Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies
Doxorubicin cardiotoxicity has led to the development of superior chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils and thrombocytes from AD 198 therapy must be limited. This can be done by the development of a targeted drug delivery system that delivers AD 198 to the...
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-04-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/10/2/50 |
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| author | Nivesh K. Mittal Bivash Mandal Pavan Balabathula Saini Setua Dileep R. Janagam Leonard Lothstein Laura A. Thoma George C. Wood |
| author_facet | Nivesh K. Mittal Bivash Mandal Pavan Balabathula Saini Setua Dileep R. Janagam Leonard Lothstein Laura A. Thoma George C. Wood |
| author_sort | Nivesh K. Mittal |
| collection | DOAJ |
| description | Doxorubicin cardiotoxicity has led to the development of superior chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils and thrombocytes from AD 198 therapy must be limited. This can be done by the development of a targeted drug delivery system that delivers AD 198 to the malignant cells. The current research highlights the development and in vitro analysis of targeted liposomes containing AD 198. The best lipids were identified and optimized for physicochemical effects on the liposomal system. Physiochemical characteristics such as size, ζ-potential, and dissolution were also studied. Active targeting to CD22 positive cells was achieved by conjugating anti-CD22 Fab’ to the liposomal surface. Size and ζ-potential of the liposomes was between 115 and 145 nm, and −8 to−15 mV. 30% drug was released over 72 h. Higher cytotoxicity was observed in CD22+ve Daudi cells compared to CD22−ve Jurkat cells. The route of uptake was a clathrin- and caveolin-independent pathway. Intracellular localization of the liposomes was in the endolysosomes. Upon drug release, apoptotic pathways were activated partly by the regulation of apoptotic and oncoproteins such as caspase-3 and c-myc. It was observed that the CD22 targeted drug delivery system was more potent and specific compared to other untargeted formulations. |
| first_indexed | 2024-04-11T12:16:46Z |
| format | Article |
| id | doaj.art-0fefbc494acf4620ad0fc8703c3d47a3 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-11T12:16:46Z |
| publishDate | 2018-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-0fefbc494acf4620ad0fc8703c3d47a32022-12-22T04:24:15ZengMDPI AGPharmaceutics1999-49232018-04-011025010.3390/pharmaceutics10020050pharmaceutics10020050Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell MalignanciesNivesh K. Mittal0Bivash Mandal1Pavan Balabathula2Saini Setua3Dileep R. Janagam4Leonard Lothstein5Laura A. Thoma6George C. Wood7Plough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, Memphis, TN 38163, USAPlough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, Memphis, TN 38163, USAPlough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USAPlough Center for Sterile Drug Delivery Solutions, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pathalogy, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, Memphis, TN 38163, USADoxorubicin cardiotoxicity has led to the development of superior chemotherapeutic agents such as AD 198. However, depletion of healthy neutrophils and thrombocytes from AD 198 therapy must be limited. This can be done by the development of a targeted drug delivery system that delivers AD 198 to the malignant cells. The current research highlights the development and in vitro analysis of targeted liposomes containing AD 198. The best lipids were identified and optimized for physicochemical effects on the liposomal system. Physiochemical characteristics such as size, ζ-potential, and dissolution were also studied. Active targeting to CD22 positive cells was achieved by conjugating anti-CD22 Fab’ to the liposomal surface. Size and ζ-potential of the liposomes was between 115 and 145 nm, and −8 to−15 mV. 30% drug was released over 72 h. Higher cytotoxicity was observed in CD22+ve Daudi cells compared to CD22−ve Jurkat cells. The route of uptake was a clathrin- and caveolin-independent pathway. Intracellular localization of the liposomes was in the endolysosomes. Upon drug release, apoptotic pathways were activated partly by the regulation of apoptotic and oncoproteins such as caspase-3 and c-myc. It was observed that the CD22 targeted drug delivery system was more potent and specific compared to other untargeted formulations.http://www.mdpi.com/1999-4923/10/2/50AD 198B-cell malignancyliposomenanoparticleCD22 targeting |
| spellingShingle | Nivesh K. Mittal Bivash Mandal Pavan Balabathula Saini Setua Dileep R. Janagam Leonard Lothstein Laura A. Thoma George C. Wood Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies Pharmaceutics AD 198 B-cell malignancy liposome nanoparticle CD22 targeting |
| title | Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies |
| title_full | Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies |
| title_fullStr | Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies |
| title_full_unstemmed | Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies |
| title_short | Formulation, Development, and In Vitro Evaluation of a CD22 Targeted Liposomal System Containing a Non-Cardiotoxic Anthracycline for B Cell Malignancies |
| title_sort | formulation development and in vitro evaluation of a cd22 targeted liposomal system containing a non cardiotoxic anthracycline for b cell malignancies |
| topic | AD 198 B-cell malignancy liposome nanoparticle CD22 targeting |
| url | http://www.mdpi.com/1999-4923/10/2/50 |
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