Development of ophthalmic secondary cationic nanoemulsions with chitosan oligosaccharide

Bolest suhog oka bolest je površine oka koja je u današnje vrijeme česta pojava. Češće se javlja kod starijih osoba, žena, osoba koje su izložene niskoj vlažnosti zraka, osoba s autoimunim poremećajima, ali i kod mlađih osoba zbog svakodnevne dugotrajne uporabe digitalnih uređaja. Kationske nanoemulzije sa svojstvom mukoadhezivnosti stupaju u kontakt s mucinima na površini oka i namijenjene su liječenju bolesti površine oka zbog duljeg zadržavanja lijeka i veće bioraspoloživosti. U liječenju simptoma blagog oblika bolesti suhog oka dobre rezultate pokazuju kationske nanoemulzije pripravljene od sastavnica sličnih onima koje su fiziološki prisutne na površini oka. U sklopu ovog diplomskog rada uspješno su pripravljene formulacije koje sadrže 2,5% (m/m) polusintetske smjese srednjelančanih triglicerida, 0,05% (m/m) lecitina, 0,25% (m/m) makrogolglicerol ricinoleata 35, 0,05% (m/m) kitozana – polusintetskog kationskog polimera sa svojstvom mukoadhezivnosti, 2,5% (m/m) glicerola – alkohola neutralnog naboja prikladnog za izotonizaciju nanoemulzija i pročišćenu vodu do 100% (m/m). Pripravljenim formulacijama ispitana su fizičko-kemijska svojstva: prosječna veličina, raspodjela veličina te zeta-potencijal kapljica unutarnje faze. Također, ispitano je svojstvo mukoadhezivnosti reološkom metodom te određivanjem veličine kapljica, raspodjele veličina kapljica i zeta-potencijala nanoemulzija nakon miješanja s mucinom. Na temelju provedenih ispitivanja kao formulacija s potencijalom za daljnji razvoj ističe se sekundarna kationska nanoemulzija s oligomerom kitozana pripravljena dodavanjem otopine oligomera kitozana u smjesu prije priprave nanoemulzije procesom mikrofluidizacije.Dry eye disease is an ocular surface disease common in present times, more expressed in certain populations, such as senior citizens, women, people exposed to low humidity, patients with autoimmune diseases as well as younger people due to excessive everyday use of digital devices. Cationic nanoemulsions of mucoadhesive properties interact with mucins on the ocular surface and are intended for treatment of ocular surface diseases due to longer retention time of the drug and consequently its greater bioavailability. In treating symptoms of mild form of dry eye disease, cationic nanoemulsions composed of components similar to those found as constituents of the ocular surface show good results. Formulations prepared for purposes of this diploma thesis are composed of 2.5% (w/w) semisynthetic mixture of middle chain fatty acids, 0.05% (w/w) lecithin, 0.25% (w/w) macrogolglycerol ricinoleate 35, 0.05% (w/w) chitosan – semisynthetic cationic polymer with mucoadhesive properties, 2.5% (w/w) glycerol – neutrally charged alcohol suitable for nanoemulsion isotonisation and purified water to 100% (w/w). Formulations were tested for their physicochemical properties: average size, size distribution as well as zeta-potential of droplets of inner phase of nanoemulsions. In addition, mucoadhesive properties were also tested using rheological method and by measuring droplet size, size distribution and zeta-potential of nanoemulsions after the addition of mucin. Based on all conducted tests, formulation showing the potential for further development is secondary cationic nanoemulsion with chitosan oligosaccharide formed by adding a solution of chitosan oligosaccharide to the mixture before the process of microfluidisation