Title Mukoadhezija farmaceutskih otopina koje sadrže natrijev hijaluronat - utjecaj koncentracije i molekulske mase natrijeva hijaluronata
Title (english) Mucoadhesion of pharmaceutical solutions containing sodium hyaluronate - influence of sodium hyaluronate concentration and molecular weight
Author Klara Strbad
Mentor Jasminka Giacometti (mentor)
Mentor Dijana Jureša (komentor)
Committee member Jasminka Giacometti (predsjednik povjerenstva)
Committee member Duško Čakara (član povjerenstva)
Committee member Jurica Novak (član povjerenstva)
Committee member Dijana Jureša (član povjerenstva)
Granter University of Rijeka (Faculty of Biotechnology and Drug Development) Rijeka
Defense date and country 2023-09-26, Croatia
Scientific / art field, discipline and subdiscipline BIOTECHNICAL SCIENCES Biotechnology
Abstract Otopine natrijeva hijaluronata koriste se kao umjetne suze koje vlaže i
regeneriraju oko. Natrijev hijaluronat kao polimer sastavljen od
ponavljajućih jedinica disaharida D-glukuronske kiseline i N-acetil-Dglukozamina pokazuje i mukoadhezivno svojstvo, što znači da stvara
interakciju s mucinom koji je sastavni dio sluznice na površini oka.
Stvarajući te interakcije produljuje se zadržavanje otopine na sluznici.
Svrha ovog rada je ispitati utjecaj faktora koji mogu povećati zadržavanje
otopine natrijeva hijaluronata na sluznici.
Ispitivalo se kako molekulska masa i koncentracija natrijeva hijaluronata u
otopini te osmolalnost otopine utječu na mukoadheziju otopina. Također,
ispitala su se reološka svojstva i osobine (viskoznost, pH, osmolalnost i
površinska napetost) otopina natrijeva hijaluronata različitih intrinzičnih
viskoznosti 0,6 m3/kg, 1,7 m3/kg i 2,3 m3/kg (odgovaraju redom
molekulskim masama 244 kDa, 980 kDa i 1420 kDa) triju masenih udjela:
0,21%; 0,4% i 0,6%, u hipotoničnim, izotoničnim i hipertoničnim uvjetima.
S povećanjem masenog udjela natrijeva hijaluronata, kao i s povećanjem
njegove molekulske mase viskoznosti otopina rastu, dok povećanje
osmolalnosti otopina smanjuje viskoznost neovisno o molekulskoj masi i
masenom udjelu natrijeva hijaluronata. Također ispitala se i stabilnost svih
otopina, nakon čuvanja na temperaturi od 50 °C tijekom tri mjeseca. U
svim slučajevima došlo je do pada viskoznosti otopina dok nije bilo
značajnih promjena drugih parametara.
Pomoću reoloških mjerenja na reometru, uz svinjski želučani mucin,
određen je relativni reološki sinergizam koji ukazuje postoji li interakcija
između otopine i mucina. Izotonične otopine intrinzičnih viskoznosti
natrijeva hijaluronata 1,7 m3/kg i 2,3 m3/kg s masenim udjelom od 0,4%
pokazale su interakciju s mucinom, dok otopina sa natrijevim hijaluronatom
najniže intrinzične viskoznosti 0,6 m3/kg nije pokazala interakciju. Bitno je
napomenuti da ta otopina je jedina pokazala Newtonovo reološko
ponašanje.
Porast osmolalnosti otopine pokazao je povećanje interakcije s mucinom
kao i povećanje masnog udjela natrijeva hijaluronata. Ovi su se utjecaji
ispitali na otopinama s natrijevim hijaluronatom intrinzične viskoznosti 1,7
m3/kg.
Interakciju s mucinom povećalo je veći maseni udio soli u otopini (veća
osmolalnost) i porast masenog udjela natrijeva hijaluronata, dok dobiveni
rezultati ne pokazuju proporcionalan odnos interakcije s mucinom i
molekulske mase natrijeva hijaluronata. Navedeno treba potvrditi
uključivanjem u ispitivanje više natrijevih hijaluronata u širem području
molekulskih masa (intrinzičnih viskoznost), te pomoću drugih metoda za
određivanje mukoadhezije.
Abstract (english) Sodium hyaluronate solutions are used as artificial tears that moisturize
and regenerate the eye. Sodium hyaluronate as a polymer composed of
repeating units of the disaccharide D-glucuronic acid and N-acetyl-Dglucosamine also exhibits mucoadhesive properties, which means that it
interacts with mucin, a part of the mucous membrane on the surface of the
eye. By creating these interactions, the retention of the solution on the
mucous membrane is prolonged. The purpose of this paper is to examine
the influence of factors that can increase retention on the mucous
membrane.
It was tested how the molecular weight and mass fraction of sodium
hyaluronate in the solution, and osmolality of the solution affect the
mucoadhesion of the solutions. Also, the rheological properties and
characteristics (viscosity, pH, osmolality and surface tension) of solutions
with different intrinsic viscosities of sodium hyaluronate 0.6 m3/kg, 1.7
m3/kg, and 2.3 m3/kg (respectively molecular weight ≈250 kDa, ≈980 kDa
and ≈1420 kDa) were tested in three mass fractions: 0.21%; 0.4% and
0.6%, in hypotonic, isotonic, and hypertonic conditions.
With an increase in the mass fraction of sodium hyaluronate, as well as
with an increase in its molecular weight, the viscosity of the solution
increases, while an increase in the osmolality of the solution decreases the
viscosity, regardless of the molecular weight and mass fraction of sodium
hyaluronate. The stability of all solutions was also tested after storage at
temperature 50 °C for three months. In all cases, there was a decrease in
the viscosity of the solutions, while there were no significant changes in
other parameters.
Using rheological measurements on a rheometer, relative rheological
synergism was determined with porcine gastric mucin, which indicates
whether there is an interaction between the solution and the mucin.
Isotonic solutions of sodium hyaluronate with intrinsic viscosities of 1.7
m3/kg and 2.3 m3/kg in a mass fraction of 0.4% showed interaction with
mucin, while the solution with sodium hyaluronate with the lowest intrinsic
viscosity of 0.6 m3/kg did not show interaction. It is important to note that
this solution was the only one that showed Newtonian rheological behavior.
The increase in the osmolality of the solution showed an increase in the
interaction with mucin as well as an increase in the mass fraction of sodium
hyaluronate. This influence was tested on solutions with sodium
hyaluronate with an intrinsic viscosity of 1.7 m3/kg.
The interaction with mucin increases with a higher mass fraction of salt in
the solution (higher osmolality) and an increase in the mass fraction of
sodium hyaluronate, while the obtained results do not show a proportional
relationship between the interaction with mucin and the molecular weight
of sodium hyaluronate. The above should be confirmed by including more
sodium hyaluronates in a wider range of molecular masses (intrinsic
viscosity) in the test, and by using other methods for determining
mucoadhesion.
Keywords
natrijev hijaluronat
viskoznost
mukoadhezija
reološke karakteristike
Keywords (english)
sodium hyaluronate
viscosity
mucoadhesion
rheological characteristics
Language croatian
URN:NBN urn:nbn:hr:193:831236
Study programme Title: Drug research and development Study programme type: university Study level: graduate Academic / professional title: magistar/magistra istraživanja i razvoja lijekova (magistar/magistra istraživanja i razvoja lijekova)
Type of resource Text
File origin Born digital
Access conditions Open access
Terms of use
Created on 2023-10-12 12:13:52