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) 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.

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In vitro studies on the interaction between human serum albumin and fosfomycin disodium salt, an antibiotic drug by multi-spectroscopic and molecular docking methods

Molecular Biology Reports ◽

10.1007/s11033-014-3092-y ◽

2014 ◽

Vol 41 (4) ◽

pp. 2377-2387 ◽

Cited By ~ 4

Author(s):

Manjunath D. Meti ◽

Kirthi S. Byadagi ◽

Sharanappa T. Nandibewoor ◽

Shrinivas D. Joshi ◽

Uttam A. More ◽

...

Keyword(s):

Molecular Docking ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Disodium Salt ◽

In Vitro Studies ◽

Antibiotic Drug

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Human Serum Albumin Nanoparticles as a Carrier for On-Demand Sorafenib Delivery

Current Pharmaceutical Biotechnology ◽

10.2174/1389201022666210826152311 ◽

2021 ◽

Vol 22 ◽

Author(s):

Tania Caputo ◽

Angela Maria Cusano ◽

Menotti Ruvo ◽

Anna Aliberti ◽

Andrea Cusano

Keyword(s):

Drug Delivery ◽

Human Serum Albumin ◽

Drug Release ◽

Serum Albumin ◽

Human Serum ◽

Encapsulation Efficiency ◽

Kinase Inhibitor ◽

Force Microscopy ◽

Atomic Force

Background: Drug delivery systems based on Human Serum Albumin (HSA) have been widely investigated due to their capability to interact with several molecules together with their nontoxicity, non-immunogenicity and biocompatibility. Sorafenib (SOR) is a kinase inhibitor used as the first-line treatment in hepatic cancer. However, because of its several intrinsic drawbacks (low solubility and bioavailability), there is a growing need for discovering new carriers able to overcome the current limitations. Objective: To study HSA particles loaded with SOR as a thermal responsive drug delivery system. Method: A detailed spectroscopy analysis of the HSA and SOR interaction in solution was carried out in order to characterize the temperature dependence of the complex. Based on this study, the synthesis of HSA particles loaded with SOR was optimized. Particles were characterized by Dynamic Light Scattering, Atomic Force Microscopy and by spectrofluorometer. Encapsulation efficiency and in vitro drug release were quantified by RP-HPLC. Results: HSA particles were monodispersed in size (≈ 200 nm); encapsulation efficiency ranged from 25% to 58%. Drug release studies that were performed at 37 °C and 50 °C showed that HS5 particles achieved a drug release of 0.430 µM in 72 hours at 50 °C in PBS buffer, accomplishing a 4.6-fold overall SOR release enhancement following a temperature increase from 37 °C to 50 °C. Conclusion: The system herein presented has the potential to exert a therapeutic action (in the nM range) triggering a sustained temperature-controllable release of relevant drugs.

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Preparation, Characterization, and In Vitro Release of Vinorelbine Tartrate (VLBT)- Loaded Folate-conjugated Recombination Human Serum Albumin (rHSA) Nanoparticles with Different Degree of Cross-linking

Current Nanoscience ◽

10.2174/157341312803989042 ◽

2012 ◽

Vol 8 (6) ◽

pp. 885-895

Author(s):

Yuangang Zu ◽

Xue Han ◽

Xiuhua Zhao ◽

Yong Li ◽

Wei Wang ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

In Vitro Release ◽

Cross Linking ◽

Vitro Release

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Human serum albumin nanoparticles as an efficient noscapine drug delivery system for potential use in breast cancer: preparation and in vitro analysis

International Journal of Nanomedicine ◽

10.2147/ijn.s10443 ◽

2010 ◽

pp. 525 ◽

Cited By ~ 18

Author(s):

Satya Satya Prakash

Keyword(s):

Breast Cancer ◽

Drug Delivery ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Albumin Nanoparticles ◽

Vitro Analysis ◽

Potential Use ◽

In Vitro Analysis

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The Therapeutic Effect of Human Serum Albumin Dimer-Doxorubicin Complex against Human Pancreatic Tumors

Pharmaceutics ◽

10.3390/pharmaceutics13081209 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1209

Author(s):

Ryo Kinoshita ◽

Yu Ishima ◽

Victor T. G. Chuang ◽

Hiroshi Watanabe ◽

Taro Shimizu ◽

...

