2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes
2-O-Acyl-3-O-(1-acyloxyalkyl) prodrug derivatives, 15, of 5,6-isopropylidene-l-ascorbic acid, VCA, and l-ascorbic acid, VC, have been characterized by measuring (1) their solubilities in water (SAQ) and in 1-octanol (SOCT); (2) the ability of one member of the homologous series, 15a, to diffuse thro...
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| Format: | Article |
| Language: | English |
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MDPI AG
2016-07-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/8/3/22 |
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| author | Nikki A. Thiele Jennifer McGowan Kenneth B. Sloan |
| author_facet | Nikki A. Thiele Jennifer McGowan Kenneth B. Sloan |
| author_sort | Nikki A. Thiele |
| collection | DOAJ |
| description | 2-O-Acyl-3-O-(1-acyloxyalkyl) prodrug derivatives, 15, of 5,6-isopropylidene-l-ascorbic acid, VCA, and l-ascorbic acid, VC, have been characterized by measuring (1) their solubilities in water (SAQ) and in 1-octanol (SOCT); (2) the ability of one member of the homologous series, 15a, to diffuse through a silicone membrane from its application in propylene glycol:water (PG:AQ), 30:70; (3) the ability of another member of the series, 15e, to express cellular antioxidant activity (CAA) in HaCaT cells; and (4) the ability of 15e to support cell viability in HaCaT cells. All of the prodrugs were more soluble in 1-octanol than VC or VCA were. 15a, which exhibited a good balance between SOCT and SAQ, was found to deliver approximately 15 times more 15a than VCA delivered VCA through a silicone membrane from PG:AQ, 30:70. Under those conditions, no VC permeated the membrane. 15e, which hydrolyzed to release acetaldehyde as a byproduct instead of the toxin formaldehyde, exhibited approximately 30 times the antioxidant activity of VC in CaHaT cells and supported cell viability up to 900 μM in HaCaT cells. |
| first_indexed | 2024-04-13T09:21:41Z |
| format | Article |
| id | doaj.art-f1c9b1f51c264e22989ac57664e48096 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T09:21:41Z |
| publishDate | 2016-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-f1c9b1f51c264e22989ac57664e480962022-12-22T02:52:36ZengMDPI AGPharmaceutics1999-49232016-07-01832210.3390/pharmaceutics8030022pharmaceutics80300222-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone MembranesNikki A. Thiele0Jennifer McGowan1Kenneth B. Sloan2Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USADepartment of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USADepartment of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA2-O-Acyl-3-O-(1-acyloxyalkyl) prodrug derivatives, 15, of 5,6-isopropylidene-l-ascorbic acid, VCA, and l-ascorbic acid, VC, have been characterized by measuring (1) their solubilities in water (SAQ) and in 1-octanol (SOCT); (2) the ability of one member of the homologous series, 15a, to diffuse through a silicone membrane from its application in propylene glycol:water (PG:AQ), 30:70; (3) the ability of another member of the series, 15e, to express cellular antioxidant activity (CAA) in HaCaT cells; and (4) the ability of 15e to support cell viability in HaCaT cells. All of the prodrugs were more soluble in 1-octanol than VC or VCA were. 15a, which exhibited a good balance between SOCT and SAQ, was found to deliver approximately 15 times more 15a than VCA delivered VCA through a silicone membrane from PG:AQ, 30:70. Under those conditions, no VC permeated the membrane. 15e, which hydrolyzed to release acetaldehyde as a byproduct instead of the toxin formaldehyde, exhibited approximately 30 times the antioxidant activity of VC in CaHaT cells and supported cell viability up to 900 μM in HaCaT cells.http://www.mdpi.com/1999-4923/8/3/22vitamin C">l-ascorbic acidprodrugstopical deliverysolubilitiescellular antioxidant activitycytotoxicitysoft alkyl |
| spellingShingle | Nikki A. Thiele Jennifer McGowan Kenneth B. Sloan 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes Pharmaceutics vitamin C ">l-ascorbic acid prodrugs topical delivery solubilities cellular antioxidant activity cytotoxicity soft alkyl |
| title | 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes |
| title_full | 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes |
| title_fullStr | 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes |
| title_full_unstemmed | 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes |
| title_short | 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes |
| title_sort | 2 o acyl 3 o 1 acyloxyalkyl prodrugs of 5 6 isopropylidene l ascorbic acid and l ascorbic acid antioxidant activity and ability to permeate silicone membranes |
| topic | vitamin C ">l-ascorbic acid prodrugs topical delivery solubilities cellular antioxidant activity cytotoxicity soft alkyl |
| url | http://www.mdpi.com/1999-4923/8/3/22 |
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