Abstract
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®) 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.
Highlights
Doxorubicin (DOX) was first extracted from Streptomyces peucetius var. caesius in the 1970s [1]
The MnCO3 template is dissolved with EDTA and the final DOX-human serum albumin (HSA)-MPs are obtained
The DOX entrapped into protein particles around 25% which is likely due to hydrophilic, hydrophobic contacts and hydrogen bond between DOX and albumin in the MnCO3 template
Summary
Doxorubicin (DOX) was first extracted from Streptomyces peucetius var. caesius in the 1970s [1]. As conventional chemotherapeutic drug DOX exhibits high toxicity due to the limited accessibility of the drug by the tumor cell To avoid these effects, various types of drug carriers have been developed. Pegylated liposomal doxorubicin (Doxil®, Lipodox®) and unpegylated (Myocet®) (FDA-approved) [8], encapsulated dextran–DOX conjugate using chitosan nanoparticles [9], DOX-loaded mesoporous silica nanoparticle [10] and Dox-encapsulated in micelles or nanoemulsion [11] are being investigated as possible candidates. Most of these formulations showed a lower incident of cardiotoxicity and myelosuppression when compared with conventional ones [12]
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