Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex

Amorphous drug-polyanion nanoplex represents an effective solubility enhancement strategy of weakly-basic poorly-soluble drugs. While dextran sulfate (DXT) was chosen in most studies as the polyanion for nanoplex formation, drug-DXT nanoplex demonstrated poor long-term physical stability for drugs w...

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Main Authors: Dong, Bingxue, Hadinoto, Kunn
Other Authors: School of Chemical and Biomedical Engineering
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/141832
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1418322020-06-22T03:40:32Z Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex Dong, Bingxue Hadinoto, Kunn School of Chemical and Biomedical Engineering Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex Engineering::Chemical engineering Cellulose Polyelectrolyte Complex Amorphous drug-polyanion nanoplex represents an effective solubility enhancement strategy of weakly-basic poorly-soluble drugs. While dextran sulfate (DXT) was chosen in most studies as the polyanion for nanoplex formation, drug-DXT nanoplex demonstrated poor long-term physical stability for drugs with high crystallization propensity, such as ciprofloxacin (CIP). Herein we hypothesized that amorphous form stability of CIP nanoplex could be improved by substituting DXT with carboxymethyl cellulose (CMC) known for its crystallization inhibiting activity. The optimal preparation condition of the CIP-CMC nanoplex was determined by investigating the effects of CMC/CIP charge ratio and pH on the resultant nanoplex's physical characteristics and preparation efficiency. At the optimal condition, the CIP-CMC nanoplex possessed size, zeta potential, and CIP payload of approximately 200 nm, -49 mV, and 76%, respectively. Its preparation was highly efficient with CIP utilization rate and overall yield of roughly 89% and 46%, respectively. Compared to the CIP-DXT nanoplex, the CIP-CMC nanoplex was larger and with higher CIP payload attributed to CMC's higher chain stiffness. The CIP-CMC nanoplex exhibited superior physical stability after twelve-month storage and improved solubility enhancement capability (30% higher), despite its slower dissolution. These results clearly established CMC as the superior polyanion to DXT for nanoplex formation of weakly-basic drugs. 2020-06-11T03:16:45Z 2020-06-11T03:16:45Z 2019 Journal Article Dong, B., & Hadinoto, K. (2019). Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex. International journal of biological macromolecules, 139, 500-508. doi:10.1016/j.ijbiomac.2019.08.023 0141-8130 https://hdl.handle.net/10356/141832 10.1016/j.ijbiomac.2019.08.023 31386874 2-s2.0-85073707067 139 500 508 en International journal of biological macromolecules © 2019 Elsevier B.V. All rights reserved.
institution Nanyang Technological University
building NTU Library
country Singapore
collection DR-NTU
language English
topic Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
Engineering::Chemical engineering
Cellulose
Polyelectrolyte Complex
spellingShingle Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
Engineering::Chemical engineering
Cellulose
Polyelectrolyte Complex
Dong, Bingxue
Hadinoto, Kunn
Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
description Amorphous drug-polyanion nanoplex represents an effective solubility enhancement strategy of weakly-basic poorly-soluble drugs. While dextran sulfate (DXT) was chosen in most studies as the polyanion for nanoplex formation, drug-DXT nanoplex demonstrated poor long-term physical stability for drugs with high crystallization propensity, such as ciprofloxacin (CIP). Herein we hypothesized that amorphous form stability of CIP nanoplex could be improved by substituting DXT with carboxymethyl cellulose (CMC) known for its crystallization inhibiting activity. The optimal preparation condition of the CIP-CMC nanoplex was determined by investigating the effects of CMC/CIP charge ratio and pH on the resultant nanoplex's physical characteristics and preparation efficiency. At the optimal condition, the CIP-CMC nanoplex possessed size, zeta potential, and CIP payload of approximately 200 nm, -49 mV, and 76%, respectively. Its preparation was highly efficient with CIP utilization rate and overall yield of roughly 89% and 46%, respectively. Compared to the CIP-DXT nanoplex, the CIP-CMC nanoplex was larger and with higher CIP payload attributed to CMC's higher chain stiffness. The CIP-CMC nanoplex exhibited superior physical stability after twelve-month storage and improved solubility enhancement capability (30% higher), despite its slower dissolution. These results clearly established CMC as the superior polyanion to DXT for nanoplex formation of weakly-basic drugs.
author2 School of Chemical and Biomedical Engineering
author_facet School of Chemical and Biomedical Engineering
Dong, Bingxue
Hadinoto, Kunn
format Article
author Dong, Bingxue
Hadinoto, Kunn
author_sort Dong, Bingxue
title Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
title_short Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
title_full Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
title_fullStr Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
title_full_unstemmed Carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
title_sort carboxymethyl cellulose is a superior polyanion to dextran sulfate in stabilizing and enhancing the solubility of amorphous drug-polyelectrolyte nanoparticle complex
publishDate 2020
url https://hdl.handle.net/10356/141832
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