TY - JOUR
T1 - Hyaluronic Acid Graft Copolymers with Cleavable Arms as Potential Intravitreal Drug Delivery Vehicles
AU - Borke, Tina
AU - Najberg, Mathie
AU - Ilina, Polina
AU - Bhattacharya, Madhushree
AU - Urtti, Arto
AU - Tenhu, Heikki
AU - Hietala, Sami
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures.
AB - Treatment of retinal diseases currently demands frequent intravitreal injections due to rapid clearance of the therapeutics. The use of high molecular weight polymers can extend the residence time in the vitreous and prolong the injection intervals. This study reports a water soluble graft copolymer as a potential vehicle for sustained intravitreal drug delivery. The copolymer features a high molecular weight hyaluronic acid (HA) backbone and poly(glyceryl glycerol) (PGG) side chains attached via hydrolysable ester linkers. PGG, a polyether with 1,2-diol groups in every repeating unit available for conjugation, serves as a detachable carrier. The influence of synthesis conditions and incubation in physiological media on the molecular weight of HA is studied. The cleavage of the PGG grafts from the HA backbone is quantified and polymer-from-polymer release kinetics are determined. The biocompatibility of the materials is tested in different cell cultures.
KW - 116 Chemical sciences
KW - drug delivery vehicle
KW - hyaluronic acid
KW - poly(glyceryl glycerol)
KW - polymer-from-polymer release
KW - vitreous
U2 - 10.1002/mabi.201700200
DO - 10.1002/mabi.201700200
M3 - Article
SN - 1616-5187
VL - 18
JO - Macromolecular Bioscience
JF - Macromolecular Bioscience
IS - 1
M1 - 1700200
ER -