Boron neutron capture therapy (BNCT) represents a promising approach for tumor therapy. A critical requirement for BNCT is tumor targeting, a goal that is currently addressed with the development of ...low and high molecular weight agents capable of interacting with receptors expressed by cancer cells. Here, we describe a new bioconjugate (HApCB) composed by n-propyl carborane linked to hyaluronan (HA) via an ester linkage for a degree of substitution of approximately 30%, leading to a water-soluble derivative. The structure and main physicochemical characteristics of the new HA derivative were determined by means of Fourier transform infrared, fluorescence, and 1H, 13C, and 10B NMR analysis and are herein reported in detail. As HA is recognized by the CD44 antigen, densely populating the surface of many tumor cells, HApCB is expected to deliver boron atoms from the locally released carborane cages directly to target cells for antitumor application in BNCT. In vitro biological experiments showed that HApCB was not toxic for a variety of human tumor cells of different histotypes, specifically interacted with CD44 as the native unconjugated HA, and underwent uptake by tumor cells, leading to accumulation of amounts of boron atoms largely exceeding those required for a successful BNCT approach. Thus, HApCB may be regarded as a promising new BNCT agent for specific targeting of cancer cells overexpressing the CD44 receptor.
Hyaluronan (HA) is among the most important bioactive polymers in mammals, playing a key role in a number of biological functions. In the last decades, it has been increasingly studied as a ...biomaterial for drug delivery systems, thanks to its physico-chemical features and ability to target and enter certain cells. The most important receptor of HA is ‘Cluster of Differentiation 44’ (CD44), a cell surface glycoprotein over-expressed by a number of cancers and heavily involved in HA endocytosis. Moreover, CD44 is highly expressed by keratinocytes, activated macrophages and fibroblasts, all of which can act as ‘reservoirs’ for intracellular pathogens. Interestingly, both CD44 and HA appear to play a key role for the invasion and persistence of such microorganisms within the cells. As such, HA is increasingly recognised as a potential target for nano-carriers development, to pursuit and target intracellular pathogens, acting as a ‘Trojan Horse’. This review describes the biological relationship between HA, CD44 and the entry and survival of a number of pathogens within the cells and the subsequent development of HA-based nano-carriers for enhancing the intracellular activity of antimicrobials.
Hyaluronic acid (HA) is one of the most used biopolymers in the development of drug delivery systems, due to its biocompatibility, biodegradability, non-immunogenicity and intrinsic-targeting ...properties. HA specifically binds to CD44; this property combined to the EPR effect could provide an option for reinforced active tumor targeting by nanocarriers, improving drug uptake by the cancer cells via the HA-CD44 receptor-mediated endocytosis pathway. Moreover, HA can be easily chemically modified to tailor its physico-chemical properties in view of specific applications. The derivatization with cholesterol confers to HA an amphiphilic character, and then the ability of anchoring to niosomes. HA-Chol was then used to coat Span® or Tween® niosomes providing them with an intrinsic targeting shell. The nanocarrier physico-chemical properties were analyzed in terms of hydrodynamic diameter, ζ-potential, and bilayer structural features to evaluate the difference between naked and HA-coated niosomes. Niosomes stability was evaluated over time and in bovine serum. Moreover, interaction properties of HA-coated nanovesicles with model membranes, namely liposomes, were studied, to obtain insights on their interaction behavior with biological membranes in future experiments. The obtained coated systems showed good chemical physical features and represent a good opportunity to carry out active targeting strategies.
Scleroglucan (Sclg) and guar gum (GG) are capable of giving gels in the presence of borax. This study focuses on how a mixed system of the two polysaccharides can be affected by the addition of ...borax. The anisotropic swelling behavior of tablets obtained by compression of the freeze-dried new gel system is also investigated and compared to that of Sclg and GG alone. Rheological characterization evidences a synergistic effect in terms of critical time, mesh size, as well as crosslinking density. Also creep recovery experiments, carried out in the presence of borax, show a synergistic effect: when the polymers are mixed, quite low compliance was estimated in comparison to that of Sclg and GG. On the other side, the flexible chains of GG induce the self-healing properties of the mixed gel system since the rigid, triple helix of Sclg does not show such peculiar characteristics. The deep insight into the physico-chemical properties of the new hydrogel system can play a fundamental role in optimizing its practical application (e.g., in drug delivery, cosmetic products, human tissue repair, wound dressing, and food staff).
