Interpenetrating polymer network (IPN)-based bead formulations were exploited by cross-linking different hydrophilic polymers in different combinations and at different ratios. Polyvinyl alcohol, xanthan gum, guar gum, gellan gum, and sodium alginate (Na-alginate) were used in this work as hydrophilic polymers to enhance the solubility of diclofenac sodium and also to target the delivery at preferred locations. IPN beads based on polysaccharides were prepared by the ionic gelation method. Differential scanning calorimetry, powder X-ray diffraction, scanning electron microscopy, and Fourier transform infrared spectroscopy data showed that the IPN microbeads solubilized and encapsulated the drug within the network. We found over 83% encapsulation efficiency of the drug delivery system for the drug, and this efficiency increased with the concentration of the polymer. Ex vivo experiments using the goat intestine revealed that the IPN microbeads were able to adhere to the intestinal epithelium, a mucoadhesive behavior that could be beneficial to the drug pharmacokinetics, while in vitro experiments in phosphate buffer showed that the IPN enabled significant drug release. We believe that these IPN microbeads are an excellent drug delivery system to solubilize drug molecules and ensure adhesion to the intestinal wall, thereby localizing the drug release to enhance bioavailability of poorly soluble drugs.

• Publikační typ
• časopisecké články MeSH

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.

• Klíčová slova
• CXCL12, FGF-2, HUVECs, ITC, SPR, VEGF, alginate microbeads, bioactivity, heparin, protein release,
• 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
• Názvy látek
• algináty MeSH
• chemokin CXCL12 MeSH
• fibroblastový růstový faktor 2 MeSH
• heparin MeSH
• vaskulární endoteliální růstový faktor A MeSH