Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight
Polyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are benefici...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-07-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/7/1403 |
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| author | Radhakanta Ghosh Yuvaraj Arun Peter Siman Abraham J. Domb |
| author_facet | Radhakanta Ghosh Yuvaraj Arun Peter Siman Abraham J. Domb |
| author_sort | Radhakanta Ghosh |
| collection | DOAJ |
| description | Polyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are beneficial to hinder the characteristic hydrolytic cleavage of an anhydride bond that provides stable polyanhydrides at room temperature. The objective of this work is to synthesize aliphatic polyanhydrides with various hydrophobic segments, controllable and reproducible molecular weight, and low polydispersity that are essential for potential use as drug carriers. A series of polyanhydrides of suberic, azelaic, sebacic, and dodecanedioic acids with controlled molecular weight, reduced polydispersity, and standard deviation of molecular weights, have been synthesized. All synthesized polyanhydrides were thoroughly characterized by NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography. Molecular weights of the synthesized polyanhydrides are highly controllable, depending on the degree of activation of the dicarboxylic acid monomers, i.e., the amount of acetic anhydride used during synthesis. Polyanhydrides have been synthesized in triplicate by melt-polycondensation, using various mole ratios of acetic anhydride to diacids. The standard deviation of the molecular weights of the polyanhydrides is minute when using 1 equivalent of acetic anhydride during the activation of dicarboxylic acids, whereas if excess acetic anhydride is used, the standard deviation is very high. The effect of safe and natural inorganic catalysts, Calcium oxide, Zinc oxide, and Calcium carbonate on polymerization is also studied. As-synthesized poly(sebacic acid) can offer convenience to use in controlled drug delivery applications. In vitro drug release study using Temozolamide (TMZ), a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma, shows 14% TMZ release after the first hour and 70% release over one day from the poly(sebacic acid) wafers. |
| first_indexed | 2024-03-09T10:13:25Z |
| format | Article |
| id | doaj.art-64bf530969ce4215970299362ac75173 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T10:13:25Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-64bf530969ce4215970299362ac751732023-12-01T22:34:23ZengMDPI AGPharmaceutics1999-49232022-07-01147140310.3390/pharmaceutics14071403Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular WeightRadhakanta Ghosh0Yuvaraj Arun1Peter Siman2Abraham J. Domb3The Alex Grass Center for Drug Design and Synthesis and Center for Cannabis Research, School of Pharmacy, Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelThe Alex Grass Center for Drug Design and Synthesis and Center for Cannabis Research, School of Pharmacy, Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelIntragel, Wadi El Haj, Nazareth 17111, IsraelThe Alex Grass Center for Drug Design and Synthesis and Center for Cannabis Research, School of Pharmacy, Institute of Drug Research, The Hebrew University of Jerusalem, Jerusalem 9112001, IsraelPolyanhydrides have been synthesized for decades by melt-polycondensation of diacid monomers and 5 to >10 times mole excess acetic anhydride to diacid monomers to form polymers with a polydispersity ranging from 2.5 to 6 and low reproducibility. Hydrophobic segments in polyanhydrides are beneficial to hinder the characteristic hydrolytic cleavage of an anhydride bond that provides stable polyanhydrides at room temperature. The objective of this work is to synthesize aliphatic polyanhydrides with various hydrophobic segments, controllable and reproducible molecular weight, and low polydispersity that are essential for potential use as drug carriers. A series of polyanhydrides of suberic, azelaic, sebacic, and dodecanedioic acids with controlled molecular weight, reduced polydispersity, and standard deviation of molecular weights, have been synthesized. All synthesized polyanhydrides were thoroughly characterized by NMR, Fourier transform infrared spectroscopy, and gel permeation chromatography. Molecular weights of the synthesized polyanhydrides are highly controllable, depending on the degree of activation of the dicarboxylic acid monomers, i.e., the amount of acetic anhydride used during synthesis. Polyanhydrides have been synthesized in triplicate by melt-polycondensation, using various mole ratios of acetic anhydride to diacids. The standard deviation of the molecular weights of the polyanhydrides is minute when using 1 equivalent of acetic anhydride during the activation of dicarboxylic acids, whereas if excess acetic anhydride is used, the standard deviation is very high. The effect of safe and natural inorganic catalysts, Calcium oxide, Zinc oxide, and Calcium carbonate on polymerization is also studied. As-synthesized poly(sebacic acid) can offer convenience to use in controlled drug delivery applications. In vitro drug release study using Temozolamide (TMZ), a medication used to treat brain tumors such as glioblastoma and anaplastic astrocytoma, shows 14% TMZ release after the first hour and 70% release over one day from the poly(sebacic acid) wafers.https://www.mdpi.com/1999-4923/14/7/1403polyanhydridescontrolled molecular weightmelt polycondensationdrug delivery |
| spellingShingle | Radhakanta Ghosh Yuvaraj Arun Peter Siman Abraham J. Domb Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight Pharmaceutics polyanhydrides controlled molecular weight melt polycondensation drug delivery |
| title | Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight |
| title_full | Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight |
| title_fullStr | Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight |
| title_full_unstemmed | Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight |
| title_short | Synthesis of Aliphatic Polyanhydrides with Controllable and Reproducible Molecular Weight |
| title_sort | synthesis of aliphatic polyanhydrides with controllable and reproducible molecular weight |
| topic | polyanhydrides controlled molecular weight melt polycondensation drug delivery |
| url | https://www.mdpi.com/1999-4923/14/7/1403 |
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