Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity
Betulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-02-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fchem.2019.00092/full |
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| author | Mirela Nicolov Roxana M. Ghiulai Mirela Voicu Marius Mioc Adina Octavia Duse Roxana Roman Rita Ambrus Istvan Zupko Elena Alina Moaca Dorina E. Coricovac Claudia Farcas Roxana Marcela Racoviceanu Corina Danciu Cristina-Adriana Dehelean Codruta Soica |
| author_facet | Mirela Nicolov Roxana M. Ghiulai Mirela Voicu Marius Mioc Adina Octavia Duse Roxana Roman Rita Ambrus Istvan Zupko Elena Alina Moaca Dorina E. Coricovac Claudia Farcas Roxana Marcela Racoviceanu Corina Danciu Cristina-Adriana Dehelean Codruta Soica |
| author_sort | Mirela Nicolov |
| collection | DOAJ |
| description | Betulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome these drawbacks, numerous strategies were conducted to improve its physicochemical and pharmacokinetic profile, among which cocrystalization emerged as a promising approach. Thus, our work consisted in obtaining slowly grown cocrystals of BA and ascorbic acid (BA+VitC) in isopropyl alcohol obtained in a hydrothermal experiment. The newly formed cocrystals were characterized by physico-chemical methods such asSEM, DSC, XRPD, and FT-IR spectroscopy demonstrating BA+VitC cocrystal formation while their antioxidant activity revealed an additive antioxidant effect. To investigate the biological effect, BA+VitC cocrystals were tested on HaCat (immortalized human keratinocytes), B164A5 and B16F0 (murine melanoma), MCF7 and MDA-MB-231 (human breast cancer), and HeLa (cervical cancer) cell lines. Results of BA upon the tested tumor cell lines, after co-crystallization with vitamin C, indicated a superior cytotoxic effect with the preservation of a good selectivity index assumably due to an improved BA water solubility and consequently an optimized bioavailability. |
| first_indexed | 2024-04-14T03:00:44Z |
| format | Article |
| id | doaj.art-d56cf8c6e85e45c2a9cc26eead2d6cab |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-14T03:00:44Z |
| publishDate | 2019-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-d56cf8c6e85e45c2a9cc26eead2d6cab2022-12-22T02:15:56ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462019-02-01710.3389/fchem.2019.00092435425Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative ActivityMirela Nicolov0Roxana M. Ghiulai1Mirela Voicu2Marius Mioc3Adina Octavia Duse4Roxana Roman5Rita Ambrus6Istvan Zupko7Elena Alina Moaca8Dorina E. Coricovac9Claudia Farcas10Roxana Marcela Racoviceanu11Corina Danciu12Cristina-Adriana Dehelean13Codruta Soica14Faculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Medicine, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Physics, West University of Timisoara, Timisoara, RomaniaInstitute of Pharmaceutical Technology and Regulatory Affairs, University of Szeged, Szeged, HungaryDepartment of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, HungaryFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaFaculty of Pharmacy, Victor Babes University of Medicine and Pharmacy, Timisoara, RomaniaBetulinic acid (BA) was demonstrated to be a very promising anticancer agent against various tumor cell lines such as breast, colon, lung, and brain. Despite its strong cytotoxic effect, betulinic acid exhibits low water solubility, feature that is reflected in its poor bioavailability. To overcome these drawbacks, numerous strategies were conducted to improve its physicochemical and pharmacokinetic profile, among which cocrystalization emerged as a promising approach. Thus, our work consisted in obtaining slowly grown cocrystals of BA and ascorbic acid (BA+VitC) in isopropyl alcohol obtained in a hydrothermal experiment. The newly formed cocrystals were characterized by physico-chemical methods such asSEM, DSC, XRPD, and FT-IR spectroscopy demonstrating BA+VitC cocrystal formation while their antioxidant activity revealed an additive antioxidant effect. To investigate the biological effect, BA+VitC cocrystals were tested on HaCat (immortalized human keratinocytes), B164A5 and B16F0 (murine melanoma), MCF7 and MDA-MB-231 (human breast cancer), and HeLa (cervical cancer) cell lines. Results of BA upon the tested tumor cell lines, after co-crystallization with vitamin C, indicated a superior cytotoxic effect with the preservation of a good selectivity index assumably due to an improved BA water solubility and consequently an optimized bioavailability.https://www.frontiersin.org/article/10.3389/fchem.2019.00092/fullcocrystalbetulinic acidvitamin Cantioxidant activityantiproliferative activity |
| spellingShingle | Mirela Nicolov Roxana M. Ghiulai Mirela Voicu Marius Mioc Adina Octavia Duse Roxana Roman Rita Ambrus Istvan Zupko Elena Alina Moaca Dorina E. Coricovac Claudia Farcas Roxana Marcela Racoviceanu Corina Danciu Cristina-Adriana Dehelean Codruta Soica Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity Frontiers in Chemistry cocrystal betulinic acid vitamin C antioxidant activity antiproliferative activity |
| title | Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity |
| title_full | Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity |
| title_fullStr | Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity |
| title_full_unstemmed | Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity |
| title_short | Cocrystal Formation of Betulinic Acid and Ascorbic Acid: Synthesis, Physico-Chemical Assessment, Antioxidant, and Antiproliferative Activity |
| title_sort | cocrystal formation of betulinic acid and ascorbic acid synthesis physico chemical assessment antioxidant and antiproliferative activity |
| topic | cocrystal betulinic acid vitamin C antioxidant activity antiproliferative activity |
| url | https://www.frontiersin.org/article/10.3389/fchem.2019.00092/full |
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