Long-term delivery of growth factors and immunomodulatory agents is highly required to support the integrity of tissue in engineering constructs, e.g., formation of vasculature, and to minimize immune response in a recipient. However, for proteins with a net positive charge at the physiological pH, controlled delivery from negatively charged alginate (Alg) platforms is challenging due to electrostatic interactions that can hamper the protein release. In order to regulate such interactions between proteins and the Alg matrix, we propose to complex proteins of interest in this study - CXCL12, FGF-2, VEGF - with polyanionic heparin prior to their encapsulation into Alg microbeads of high content of α-L-guluronic acid units (high-G). This strategy effectively reduced protein interactions with Alg (as shown by model ITC and SPR experiments) and, depending on the protein type, afforded control over the protein release for at least one month. The released proteins retained their in vitro bioactivity: CXCL12 stimulated the migration of Jurkat cells, and FGF-2 and VEGF induced proliferation and maturation of HUVECs. The presence of heparin also intensified protein biological efficiency. The proposed approach for encapsulation of proteins with a positive net charge into high-G Alg hydrogels is promising for controlled long-term protein delivery under in vivo conditions.

• MeSH
• algináty chemie   MeSH
• chemokin CXCL12 chemie   MeSH
• endoteliální buňky pupečníkové žíly (lidské) MeSH
• fibroblastový růstový faktor 2 chemie   MeSH
• heparin chemie   MeSH
• lidé MeSH
• mikrosféry MeSH
• nádorové buněčné linie MeSH
• tkáňové inženýrství MeSH
• vaskulární endoteliální růstový faktor A chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH

Among external stimuli used to trigger release of a drug from a polymeric carrier, ultrasound has gained increasing attention due to its non-invasive nature, safety and low cost. Despite this attention, there is only limited knowledge about how materials available for the preparation of drug carriers respond to ultrasound. This study investigates the effect of ultrasound on the release of a hydrophobic drug, dexamethasone, from poly(2-oxazoline)-based micelles. Spontaneous and ultrasound-mediated release of dexamethasone from five types of micelles made of poly(2-oxazoline) block copolymers, composed of hydrophilic poly(2-methyl-2-oxazoline) and hydrophobic poly(2-n-propyl-2-oxazoline) or poly(2-butyl-2-oxazoline-co-2-(3-butenyl)-2-oxazoline), was studied. The release profiles were fitted by zero-order and Ritger-Peppas models. The ultrasound increased the amount of released dexamethasone by 6% to 105% depending on the type of copolymer, the amount of loaded dexamethasone, and the stimulation time point. This study investigates for the first time the interaction between different poly(2-oxazoline)-based micelle formulations and ultrasound waves, quantifying the efficacy of such stimulation in modulating dexamethasone release from these nanocarriers.

• MeSH
• dexamethason farmakokinetika   MeSH
• dynamický rozptyl světla MeSH
• hydrofobní a hydrofilní interakce MeSH
• lékové transportní systémy metody   MeSH
• micely MeSH
• nosiče léků chemie   farmakokinetika   MeSH
• oxazoly chemie   MeSH
• polymery chemie   MeSH
• transmisní elektronová mikroskopie MeSH
• ultrazvuk metody   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH