Injectable peptide hydrogels for controlled-release of opioids

被引:31
作者
Martin, Charlotte [1 ]
Oyen, Edith [1 ]
Mangelschots, Jeroen [1 ]
Bibian, Mathieu [1 ]
Ben Haddou, Tanila [2 ,3 ]
Andrade, Jessica [4 ]
Gardiner, James [4 ]
Van Mele, Bruno [5 ]
Madder, Annemieke [6 ]
Hoogenboom, Richard [7 ]
Spetea, Mariana [2 ,3 ]
Ballet, Steven [1 ]
机构
[1] Vrije Univ Brussel, Res Grp Organ Chem, Pl Laan 2, B-1050 Brussels, Belgium
[2] Univ Innsbruck, Inst Pharm, Dept Pharmaceut Chem, Innrain 80-82, A-6020 Innsbruck, Austria
[3] Univ Innsbruck, Ctr Mol Biosci CMBI, Innrain 80-82, A-6020 Innsbruck, Austria
[4] CSIRO Mat Sci & Engn, Bayview Ave, Clayton, Vic 3169, Australia
[5] Vrije Univ Brussel, Phys Chem & Polymer Sci, Pl Laan 2, B-1050 Brussels, Belgium
[6] Univ Ghent, Organ & Biomimet Chem Res Grp, Krijgslaan 281, B-9000 Ghent, Belgium
[7] Univ Ghent, Supramol Chem Grp, Krijgslaan 281, B-9000 Ghent, Belgium
基金
奥地利科学基金会;
关键词
DRUG-DELIVERY SYSTEMS; CHRONIC PAIN; EXTENDED-RELEASE; CANCER PAIN; MANAGEMENT; FORMULATION; EFFICACY; DESIGN; BACK;
D O I
10.1039/c5md00440c
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Herein, a family of hydrogel-forming peptides was designed starting from the short, tunable and amphipathic hexapeptide hydrogelator H-Phe-Glu-Phe-Gln-Phe-Lys-OH (1). The hydrophobic side chains as well as the nature of both N- and C-termini were modified in order to obtain suitable gelation conditions and drug release profiles for in vivo application. To potentially increase the enzymatic stability, an all-D analogue was prepared as well. After their macroscopic and microscopic characterization by rheology and transmission electron microscopy (TEM) analysis, opioid drugs were encapsulated into the hydrogels and sustained release experiments were carried out. Hydrogel toxicity was assessed in cell viability assays. Based on the physicochemical, mechanical, and noncytotoxic properties, H-Phe-Glu-Phe-Gln-Phe-Lys-NH2 (2) was further investigated for in vivo release of morphine. The antinociceptive effects following subcutaneous injection of the morphine-containing hydrogel 2 was evaluated in a model of thermal nociception using the mouse tail-flick test. Sustained antinociceptive effects over extended periods of time (up to 24 h) for morphine co-formulated with hydrogel 2, compared to morphine injection in solution (effects up to 2 h), were observed.
引用
收藏
页码:542 / 549
页数:8
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