Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment
SN38 (7-ethyl-10-hydroxy-comptothecin) is a potent metabolite of irinotecan, which has been approved for treatment of metastatic colorectal cancer. Considering the notable potency of SN38, it has been introduced as an anticancer candidate. In this study, human serum albumin (HSA) conjugates of SN38...
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doaj-fa46016cf60e439da26557f9f08d75642020-11-24T22:58:02ZengHindawi LimitedBioMed Research International2314-61332314-61412014-01-01201410.1155/2014/963507963507Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer TreatmentNima Sepehri0Hasti Rouhani1Ahmad Reza Ghanbarpour2Mehdi Gharghabi3Faranak Tavassolian4Mohsen Amini5Seyed Nasser Ostad6Mohammad Hossein Ghahremani7Rassoul Dinarvand8Department of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, IranDepartment of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, IranDepartment of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, IranDepartment of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, IranDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Toxicology-Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, IranDepartment of Pharmaceutics, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, IranSN38 (7-ethyl-10-hydroxy-comptothecin) is a potent metabolite of irinotecan, which has been approved for treatment of metastatic colorectal cancer. Considering the notable potency of SN38, it has been introduced as an anticancer candidate. In this study, human serum albumin (HSA) conjugates of SN38 were formulated to overcome the solubility problem beside improving the active form stability and tumor tissue targeting. In this target, two different molar ratios of conjugates (SN38 : HSA 15 : 1 and 60 : 1) were prepared by derivatization of 20-hydroxyl group of SN38 with glycine, followed by addition of succinyl group to glycine through which HSA was covalently attached. The conjugates with particle size of about 100 nm revealed enhanced water solubility and were relatively stable in neutral and acidic solutions. For SN38-HSA-15 and SN38-HSA-60 IC50 values were compared with irinotecan in HT-29 human colon cancer cells. Furthermore, biodistribution studies of SN38-HSA conjugate resulted in proper blood concentration level within 4 h. Moreover, blood cytotoxicity assay revealed no toxicity effect on liver and spleen. Collectively, our present investigation offers a water-soluble form of SN38 attached to HSA and suggests using favorable properties as a promising anticancer agent for further preclinical and clinical investigations.http://dx.doi.org/10.1155/2014/963507 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nima Sepehri Hasti Rouhani Ahmad Reza Ghanbarpour Mehdi Gharghabi Faranak Tavassolian Mohsen Amini Seyed Nasser Ostad Mohammad Hossein Ghahremani Rassoul Dinarvand |
spellingShingle |
Nima Sepehri Hasti Rouhani Ahmad Reza Ghanbarpour Mehdi Gharghabi Faranak Tavassolian Mohsen Amini Seyed Nasser Ostad Mohammad Hossein Ghahremani Rassoul Dinarvand Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment BioMed Research International |
author_facet |
Nima Sepehri Hasti Rouhani Ahmad Reza Ghanbarpour Mehdi Gharghabi Faranak Tavassolian Mohsen Amini Seyed Nasser Ostad Mohammad Hossein Ghahremani Rassoul Dinarvand |
author_sort |
Nima Sepehri |
title |
Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment |
title_short |
Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment |
title_full |
Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment |
title_fullStr |
Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment |
title_full_unstemmed |
Human Serum Albumin Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN38) for Cancer Treatment |
title_sort |
human serum albumin conjugates of 7-ethyl-10-hydroxycamptothecin (sn38) for cancer treatment |
publisher |
Hindawi Limited |
series |
BioMed Research International |
issn |
2314-6133 2314-6141 |
publishDate |
2014-01-01 |
description |
SN38 (7-ethyl-10-hydroxy-comptothecin) is a potent metabolite of irinotecan, which has been approved for treatment of metastatic colorectal cancer. Considering the notable potency of SN38, it has been introduced as an anticancer candidate. In this study, human serum albumin (HSA) conjugates of SN38 were formulated to overcome the solubility problem beside improving the active form stability and tumor tissue targeting. In this target, two different molar ratios of conjugates (SN38 : HSA 15 : 1 and 60 : 1) were prepared by derivatization of 20-hydroxyl group of SN38 with glycine, followed by addition of succinyl group to glycine through which HSA was covalently attached. The conjugates with particle size of about 100 nm revealed enhanced water solubility and were relatively stable in neutral and acidic solutions. For SN38-HSA-15 and SN38-HSA-60 IC50 values were compared with irinotecan in HT-29 human colon cancer cells. Furthermore, biodistribution studies of SN38-HSA conjugate resulted in proper blood concentration level within 4 h. Moreover, blood cytotoxicity assay revealed no toxicity effect on liver and spleen. Collectively, our present investigation offers a water-soluble form of SN38 attached to HSA and suggests using favorable properties as a promising anticancer agent for further preclinical and clinical investigations. |
url |
http://dx.doi.org/10.1155/2014/963507 |
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