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Multilayered Thin Films from Boronic Acid-Functional Poly(amido amine)s.

Hujaya SD, Engbersen JF, Paulusse JM - Pharm. Res. (2015)

Bottom Line: Biocompatibility of the resulting films was evaluated through cell culture experiments with COS-7 cells grown on the films.All of the multilayers are stable under physiological conditions in vitro and are responsive to reducing agents, owing to the presence of disulfide bonds in the polymers.Graphical Abstract Layer-by-Layer Assembly.

View Article: PubMed Central - PubMed

Affiliation: Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE, Enschede, The Netherlands.

ABSTRACT

Purpose: To investigate the properties of phenylboronic acid-functional poly(amido amine) polymers (BA-PAA) in forming multilayered thin films with poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their compatibility with COS-7 cells.

Methods: Copolymers of phenylboronic acid-functional poly(amido amine)s, differing in the content of primary amine (DAB-BA-PAA) or alcohol (ABOL-BA-PAA) side groups, were synthesized and applied in the formation of multilayers with PVA and ChS. Biocompatibility of the resulting films was evaluated through cell culture experiments with COS-7 cells grown on the films.

Results: PVA-based multilayers were thin, reaching ~100 nm at 10 bilayers, whereas ChS-based multilayers were thick, reaching ~600 nm at the same number of bilayers. All of the multilayers are stable under physiological conditions in vitro and are responsive to reducing agents, owing to the presence of disulfide bonds in the polymers. PVA-based films were demonstrated to be responsive to glucose at physiological pH at the investigated glucose concentrations (10-100 mM). The multilayered films displayed biocompatibility in cell culture experiments, promoting attachment and proliferation of COS-7 cells.

Conclusions: Responsive thin films based on boronic acid functional poly(amido amine)s are promising biocompatible materials for biomedical applications, such as drug releasing surfaces on stents or implants. Graphical Abstract Layer-by-Layer Assembly.

No MeSH data available.


Related in: MedlinePlus

Reaction scheme for the synthesis of monomer 4AMPBA.
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Sch3: Reaction scheme for the synthesis of monomer 4AMPBA.

Mentions: Syntheses of the BA-PAAs started with the synthesis of the BA-functional monomer. The monomer 4AMPBA was synthesized as illustrated in Scheme 3. The reaction started with the formation of imine between NBDAB and 4FPBA under nitrogen atmosphere. After 1 day, the light yellow transparent solution turned slightly brown indicating formation of imine which lengthens the double-bond conjugation in the new compound. This newly formed imine bond was reacted with excess of NaBH4 upon which the color of the solution turned yellowish again. This color change indicates that the conjugation length in the product is decreased, which is in accordance with the reduction of the imine bond. After isolation under reduced pressure, the product was further purified via extraction in DCM/water mixture. The product dissolved more readily in the organic DCM phase while the charged borate salt that was formed as side product dissolved more readily in the aqueous phase. Deprotection by treatment of the product in methanol with HCl gas readily yielded the final product in its HCl salt form. 1H-NMR showed the disappearance of the 9-proton singlet in 1.4 ppm which indicated complete deprotection. Following exhaustive lyophilization, the purity of the product was confirmed using a known amount of N,N-dimethylformamide as internal standard in 1H-NMR sample characterization to be roughly 90–94%.Scheme 3


Multilayered Thin Films from Boronic Acid-Functional Poly(amido amine)s.

Hujaya SD, Engbersen JF, Paulusse JM - Pharm. Res. (2015)

Reaction scheme for the synthesis of monomer 4AMPBA.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4526598&req=5

Sch3: Reaction scheme for the synthesis of monomer 4AMPBA.
Mentions: Syntheses of the BA-PAAs started with the synthesis of the BA-functional monomer. The monomer 4AMPBA was synthesized as illustrated in Scheme 3. The reaction started with the formation of imine between NBDAB and 4FPBA under nitrogen atmosphere. After 1 day, the light yellow transparent solution turned slightly brown indicating formation of imine which lengthens the double-bond conjugation in the new compound. This newly formed imine bond was reacted with excess of NaBH4 upon which the color of the solution turned yellowish again. This color change indicates that the conjugation length in the product is decreased, which is in accordance with the reduction of the imine bond. After isolation under reduced pressure, the product was further purified via extraction in DCM/water mixture. The product dissolved more readily in the organic DCM phase while the charged borate salt that was formed as side product dissolved more readily in the aqueous phase. Deprotection by treatment of the product in methanol with HCl gas readily yielded the final product in its HCl salt form. 1H-NMR showed the disappearance of the 9-proton singlet in 1.4 ppm which indicated complete deprotection. Following exhaustive lyophilization, the purity of the product was confirmed using a known amount of N,N-dimethylformamide as internal standard in 1H-NMR sample characterization to be roughly 90–94%.Scheme 3

Bottom Line: Biocompatibility of the resulting films was evaluated through cell culture experiments with COS-7 cells grown on the films.All of the multilayers are stable under physiological conditions in vitro and are responsive to reducing agents, owing to the presence of disulfide bonds in the polymers.Graphical Abstract Layer-by-Layer Assembly.

View Article: PubMed Central - PubMed

Affiliation: Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology and Technical Medicine, Faculty of Science and Technology, University of Twente, P.O. Box 217, 7500 AE, Enschede, The Netherlands.

ABSTRACT

Purpose: To investigate the properties of phenylboronic acid-functional poly(amido amine) polymers (BA-PAA) in forming multilayered thin films with poly(vinyl alcohol) (PVA) and chondroitin sulfate (ChS), and to evaluate their compatibility with COS-7 cells.

Methods: Copolymers of phenylboronic acid-functional poly(amido amine)s, differing in the content of primary amine (DAB-BA-PAA) or alcohol (ABOL-BA-PAA) side groups, were synthesized and applied in the formation of multilayers with PVA and ChS. Biocompatibility of the resulting films was evaluated through cell culture experiments with COS-7 cells grown on the films.

Results: PVA-based multilayers were thin, reaching ~100 nm at 10 bilayers, whereas ChS-based multilayers were thick, reaching ~600 nm at the same number of bilayers. All of the multilayers are stable under physiological conditions in vitro and are responsive to reducing agents, owing to the presence of disulfide bonds in the polymers. PVA-based films were demonstrated to be responsive to glucose at physiological pH at the investigated glucose concentrations (10-100 mM). The multilayered films displayed biocompatibility in cell culture experiments, promoting attachment and proliferation of COS-7 cells.

Conclusions: Responsive thin films based on boronic acid functional poly(amido amine)s are promising biocompatible materials for biomedical applications, such as drug releasing surfaces on stents or implants. Graphical Abstract Layer-by-Layer Assembly.

No MeSH data available.


Related in: MedlinePlus