Razvoj oftalmičkih nanoemulzija sa stearilaminom

master's thesis

• Title (english): Development of ophtalmic nanoemulsions with stearylamin
• Author: Ana Bračko
• Mentor: Jasmina Lovrić (mentor)
• Committee member: Jasmina Lovrić (predsjednik povjerenstva)
• Committee member: Anita Hafner (član povjerenstva)
• Committee member: Dubravka Vitali Čepo (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical technology); Zagreb
• Defense date and country: 2019-07-12, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Razvoj topikalnih oftalmičkih pripravaka veliki je izazov zbog slabe topljivosti oftalmičkih djelatnih tvari
te anatomskih i fizioloških barijera oka. Jedan od rješenja za taj problem mogle bi biti nanoemulzije, koje
su relativno novi i još nedovoljno istraţeni terapijski sustavi. U svrhu ovog diplomskog rada izrađene su
kationske U/V nanoemulzije kojima je stearilamin nositelj pozitivnog naboja, a Kolliphor EL surfaktant
koji ih je dodatno sterički stabilizirao. Pozitivni naboj na površini uljnih kapljica s uklopljenom djelatnom
tvari, omogućuje kationskim nanoemulzijama produljeno zadržavanje, zahvaljujući elektrostatskim
interakcijama s negativno nabijenom površinom oka. U ovom diplomskom radu nanoemulzije sa
stearilaminom izrađene su pomoću mikrofluidizatora, a zatim su im bila ispitana fizičko-kemijska svojstva i
biokompatibilnost. Provedena su mjerenja koja su pokazala da povećanjem udjela stearilamina u
nanoemulzijama dolazi do povećanja veličine, indeksa polidisperznosti, zeta-potencijala i pH vrijednosti.
Isto tako, vrijednosti ispitivanih parametara su bile unutar odgovarajućih kriterija za oftalmičke pripravke.
Kako bi im se ispitala stabilnost provedena su ponovljena mjerenja istih parametara nakon 30 dana
skladištenja nanoemulzija pri 4 ºC, a rezultati su pokazali da su nanoemulzije zadržale stabilnost i
homogenost te da nisu pokazale značajnu promjenu u odnosu na mjerenja na dan izrade. Nanoemulzijama
je dokazana biokompatibilnost na višeslojnom in vitro modelu humanog epitela rožnice, pri čemu je
korištena HCE-T stanična linija uzgajana na Transwell® pločama, a vijabilnost modela je, nakon izlaganja
određena kolorimetrijskim MTT testom, iznosila oko 90%. Rezultati ovog istraživanja ukazuju na
potencijal primjene kationskih nanoemulzija sa stearilaminom kao tehnološkog oblika za uklapanje teško
topljivih oftalmičkih djelatnih tvari te njihovo produženo zadržavanje na površini oka bez štetnih učinaka.

Abstract (english)

The development of topical ophthalmic formulations is a major challenge due to the low solubility of ophthalmic
active substances and the anatomical and physiological barriers of the eye. One solution to this problem may be
development of nanoemulsions, which is a relatively new and insufficiently investigated drug delivery system.
For the purposes of this diploma thesis, cationic O/ W nanoemulsions were prepared, which included the
stearylamine as positively charged surfactant, and Kolliphor EL as surfactant which additionally sterically
stabilized them. Positive charge on the surface of the oil droplets with the active ingredient, allows cationic
nanoemulsions to improve drug retention, due to electrostatic interactions with the negatively charged surface of
the eye. In this diploma thesis the nanoemulsions with stearylamine were prepared using a microfluidizer and
then tested for their physiochemical properties and biocompatibility. With the increase in the content of
stearylamine in nanoemulsions increases the size, index of polydispersity, zeta-potentials and pH values.
Likewise, the values of the examined parameters were within the expected limits for ophthalmic formulations. In
order to test stability of prepared nanoemulsions, measurements of the same parameters were repeated after 30
days of storage of nanoemulsion at 4ºC, and the results showed that the nanoemulsions maintained their stability
and did not show a significant change in homogeneity compared to the measurements that were made on the day
of preparation. Nanoemulsions were shown to be biocompatable using the multilayer in vitro model of human
corneal epithelium, using a HCE-T cell line grown on Transwell® plates, and the viability of the model
determined with a colorimetric MTT test was approximately 90%. The results of this study indicate the potential
of cationic nanoemulsion with stearylamine as a delivery system for drugs with low water solubility and which
prolongs the drug retention on the surface of the eye without toxic effects.

• Keywords: nanoemulzija; mikrofluidizacija; stearilamin; Kolliphor EL; HCE-T stanična linija
• Keywords (english): nanoemulsion; microfluidisation; stearylamin; Kolliphor EL; HCE-T cell line
• Language: croatian
• URN:NBN: urn:nbn:hr:163:844354
• 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: 2020-02-12 13:06:14