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

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.

Fabrication and Characterization of Human Serum Albumin Particles Loaded with Non-Sericin Extract Obtained from Silk Cocoon as a Carrier System for Hydrophobic Substances

“…In this study, the adsorption of NS to HSA-MnCO 3 particle varied and depended on the concentration and fabrication steps. These results indicated that non-sericin substance with poor water solubility can be entrapped into the HSA-MnCO 3 particle via electrostatic and hydrophobic interactions which is similar to the results of doxorubicin loaded HSA-MnCO 3 particle [16]. The HSA-MnCO 3 templates were incubated with different concentrations of NS.…”

“…This could be suggestive of a common uptake mechanism of the albumin receptor. Similarly, a study involving doxorubicin revealed that it was loaded into HSA-MPs, uptaken by the A549 cells and then localized in the cell lysosomal compartment [ 16 ].…”

“…These HSA particles also display nontoxic and nonimmunogenic properties [ 13 , 14 ]. Additionally, albumin-based micelle nanoparticles have been reported to serve as effective carriers for hydrophobic drugs such as doxorubicin [ 15 , 16 ]. Further, HSA-based nanoparticles have been exploited for their potential as beneficial products in various diagnoses and prescribed therapies, such as Levemir ® and Victoza ® in the treatment of diabetes, Abraxane ® for treating solid tumors, and 99m Tc-aggregated albumin for diagnostic use in nuclear medicine [ 13 ].…”

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…Albumin represents an appealing protein-based macromolecular carrier due to its non-toxicity, non-immunogenicity, biocompatibility, easy incorporation of various drugs, and ability to bind with proteins [21,82,83]. Albumin nanoparticles have been shown to exhibit enhanced affinity for anti-cancer drugs, including paclitaxel [84][85][86][87] (FDAapproved nanoformulation as Abraxane ® /ABI-007 (Celgene) [88]), doxorubicin [87,[89][90][91][92], docetaxel [93][94][95][96], tacrolimus [87,97], and curcumin [98,99].…”

“…Specifically, stimuliresponsive delivery systems have been created to target the acidic pH and/or hypoxic environment characteristic of tumor cells [210] (Figure 5). In this respect, polymeric nanoparticles have been investigated as carriers towards various tumor cells, including breast [44,[211][212][213], colon [91,[214][215][216][217], gastric [169,[218][219][220], liver [116,221,222], bladder [46,223], skin [224,225], lung [36,92,226], prostate [94,[227][228][229], and ovarian [230][231][232] cancer cells (Table 2). In this respect, polymeric nanoparticles have been investigated as carriers towards various tumor cells, including breast [44,[211][212][213], colon [91,[214][215][216][217], gastric [169,[218]…”