safe and improved treatment of eye diseases. O/W nanoemulsions are nontoxic and nonirritant and have a high capacity to incorporate poorly water-soluble drugs. Moreover, cationic nanoemulsions have the ability to prolong the retention on the surface of the eye due to interaction with negatively charged mucins, and consequently increase the bioavailability of the drug.
In this thesis, the development of the formulation of ophthalmic cationic nanoemulsion as an innovative pharmaceutical form with the potential in the treatment of dry eye disease was carried out. The aim of the thesis was the development of the formulation of cationic O/W nanoemulsions suitable for incorporating loteprednol etabonate. Nanoemulsions were prepared by microfluidization, and their characterization included the determination of the internal phase droplet size, polydispersity index and zeta-potential. The development was carried out in four phases: screening of the type and content of non-ionic surfactant, screening of the type of lecithin, screening of the lecithin content and screening of the cationic lipid content. Cationic nanoemulsions of oil phase Capryol™ 90 stabilized with nonionic surfactant Kolliphor® EL, lecithin Lipoid® S75 and cationic lipid cetyltrimethylammonium bromide (CTAB) as a positive charge carrier were successfully prepared. The results show that high positive zeta-potential values of the prepared nanoemulsions indicate adequate electrostatic stabilization by the cationic lipid CTAB; Kolliphor® EL in the formulation additionally provides steric stabilization; Lipoid® S75 contains a mixture of phospholipids that are an integral part of the natural tear film and contribute to its stability.

• Keywords: kationska nanoemulzija; bolest suhog oka; kationski lipid; cetiltrimetilamonijev bromid (CTAB); propilenglikol monokaprilat; makrogolglicerol ricinoleat 35; lecitin
• Keywords (english): cationic nanoemulsion; dry eye disease; cationic lipid; cetyltrimethylammonium bromide (CTAB); propylene glycol monocaprylate; macrogolglycerol ricinoleate 35; lecithin
• Language: croatian
• URN:NBN: urn:nbn:hr:163:228699
• 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: 2022-09-05 15:16:35