Keyword(s):

Drug Delivery ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Drug Delivery System ◽

Delivery System ◽

Drug Carrier ◽

Antitumor Drug ◽

Pancreatic Tumors

Human serum albumin (HSA) is a versatile drug carrier with active tumor targeting capacity for an antitumor drug delivery system. Nanoparticle albumin-bound (nab)-technology, such as nab-paclitaxel (Abraxane®︎), has attracted significant interest in drug delivery research. Recently, we demonstrated that HSA dimer (HSA-d) possesses a higher tumor distribution than HSA monomer (HSA-m). Therefore, HSA-d is more suitable as a drug carrier for antitumor therapy and can improve nab technology. This study investigated the efficacy of HSA-d-doxorubicin (HSA-d-DOX) as next-generation nab technology for tumor treatment. DOX conjugated to HSA-d via a tunable pH-sensitive linker for the controlled release of DOX. Lyophilization did not affect the particle size of HSA-d-DOX or the release of DOX. HSA-d-DOX showed significantly higher cytotoxicity than HSA-m-DOX in vitro. In the SUIzo Tumor-2 (SUIT2) human pancreatic tumor subcutaneous inoculation model, HSA-d-DOX could significantly inhibit tumor growth without causing serious side effects, as compared to the HSA binding DOX prodrug, which utilized endogenous HSA as a nano-drug delivery system (DDS) carrier. These results indicate that HSA-d could function as a natural solubilizer of insoluble drugs and an active targeting carrier in intractable tumors with low vascular permeability, such as pancreatic tumors. In conclusion, HSA-d can be an effective drug carrier for the antitumor drug delivery system against human pancreatic tumors.

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A Redox-Sensitive Micelle-Like Nanoparticle Self-Assembled from Amphiphilic Adriamycin-Human Serum Albumin Conjugates for Tumor Targeted Therapy

BioMed Research International ◽

10.1155/2015/987404 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Lin Chen ◽

Feng Chen ◽

Mengxin Zhao ◽

Xiandi Zhu ◽

Changhong Ke ◽

...

Keyword(s):

Cancer Therapy ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Disulfide Bond ◽

Imaging System ◽

In Vitro Cytotoxicity ◽

Gastric Cancer Cells

The application of chemotherapeutic drug adriamycin (ADR) in cancer therapy is limited by its side effects like high toxicity and insolubility. Nanomedicine offers new hope for overcoming the shortcomings. But how to increase in vivo stability and to control intracellular drug release is a key issue for nano-based formulations. Herein, the hydrophobic ADR was successfully linked to the biocompatible human serum albumin (HSA) by disulfide bond 3-(2-pyridyldithio) propionyl hydrazide (PDPH), resulting in amphiphilic HSA-ADR. The novel ADR-HSA micellar NPs which were thus assembled exhibited a well-defined stable core shell structure with glutathione (GSH) sensitive linkers. The stable PDPH linkers at extracellular level were broken by GSH at intracellular level with a controlled ADR release profile. The in vitro cytotoxicity against gastric cancer cells (NCI-N87) was obviously enhanced by such redox-sensitive ADR-HSA NPs. Additionally, as observed by IVIS Lumina II Imaging System (Xenogen), the intratumor accumulation of ADR-HSA NPs was much higher than that of HSA/ADR NPs due to its high stability. Consequently, the in vivo tumor inhibition was significantly promoted after intravenous administration to the Balb/c nude mice bearing gastric tumors. These in vitro/vivo results indicated that disulfide-bond-containing ADR-HSA NPs were an effective nanodrug delivery system for cancer therapy.

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