Development of hyaluronic acid-Fe2O3 hybrid magnetic nanoparticles for targeted delivery of peptides

Division of Allergy and Immunology, Department of Internal Medicine, College of Medicine, University of South Florida, Tampa, Florida 33612, USA.
Nanomedicine: nanotechnology, biology, and medicine (Impact Factor: 6.16). 07/2007; 3(2):132-7. DOI: 10.1016/j.nano.2007.03.001
Source: PubMed


Novel hybrid nanoparticles comprised of hyaluronic acid (HA) and iron oxide were synthesized and characterized for the first time with the average diameter of less than 160 nm. The iron oxide (Fe2O3) particles are hybridized between HA layers by electrostatic interactions between the positive surface charge of the Fe2O3 nanoparticles and the negative charge of the carboxylate groups of HA, forming a corral-like structure. The particles were also characterized by FTIR and NMR to verify the hybridization. The particles were tested for their ability to deliver peptides to the cells using HEK293 and A549 cells. Results show that these particles delivered peptides at about 100% level. These HA-iron oxide nanoparticles are expected to be useful in developing effective tissue and cell targeting systems.

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    • "c o m / l o c a t e / b b a m e m recruit HA for active targeting. Using this principle, many studies have been performed with HA–drug conjugates [8] [9] [10] or HA-targeted nanoparticles (NP) [11] [12] [13] [14] [15] [16] [17] [18]. Of the various NPs tested, liposome-based NPs are among the best studied and clinically validated [19]. "
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    ABSTRACT: Pancreatic adenocarcinoma is often diagnosed when metastatic events have occurred. The early spread of circulating cancer cells expressing the CD44 receptor may play a crucial role in this process. In this study, we have investigated the cellular delivery ability and both in vitro and in vivo anti-tumoural activity of liposomes conjugated with two different low molecular weight hyaluronic acid (HA 4.8kDa and HA 12kDa), the primary ligand of CD44, and containing a lipophilic gemcitabine (GEM) pro-drug. By confocal microscopy and flow cytometry analyses, we demonstrate that the cellular uptake into a highly CD44-expressing pancreatic adenocarcinoma cell line is higher with HA-conjugated (12kDa>4.8kDa) than non-conjugated liposomes. Consistently, in vitro cytotoxic assays display an increased sensitivity towards GEM containing HA-liposomes, compared to non-conjugated liposomes. Conversely, CD44 non-expressing normal cells show a similar uptake and in vitro cytotoxicity with both HA-conjugated and non-conjugated liposomes. Furthermore, we demonstrate that the HA-liposomes are taken up into the cells via lipid raft-mediated endocytosis. All the liposome formulations containing GEM show a higher antitumoral activity than free GEM in a mouse xenograft tumour model of human pancreatic adenocarcinoma. The 12kDa HA-liposomes have the strongest efficiency, while non-conjugated liposomes and the 4.8kDa HA-liposomes are similarly active. Taken together, our results provide a strong rationale for further development of HA-conjugated liposomes to treat pancreatic adenocarcinoma.
    Biochimica et Biophysica Acta 02/2013; 1828(5). DOI:10.1016/j.bbamem.2013.01.020 · 4.66 Impact Factor
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    • "PEG-coated MNP has the disadvantage such as limited binding sites available for further ligand binding (Gupta & Gupta, 2005), and the coating thickness can significantly affect their relaxivity (Laconte et al., 2007). In addition to PEG coating, other materials such as antibiofouling poly(TMSMA-r-PEGMA) (Lee et al., 2006), hyaluronic acid layers (Kumar et al., 2007) and carboxylfunctionalized poly(amidoamine) dendrimers of generation 3 (Shi et al., 2007) have also been used to coat the surface of IO nanoparticles for either increasing circulation time in the blood or delivering peptides at high efficiency. "

    Smart Nanoparticles Technology, 04/2012; , ISBN: 978-953-51-0500-8
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    • "Furthermore, an experimental study of hyaluronic acid-conjugated butyric acid has showed rapid cellular uptake in a human breast carcinoma cell line.10 Another example of the use of hyaluronic acid, to target cells and tissues delivering peptides, comes from a study using hybrid nanoparticles containing hyaluronic acid and iron oxide which showed high efficiency due to highly specific targeting of CD44, a hyaluronic acid binding receptor found on the surface of tumor cells and inflammatory cells.11 In the field of ocular drug delivery, hyaluronic acid has been used to modify chitosan nanoparticles, indicating that it might enhance their mucoadhesiveness and efficiency.12 "
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    ABSTRACT: Injectable filling agents offer the promise of a better appearance without surgery and, among them, hyaluronic acid is the most commonly used. Although complications are rare, it is necessary to know the possible side effects and complications in order to be prepared for their management. That is why many researchers have been focusing on the interactions between hyaluronic acid and pathogens, inflammatory mediators, the immune system, and markers of oxidative stress to achieve efficient drug delivery, given that hyaluronic acid has widening applications in the field of nanomedicine. Here we report the case of a 37-year-old female patient who returned to our clinic with an abscess in her left cheek 3 months after a deep injection of 1 mL of stabilized hyaluronic acid in both cheeks. Steroid and antibiotic therapy was initiated without success, and abscess drainage was performed. Extraction of tooth 16 was performed 11 days after insertion of drains into the abscess. Laboratory blood tests showed acute inflammation of presumed bacterial etiology. Microbiological examination of pus was negative. Bacterial cultures were found in the extracted tooth. After antibiotic therapy, a complete reversal of the pathological process was observed. The present report highlights the need to assess periodontal problems prior to any aesthetic facial treatment. Analyses of further case reports and clinical studies are necessary to understand the potential role of hyaluronic acid in the formation of biofilm, and how to avoid this complication, thereby increasing the safety of hyaluronic acid-based procedures.
    International Journal of Nanomedicine 03/2012; 7:1441-7. DOI:10.2147/IJN.S27994 · 4.38 Impact Factor
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