Ispitivanje bioadhezivnosti lecitinsko-kitozanskih nanočestica s melatoninom

master's thesis

• Title (english): Evaluation of bioadhesive properties of melatonin-loaded lechitin/chitosan nanoparticles
• Author: Maja Brkić
• Mentor: Anita Hafner (mentor)
• Committee member: Anita Hafner
• Committee member: Jasmina Lovrić
• Committee member: Dubravka Vitali Čepo
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2015-09-25, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Topikalna primjena glavni je put primjene oftalmičkih lijekova, budući da je zbog jednostavnosti i neinvazivnosti najbolje prihvaćena od bolesnika. Istodobno, barijere prednjeg segmenta oka ograničavaju vrijeme zadržavanja pripravka na površini oka te brzinu i obim apsorpcije, rezultirajući malom bioraspoloživošću lijeka u oku. Suvremena istraživanja usmjerena su na razvoj terapijskih nanosustava za topikalnu oftalmičku primjenu s ciljem produljenja kontakta sustava s površinom oka, kontroliranja kinetike oslobađanja lijeka iz sustava i poboljšanja bioraspoloživosti lijeka u oku. U ovom radu pripravljene su lecitinsko-kitozanske nanočestice kao terapijski sustav namijenjen za oftalmičku primjenu melatonina. Melatonin je hormon epifize kojemu je jedna od brojnih funkcija i sniženje povišenog očnog tlaka. Cilj ovog rada bio je ispitati bioadhezivnost lecitinsko-kitozanskih nanočestica s melatoninom in vitro, odnosno procijeniti njihov potencijal da produlje vrijeme zadržavanja melatonina u prekornealnom području i osiguraju njegovu veću bioraspoloživost u oku. Lecitinsko-kitozanske nanočestice srednjeg promjera od 252,2 ± 2,7 nm, pozitivnog zeta-potencijala (24,6 ± 1,1 mV) te zadovoljavajućeg sadržaja melatonina (5,4 ± 0,2 %) uspješno su pripravljene ionskom interakcijom lecitina i kitozana. Srednji promjer lecitinskih nanočestica bio je značajno manji (94,6 ± 2,8 nm) od promjera odgovarajućih lecitinsko-kitozanskih nanočestica, dok im je zeta-potencijal bio negativan (-35,0 ± 3,9 mV). Bioadhezivnost nanočestica ispitana je određivanjem njihovog prianjanja na konfluentni sloj imortaliziranih stanica humanog epitela rožnice (HCE-T). Uočena je znatno veća bioadhezivnost lecitinsko-kitozanskih nanočestica s melatoninom u odnosu na bioadhezivnost lecitinskih nanočestica, koja proizlazi iz razlike u njihovom površinskom naboju. Dobiveni rezultati podupiru potencijalnu topikalnu oftalmičku primjenu lecitinsko-kitozanskih nanočestica kao nosača melatonina s ciljem osiguranja veće bioraspoloživosti melatonina u oku i boljeg terapijskog učinka na povišeni očni tlak.

Abstract (english)

Ophthalmic drugs are mostly applied by topical route of administration, since, being simple and non-invasive, it represents the most convenient route for the patients. However, barriers of the anterior segment of the eye limit the retention time of the formulation at the surface of the eye, as well as the rate and extent of absorption, resulting in low eye-related drug bioavailability. Current investigations are focused on the development of ophthalmic drug delivery systems for topical administration, with the aim to ensure prolonged drug contact with the surface of the eye, controlled drug release kinetics and improved eye-related bioavailability. In this study, lecithin/chitosan nanoparticles as ophthalmic delivery system for melatonin topical administration were prepared. Melatonin is pineal hormone with pleiotropic effects among which is the regulation of increased intraocular pressure. The aim of this study was to investigate bioadhesion of melatonin-loaded lecithin/chitosan nanoparticles in vitro, in order to assess their potential to prolong melatonin retention time at the precorneal area and to ensure melatonin improved eye-related bioavailability. Lecithin/chitosan nanoparticles with mean diameter of 252.2 ± 2.7 nm, positive zeta potential (24.6 ± 1.1 mV) and appropriate melatonin content (5.4 ± 0.2 %) were successfully prepared by ionic interaction between lecithin and chitosan. Mean diameter of lecithin nanoparticles was significantly lower (94.6 ± 2.8 nm) than the mean diameter of corresponding lecithin/chitosan nanoparticles, and their zeta potential was negative (-35.0 ± 3.9 mV). Bioadhesion of nanoparticles was assessed by monitoring their adhesion to confluent monolayer of immortalised human corneal epithelial cells (HCE-T). Significantly higher extent of bioadhesion was observed in case of melatonin-loaded lecithin/chitosan nanoparticles compared to lecithin nanoparticles, which was ascribed to the difference in their surface charge. The results obtained support the potential topical ophthalmic administration of lecithin/chitosan nanoparticles as melatonin nanocarriers, with the aim to ensure improved eye-related melatonin bioavailability and improved regulation of increased intraocular pressure.

• Keywords: kitozan; melatonin; lecitin; bioadhezivnost; nanočestice; oftalmička primjena
• Keywords (english): chitosan; melatonin; lecithin; bioadhesion; nanoparticles; ocular delivery
• Language: croatian
• URN:NBN: urn:nbn:hr:163:413419
• 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: 2016-02-18 16:08:15