Design of Bio-Responsive Hyaluronic Acid-Doxorubicin Conjugates for the Local Treatment of Glioblastoma

被引：26
作者：
Malfanti, Alessio [1 ]
Catania, Giuseppina [1 ]
Degros, Quentin [1 ]
Wang, Mingchao [1 ]
Bausart, Mathilde [1 ]
Preat, Veronique [1 ]
机构：
[1] Univ Louvain, Adv Drug Delivery & Biomat, Louvain Drug Res Inst, B-1200 Brussels, Belgium
来源：
PHARMACEUTICS | 2022年 / 14卷 / 01期
关键词：
glioblastoma; local treatment; hyaluronic acid; polymer-drug conjugates; bio-responsive linkers; COMBINATION THERAPY; DRUG; DELIVERY; EFFICACY; TEMOZOLOMIDE; MICELLES; NANOPARTICLES; NANOCARRIERS; RADIOTHERAPY; GEMCITABINE;
D O I：
10.3390/pharmaceutics14010124
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Glioblastoma is an unmet clinical need. Local treatment strategies offer advantages, such as the possibility to bypass the blood-brain barrier, achieving high drug concentrations at the glioblastoma site, and consequently reducing systemic toxicity. In this study, we evaluated the feasibility of using hyaluronic acid (HA) for the local treatment of glioblastoma. HA was conjugated to doxorubicin (DOX) with distinct bio-responsive linkers (direct amide conjugation HA-NH-DOX), direct hydrazone conjugation (HA-Hz-DOX), and adipic hydrazone (HA-AdpHz-DOX). All HA-DOX conjugates displayed a small size (less than 30 nm), suitable for brain diffusion. HA-Hz-DOX showed the best performance in killing GBM cells in both 2D and 3D in vitro models and displayed superior activity in a subcutaneous GL261 tumor model in vivo compared to free DOX and other HA-DOX conjugates. Altogether, these results demonstrate the feasibility of HA as a polymeric platform for the local treatment of glioblastoma and the importance of rationally designing conjugates.
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页数：16
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