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      HA/HSA co-modified erlotinib–albumin nanoparticles for lung cancer treatment

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          Abstract

          Background

          Aim of this study was to prepare the hyaluronic acid and human serum albumin modified erlotinib nanoparticles (ERT-HSA-HA NPs) delivery system by a precipitation method.

          Methods

          ERT-HSA-HA NPs were characterized for physical properties, such as morphology and particle size, and in vitro drug release. Moreover, the cytotoxicity, cellular uptake, in vivo studies of ERT-HSA-HA nanoparticle were investigated and compared in A549 cells.

          Results

          The ERT-HSA-HA NPs showed spherical morphology, and their hydrodynamic diameter was 112.5±2.8 nm. The drug loading amount and encapsulation efficiency were 5.6% and 81.2%, respectively. After 3 months of storage, no dramatic change, such as visible aggregation, drug content changes, and precipitation, in the appearance of ERT-HSA-HA NPs occurred. In vitro release showed that the release of ERT from HSA-HA NPs was slow, without obvious burst effects at an early stage. In in vivo studies, ERT-HSA-HA NPs showed a superior antiproliferative effect on A549 cells, and the HA modification strategy can also facilitate the high-efficiency uptake of ERT-HSA NPs by A549 cells. Pharmacokinetic studies showed that the form of NPs could significantly extend the role of ERT in vivo (provided higher bioavailability). However, there was no significant difference in the pharmacokinetic parameters between ERT-HSA NPs and ERT-HSA-HA NPs after intravenous administration. In terms of in vivo antitumor activity, ERT-HSA-HA NP-treated mice showed a significantly suppressed tumor growth and no relapse after 30 d of treatment.

          Conclusion

          HA/HSA co-modified erlotinib albumin nanoparticles was expected to be a new strategy in the treatment of lung cancer.

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          Most cited references 26

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          Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.

           Felix Kratz (2008)
          Albumin is playing an increasing role as a drug carrier in the clinical setting. Principally, three drug delivery technologies can be distinguished: coupling of low-molecular weight drugs to exogenous or endogenous albumin, conjugation with bioactive proteins and encapsulation of drugs into albumin nanoparticles. The accumulation of albumin in solid tumors forms the rationale for developing albumin-based drug delivery systems for tumor targeting. Clinically, a methotrexate-albumin conjugate, an albumin-binding prodrug of doxorubicin, i.e. the (6-maleimido)caproylhydrazone derivative of doxorubicin (DOXO-EMCH), and an albumin paclitaxel nanoparticle (Abraxane) have been evaluated clinically. Abraxane has been approved for treating metastatic breast cancer. An alternative strategy is to bind a therapeutic peptide or protein covalently or physically to albumin to enhance its stability and half-life. This approach has been applied to peptides with antinociceptive, antidiabetes, antitumor or antiviral activity: Levemir, a myristic acid derivative of insulin that binds to the fatty acid binding sites of circulating albumin, has been approved for the treatment of diabetes. Furthermore, Albuferon, a fusion protein of albumin and interferon, is currently being assessed in phase III clinical trials for the treatment of hepatitis C and could become an alternative to pegylated interferon. This review gives an account of the different drug delivery systems which make use of albumin as a drug carrier with a focus on those systems that have reached an advanced stage of preclinical evaluation or that have entered clinical trials.
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            Optimization of the preparation process for human serum albumin (HSA) nanoparticles.

            Nanoparticles prepared by desolvation and subsequent crosslinking of human serum albumin (HSA) represent promising carriers for drug delivery. Particle size is a crucial parameter, in particular for the in vivo behaviour of nanoparticles after intravenous injection. The objective of the present study is the development of a desolvation procedure for the preparation of HSA-based nanoparticles under the aspect of a controllable particle size between 100 and 300 nm in combination with a narrow size distribution. A pump-controlled preparation method was established which enabled particle preparation under defined conditions. Several factors of the preparation process, such as the rate of addition of the desolvating agent, the pH value and the ionic composition of the HSA solution, the protein concentration, and the conditions of particle purification were evaluated. The pH value of the HSA solution prior to the desolvation procedure was identified as the major factor determining particle size. Varying this parameter, (mean) particle diameters could be adjusted between 150 and 280 nm, higher pH values leading to smaller nanoparticles. Washing the particles by differential centrifugation led to significantly narrower size distributions. The reproducibility of the particle size and particle size distribution under the proposed preparation conditions was demonstrated by sedimentation velocity analysis in the analytical ultracentrifuge and the cellular uptake of those nanoparticles was studied by confocal microscope imaging and FACS analysis. The stability of the resulting nanoparticles was evaluated by pH and buffer titration experiments. Only pH values distinctly outside the isoelectric pH range of HSA and low salt concentrations were able to prevent nanoparticle agglomeration.
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              Nanocomposite Hydrogels: 3D Polymer-Nanoparticle Synergies for On-Demand Drug Delivery.

              Considerable progress in the synthesis and technology of hydrogels makes these materials attractive structures for designing controlled-release drug delivery systems. In particular, this review highlights the latest advances in nanocomposite hydrogels as drug delivery vehicles. The inclusion/incorporation of nanoparticles in three-dimensional polymeric structures is an innovative means for obtaining multicomponent systems with diverse functionality within a hybrid hydrogel network. Nanoparticle-hydrogel combinations add synergistic benefits to the new 3D structures. Nanogels as carriers for cancer therapy and injectable gels with improved self-healing properties have also been described as new nanocomposite systems.
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                Author and article information

                Journal
                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                1177-8881
                2018
                23 July 2018
                : 12
                : 2285-2292
                Affiliations
                Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China, wentaolidr@ 12345621cn.com
                Author notes
                Correspondence: Wentao Li, Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, 241 Huaihai West Road, Shanghai 200030, China, Tel/fax +86 21 2220 0000, Email wentaolidr@ 12345621cn.com
                Article
                dddt-12-2285
                10.2147/DDDT.S169734
                6061760
                © 2018 Shen and Li. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Original Research

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