Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment
Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin (DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate ca...
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doaj-150cde1935fe4b9b84fbd5a90f2552122020-11-24T20:51:05ZengElsevierAsian Journal of Pharmaceutical Sciences1818-08762017-11-0112650952010.1016/j.ajps.2017.07.005Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatmentKamonrak Cheewatanakornkool0Sathit Niratisai1Somkamol Manchun2Crispin R. Dass3Pornsak Sriamornsak4Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, ThailandDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, ThailandPharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, ThailandSchool of Pharmacy, Faculty of Health Sciences, Curtin University, Perth, WA 6845, AustraliaDepartment of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, ThailandNovel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin (DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical shape. However, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character; in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors.http://www.sciencedirect.com/science/article/pii/S1818087617304750MicrobeadsThiolated pectinDoxorubicinConjugateColorectal cancer |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Kamonrak Cheewatanakornkool Sathit Niratisai Somkamol Manchun Crispin R. Dass Pornsak Sriamornsak |
spellingShingle |
Kamonrak Cheewatanakornkool Sathit Niratisai Somkamol Manchun Crispin R. Dass Pornsak Sriamornsak Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment Asian Journal of Pharmaceutical Sciences Microbeads Thiolated pectin Doxorubicin Conjugate Colorectal cancer |
author_facet |
Kamonrak Cheewatanakornkool Sathit Niratisai Somkamol Manchun Crispin R. Dass Pornsak Sriamornsak |
author_sort |
Kamonrak Cheewatanakornkool |
title |
Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment |
title_short |
Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment |
title_full |
Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment |
title_fullStr |
Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment |
title_full_unstemmed |
Characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment |
title_sort |
characterization and in vitro release studies of oral microbeads containing thiolated pectin–doxorubicin conjugates for colorectal cancer treatment |
publisher |
Elsevier |
series |
Asian Journal of Pharmaceutical Sciences |
issn |
1818-0876 |
publishDate |
2017-11-01 |
description |
Novel oral microbeads were developed based on a biopolymer–drug conjugate of doxorubicin (DOX) conjugated with thiolated pectin via reducible disulfide bonds. The microbeads were fabricated by ionotropic gelation with cations such as Al3+, Ca2+ and Zn2+. The results showed that using zinc acetate can produce the strongest microbeads with spherical shape. However, the microbeads prepared from thiolated pectin–DOX conjugate were very soft and irregular in shape. To produce more spherical microbeads with suitable strength, the native pectin was then added to the formulations. The particle size of the microbeads ranged from 0.87 to 1.14 mm. The morphology of the microbeads was characterized by optical and scanning electron microscopy. DOX was still in crystalline form when used in preparing the microbeads, as confirmed by powder X-ray diffractometry. Drug release profiles showed that the microbeads containing thiolated pectin–DOX conjugate exhibited reduction-responsive character; in reducing environments, the thiolated pectin–DOX conjugate could uncouple resulting from a cleavage of the disulfide linkers and consequently release the DOX. The best-fit release kinetics of the microbeads containing thiolated pectin–DOX conjugate, in the medium without reducing agent, fit the Korsmeyer–Peppas model while those in the medium with reducing agent fit a zero-order release model. These results suggested that the microbeads containing thiolated pectin–DOX conjugate may be a promising platform for cancer-targeted delivery of DOX, exploiting the reducing environment typically found in tumors. |
topic |
Microbeads Thiolated pectin Doxorubicin Conjugate Colorectal cancer |
url |
http://www.sciencedirect.com/science/article/pii/S1818087617304750 |
work_keys_str_mv |
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