TY - JOUR

T1 - Mucoadhesive properties of nanogels based on stimuli-sensitive glycosaminoglycan-graft-pNIPAAm copolymers

AU - Pilipenko, Iuliia

AU - Korzhikov-Vlakh, Viktor

AU - Valtari, Annika

AU - Anufrikov, Yurii

AU - Kalinin, Stanislav

AU - Ruponen, Marika

AU - Krasavin, Mikhail

AU - Urtti, Arto

AU - Tennikova, Tatiana

N1 - Funding Information: This study was financially supported by Megagrant of the Government of Russian Federation (№ 075-15-2021-637 ) and Academy of Finland . The authors are grateful to Thermogravimetric and Сalorimetric Research Center of the Research Park of St. Petersburg State University. Publisher Copyright: © 2021

PY - 2021/9/1

Y1 - 2021/9/1

N2 - Mucoadhesive formulations capable of situ gelation are promising for improving ocular drug delivery. Here we investigated two types of nanogels based on anionic glycosaminoglycans with grafted thermo-responsive poly(N-isopropylacrylamide) chains. One type of nanogels were formed by thermo-induced gelling of heparin-graft-poly(N-isopropylacrylamide) and chondroitin sulfate-graft-poly(N-isopropylacrylamide) copolymers. Another type of nanogels was based on the same copolymers, but terminal groups of thermosensitive macromolecular chains were modified to form covalent disulfide cross-links. All types of nanogels were studied towards their ability to encapsulate and release model drug – dexamethasone. Mucoadhesivity of both thermo-gelled and covalently cross-linked polymeric systems, as well as their ability to interact with dexamethasone, was assessed by microscale thermophoresis (MST). Mucoadhesion properties were also evaluated by isothermal titration calorimetry (ITC), which were in good correlation with MST data. The presence of disulfide linkages and thiol groups were shown to favor improved binding of cross-linked nanogels to mucin. Moreover, in vivo intraocular pressure studies showed that presence of polymers in solution can alter the ocular absorption of carbonic anhydrase inhibitor from eyedrops. The pharmacological effect was in line with mucoadhesive properties of these copolymers.

AB - Mucoadhesive formulations capable of situ gelation are promising for improving ocular drug delivery. Here we investigated two types of nanogels based on anionic glycosaminoglycans with grafted thermo-responsive poly(N-isopropylacrylamide) chains. One type of nanogels were formed by thermo-induced gelling of heparin-graft-poly(N-isopropylacrylamide) and chondroitin sulfate-graft-poly(N-isopropylacrylamide) copolymers. Another type of nanogels was based on the same copolymers, but terminal groups of thermosensitive macromolecular chains were modified to form covalent disulfide cross-links. All types of nanogels were studied towards their ability to encapsulate and release model drug – dexamethasone. Mucoadhesivity of both thermo-gelled and covalently cross-linked polymeric systems, as well as their ability to interact with dexamethasone, was assessed by microscale thermophoresis (MST). Mucoadhesion properties were also evaluated by isothermal titration calorimetry (ITC), which were in good correlation with MST data. The presence of disulfide linkages and thiol groups were shown to favor improved binding of cross-linked nanogels to mucin. Moreover, in vivo intraocular pressure studies showed that presence of polymers in solution can alter the ocular absorption of carbonic anhydrase inhibitor from eyedrops. The pharmacological effect was in line with mucoadhesive properties of these copolymers.

KW - гепарин

KW - хондроитин сульфат

KW - поли(N-изопропил акриламид)

KW - доставка лекарств в глаза

KW - микромасштабный термофорез

KW - мукоадгезия

KW - ингибитор карбоангидразы

UR - http://www.scopus.com/inward/record.url?scp=85110606936&partnerID=8YFLogxK

U2 - 10.1016/j.ijbiomac.2021.07.070

DO - 10.1016/j.ijbiomac.2021.07.070

M3 - Article

AN - SCOPUS:85110606936

VL - 186

SP - 864

EP - 872

JO - International Journal of Biological Macromolecules

JF - International Journal of Biological Macromolecules

SN - 0141-8130

ER -