Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake

Doxorubicin (DOX) is an effective anthracycline antibiotic drug which is commonly used in a broad range cancer therapy. However, due to dose depending side effects and toxicity to non-cancerous tissues, its clinical applications are restricted. To overcome these limitations, human serum albumin (HSA...

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Main Authors: Saranya Chaiwaree, Ausanai Prapan, Nittiya Suwannasom, Tomás Laporte, Tanja Neumann, Axel Pruß, Radostina Georgieva, Hans Bäumler
Format: Article
Language:English
Published: MDPI AG 2020-03-01
Series:Pharmaceutics
Subjects:
Online Access:https://www.mdpi.com/1999-4923/12/3/224
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author Saranya Chaiwaree
Ausanai Prapan
Nittiya Suwannasom
Tomás Laporte
Tanja Neumann
Axel Pruß
Radostina Georgieva
Hans Bäumler
author_facet Saranya Chaiwaree
Ausanai Prapan
Nittiya Suwannasom
Tomás Laporte
Tanja Neumann
Axel Pruß
Radostina Georgieva
Hans Bäumler
author_sort Saranya Chaiwaree
collection DOAJ
description Doxorubicin (DOX) is an effective anthracycline antibiotic drug which is commonly used in a broad range cancer therapy. However, due to dose depending side effects and toxicity to non-cancerous tissues, its clinical applications are restricted. To overcome these limitations, human serum albumin (HSA) has been investigated as a biocompatible drug delivery vehicle. In this study, human serum albumin submicron particles (HSA-MPs) were fabricated by using the Co-precipitation–Crosslinking–Dissolution technique (CCD technique) and DOX was loaded into the protein particles by absorption. DOX-HSA-MPs showed uniform peanut-like shape, submicron size and negative zeta-potential (−13 mV). The DOX entrapment efficiency was 25% of the initial amount. The in vitro release in phosphate buffered saline pH 7.4 was less than 1% within 5 h. In contrast, up to 40% of the entrapped DOX was released in presence of a protein digesting enzyme mixture (Pronase<sup>®</sup>) within the same time. In addition, in vitro cytotoxicity and cellular uptake of DOX-HSA-MPs were evaluated using the lung carcinoma cell line A549. The results demonstrated that DOX-HSA-MPs reduced the cell metabolic activities after 72 h. Interestingly, DOX-HSA-MPs were taken up by A549 cells up to 98% and localized in the cell lysosomal compartment. This study suggests that DOX-HSA-MPs which was fabricated by CCD technique is seen as a promising biopolymer particle as well as a viable alternative for drug delivery application to use for cancer therapy.
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spelling doaj.art-7cecbc9c9d3c4567adcbf503c17351b42022-12-22T04:23:28ZengMDPI AGPharmaceutics1999-49232020-03-0112322410.3390/pharmaceutics12030224pharmaceutics12030224Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular UptakeSaranya Chaiwaree0Ausanai Prapan1Nittiya Suwannasom2Tomás Laporte3Tanja Neumann4Axel Pruß5Radostina Georgieva6Hans Bäumler7Institute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyJPK BioAFM Business, Nano Surfaces Division, Bruker Nano GmbH, 12489 Berlin, GermanyInstitute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyInstitute of Transfusion Medicine, Charité-Universitätsmedizin Berlin, 10117 Berlin, GermanyDoxorubicin (DOX) is an effective anthracycline antibiotic drug which is commonly used in a broad range cancer therapy. However, due to dose depending side effects and toxicity to non-cancerous tissues, its clinical applications are restricted. To overcome these limitations, human serum albumin (HSA) has been investigated as a biocompatible drug delivery vehicle. In this study, human serum albumin submicron particles (HSA-MPs) were fabricated by using the Co-precipitation–Crosslinking–Dissolution technique (CCD technique) and DOX was loaded into the protein particles by absorption. DOX-HSA-MPs showed uniform peanut-like shape, submicron size and negative zeta-potential (−13 mV). The DOX entrapment efficiency was 25% of the initial amount. The in vitro release in phosphate buffered saline pH 7.4 was less than 1% within 5 h. In contrast, up to 40% of the entrapped DOX was released in presence of a protein digesting enzyme mixture (Pronase<sup>®</sup>) within the same time. In addition, in vitro cytotoxicity and cellular uptake of DOX-HSA-MPs were evaluated using the lung carcinoma cell line A549. The results demonstrated that DOX-HSA-MPs reduced the cell metabolic activities after 72 h. Interestingly, DOX-HSA-MPs were taken up by A549 cells up to 98% and localized in the cell lysosomal compartment. This study suggests that DOX-HSA-MPs which was fabricated by CCD technique is seen as a promising biopolymer particle as well as a viable alternative for drug delivery application to use for cancer therapy.https://www.mdpi.com/1999-4923/12/3/224doxorubicinalbumin particlesccd techniquecellular uptakesubmicron particles
spellingShingle Saranya Chaiwaree
Ausanai Prapan
Nittiya Suwannasom
Tomás Laporte
Tanja Neumann
Axel Pruß
Radostina Georgieva
Hans Bäumler
Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake
Pharmaceutics
doxorubicin
albumin particles
ccd technique
cellular uptake
submicron particles
title Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake
title_full Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake
title_fullStr Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake
title_full_unstemmed Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake
title_short Doxorubicin–Loaded Human Serum Albumin Submicron Particles: Preparation, Characterization and In Vitro Cellular Uptake
title_sort doxorubicin loaded human serum albumin submicron particles preparation characterization and in vitro cellular uptake
topic doxorubicin
albumin particles
ccd technique
cellular uptake
submicron particles
url https://www.mdpi.com/1999-4923/12/3/224
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