Natural antioxidants, such as astaxanthin (AX), resveratrol (RV) and curcumin (CU), are bioactive molecules that show a number of therapeutic effects. However, their applications are remarkably ...limited by their poor water solubility, physico-chemical instability and low bioavailability. In the present work, it is shown that self-assembled hyaluronan (HA)-based nanohydrogels (NHs) are taken up by endothelial cells (Human Umbilical Vein Endothelial Cells, HUVECs), preferentially accumulating in the perinuclear area of oxidatively stressed HUVECs, as evidenced by flow cytometry and confocal microscopy analyses. Furthermore, NHs are able to physically entrap and to significantly enhance the apparent water solubility of AX, RV and CU in aqueous media. AX/NHs, RV/NHs and CU/NHs systems showed good hydrodynamic diameters (287, 214 and 267 nm, respectively), suitable ζ-potential values (−45, −43 and −37 mV, respectively) and the capability to neutralise reactive oxygen species (ROS) in tube. AX/NHs system was also able to neutralise ROS in vitro and did not show any toxicity against HUVECs. This research suggests that HA-based NHs can represent a kind of nano-carrier suitable for the intracellular delivery of antioxidant agents, for the treatment of oxidative stress in endothelial cells.
Nanocarriers have been extensively developed in the biomedical field to enhance the treatment of various diseases. However, to effectively deliver therapeutic agents to desired target tissues and ...enhance their pharmacological activity, these nanocarriers must overcome biological barriers, such as mucus gel, skin, cornea, and blood-brain barriers. Polysaccharides possess qualities such as excellent biocompatibility, biodegradability, unique biological properties, and good accessibility, making them ideal materials for constructing drug delivery carriers. Nanogels, as a novel drug delivery platform, consist of three-dimensional polymer networks at the nanoscale, offering a promising strategy for encapsulating different pharmaceutical agents, prolonging retention time, and enhancing penetration. These attractive properties offer great potential for the utilization of polysaccharide-based nanogels as drug delivery systems to overcome biological barriers. Hence, this review discusses the properties of various barriers and the associated constraints, followed by summarizing the most recent development of polysaccharide-based nanogels in drug delivery to overcome biological barriers. It is expected to provide inspiration and motivation for better design and development of polysaccharide-based drug delivery systems to enhance bioavailability and efficacy while minimizing side effects.
Scleroglucan is a natural polysaccharide that has been proposed for various applications. However there is no investigation on its property variations when the molecular weight of this polymer is ...reduced. Scleroglucan was sonicated at two different polymer concentrations for different periods of time and the effect of sonication was investigated with respect to molecular weight variations and rheological properties. Molar mass, estimated by viscometric measurements, was drastically reduced already after a sonication for a few min. Sonicated samples were used for the preparation of gels in the presence of borate ions. The effect of borax on the new samples was investigated by recording the mechanical spectra and the flow curves. A comparison with the system prepared with the dialysed polymer was also carried out. The anisotropic elongation, observed with tablets of scleroglucan and borax, was remarkably reduced when the sonicated samples were used for the preparation of the gels.
An alternative anticancer therapy based on the use of bovine serum amine oxidase (BSAO), an enzyme that converts polyamines over‐expressed in malignant cells, into hydrogen peroxide and aldehyde(s), ...thus inducing high cytotoxicity in cancer cells, was recently proposed. With the aim of improving the system efficacy by exploiting a nanotechnology approach, BSAO is covalently immobilized onto injectable nanohydrogels (NHs) based on cholesterol‐graft‐hyaluronic acid (HA‐CH), a biocompatible conjugate that spontaneously leads to self‐assembled structures in aqueous solutions. In this study, the physicochemical properties of the HA‐CH‐based NHs and the NHs cytocompatibility are reported. The properties of the NHs‐BSAO system are also studied in terms of protein residual activity, both in vitro and on a model melanoma cell line.
Self‐assembling nanohydrogels based on cholesterol‐graft‐hyaluronic acid represent a good tool for the delivery of therapeutic proteins covalently immobilized by carbodiimide chemistry. Bovine serum amine oxidase, an enzyme that is able to produce antincancer species in situ, is successfully linked on nanohydrogels and tested in vitro on a model melanoma cell line.
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