Clinically applicable haemoglobin-based oxygen carriers (HBOCs) should neither induce immunological nor toxic reactions. Additionally, Hb should be protected against oxidation. In the absence of protective enzymes (superoxide dismutase (SOD) and catalase (CAT)) Hb is oxidized to MetHb and thus losing its function of oxygen delivery. Alternatively, polydopamine (PD), a scavenger of free radicals, could be used for Hb protection against oxidation Therefore, we synthetized HbMPs modified with PD. The content of functional haemoglobin in these PD-HbMPs was twice higher than that in the control HbMPs due to the protective antioxidant effect of PD. In addition, the PD-HbMPs exhibited a high scavenging activity of free radicals including H 2 O 2 and excellent biocompatibility. In contrast to monomeric dopamine, which has been shown to produce toxic effects on neurons due to formation of H 2 O 2 , hydroxyl radicals and superoxide during the process of auto-oxidation, PD-HbMPs are not neurotoxic. Consequently, the results presented here suggest a great potential of PD-HbMPs as HBOCs.
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.
Hemoglobin-based oxygen carriers (HBOCs) represent a propitious type of blood substitute to transport oxygen throughout the body while acting as a carrier in biomedical applications. However, HBOCs in blood are recognized and rapidly scavenged by the body’s innate immune systems. To overcome this problem, HBOCs require a surface modification that provides protection against detection and elimination in order to prolong their circulation time after administration. In this study, we investigated different surface modifications of hemoglobin submicron particles (HbMPs) by double/triple precipitation, as well as by adsorption of human serum albumin (HSA), hyaluronic acid (HA), and pluronic (Plu) to discover how diverse surface modifications influence the oxygen binding capacity and the binding of anti-hemoglobin (Hb) antibodies, immunoglobulin G (IgG), and haptoglobin (HP) to HbMPs. The particle size and zeta potential of the six types of HbMP modifications were analyzed by zeta sizer, confocal laser scanning microscopy, and transmission electron microscopy (TEM), and were compared to the unmodified HbMPs. The results revealed that all surface-modified HbMPs had a submicron size with a negative charge. A slight decrease in the oxygen binding capacity was noticed. The specific binding of anti-Hb antibodies, IgG, and HP to all surface-modified HbMPs was reduced. This indicates a coating design able to protect the particles from detection and elimination processes by the immune system, and should lead to a delayed clearance and the required and essential increase in half-life in circulation of these particles in order to fulfill their purpose. Our surface modification method reflects a promising strategy for submicron particle design, and can lead the way toward novel biomedical applications.
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