Molecularly Imprinted Polymers (PIMs) in Biomedical Applications

Non

Synthesis of sericin-based conjugates by click chemistry: enhancement of sunitinib bioavailability and cell membrane permeation

Sericin is a natural protein that has been used in biomedical and pharmaceutical fields as raw material for polypeptide-based drug delivery systems (DDSs). In this paper, it has been employed as pharmaceutical biopolymer for the production of sunitinib–polypeptide conjugate. The synthesis has been carried out by simple click reaction in water, using the redox couple l-ascorbic acid/hydrogen peroxide as a free radical grafting initiator. The bioconjugate molecular weight (50 kDa < Mw < 75 kDa) was obtained by SDS-PAGE, while the spectroscopic characteristics have been studied in order to reveal the presence of grafted sunitinib. In both FT-IR and UV/Vis spectra, signals corresponding to sunitinib functional groups have been identified. Since sunitinib is an anticancer drug characterized by low bioavailability and low permeability, the bioconjugation aimed at their enhancement. In vitro studies demonstrated that bioavailability has been increased to almost 74%, compared with commercial formulation. Also cell membrane permeability has been augmented in in vitro tests, in which membrane models have been used to determine the lipid membrane/physiological fluid partition coefficient (Kp). The log(Kp) value of the bioconjugate was increased to over 4. This effect resulted in a three-fold decrease of IC50 value against MCF-7 cells

Synthesis and evaluation of wound healing properties of hydro-diab hydrogel loaded with green-synthetized AGNPS: in vitro and in ex vivo studies

In diabetic patients, the presence of neuropathy, peripheral vascular diseases and ischemia, leads to the formation of foot ulcerations with a higher risk of infection because the normal response to bacterial infection is missing. In the aim to control and treat diabetic foot ulcerations (DFUs), wound dressings that are able to absorb exudate, to prevent infections, and to promote wound healing are needed. For this reason, the aim of the present research was to synthetize a biocompatible hydrogel (called HyDrO-DiAb) composed of carboxymethylcellulose loaded with silver nanoparticles (AgNPs) for the treatment of diabetic foot ulcers. In this study, AgNPs were obtained by a green synthesis and, then, were dissolved in a CMC hydrogel that, after a freeze drying process, becomes a flexible and porous structure. The in vitro and in ex vivo wound healing activity of the obtained HyDrO-DiAb hydrogel was evaluatedPeer ReviewedPostprint (published version

Controlled Release of 5-FU from Chi–DHA Nanoparticles Synthetized with Ionic Gelation Technique: Evaluation of Release Profile Kinetics and Cytotoxicity Effect

The ionic gelation technique allows us to obtain nanoparticles able to function as carriers for hydrophobic anticancer drugs, such as 5-fluoruracil (5-FU). In this study, reticulated chitosan– docosahexaenoic acid (Chi–DHAr) nanoparticles were synthesized by using a chemical reaction between amine groups of chitosan (Chi) and carboxylic acids of docosahexaenoic acid (DHA) and the presence of a link between Chi and DHA was confirmed by FT-IR, while the size and morphology of the obtained Chi-DHAr nanoparticles was evaluated with dynamic light scattering (DLS) and scanning electron microscopy (SEM), respectively. Drug-loading content (DLC) and drug-loading efficiency (DLE) of 5-FU in Chi-DHAr nanoparticles were 33.74 ± 0.19% and 7.9 ± 0.26%, respectively, while in the non-functionalized nanoparticles (Chir + 5FU), DLC, and DLE were in the ranges of 23.73 ± 0.14%, 5.62%, and 0.23%, respectively. The in vitro release profile, performed in phosphate buffer saline (PBS, pH 7.4) at 37 °C, indicated that the synthetized Chi–DHAr nanoparticles provided a sustained release of 5-FU. Based on the obtained regression coefficient value (R2), the first order kinetic model provided the best fit for both Chir and Chi-DHAr nanoparticles. Finally, cytotoxicity studies of chitosan, 5-FU, Chir, Chir + 5-FU, Chi-DHAr, and Chi-DHAr + 5-FU nanoparticles were conducted. Overall, Chi-DHAr nanoparticles proved to be much more biocompatible than Chir nanoparticles while retaining the ability to release the drug with high efficiency, especially towards specific types of cancerous cells

A Phenylacetamide Resveratrol Derivative Exerts Inhibitory Effects on Breast Cancer Cell Growth

Resveratrol (RSV) is a natural compound that displays several pharmacological properties, including anti-cancer actions. However, its clinical application is limited because of its low solubility and bioavailability. Here, the antiproliferative and anti-inflammatory activity of a series of phenylacetamide RSV derivatives has been evaluated in several cancer cell lines. These derivatives contain a monosubstituted aromatic ring that could mimic the RSV phenolic nucleus and a longer flexible chain that could confer a better stability and bioavailability than RSV. Using MTT assay, we demonstrated that most derivatives exerted antiproliferative effects in almost all of the cancer cell lines tested. Among them, derivative 2, that showed greater bioavailability than RSV, was the most active, particularly against estrogen receptor positive (ER+) MCF7 and estrogen receptor negative (ER-) MDA-MB231 breast cancer cell lines. Moreover, we demonstrated that these derivatives, particularly derivative 2, were able to inhibit NO and ROS synthesis and PGE2 secretion in lipopolysaccharide (LPS)-activated U937 human monocytic cells (derived from a histiocytoma). In order to define the molecular mechanisms underlying the antiproliferative effects of derivative 2, we found that it determined cell cycle arrest at the G1 phase, modified the expression of cell cycle regulatory proteins, and ultimately triggered apoptotic cell death in both breast cancer cell lines. Taken together, these results highlight the studied RSV derivatives, particularly derivative 2, as promising tools for the development of new and more bioavailable derivatives useful in the treatment of breast cancer

Polymeric materials for biomedical applications: synthesis and characterisation

Dottorato di Ricerca in “Environment, Health and Eco-friendly Processes" XXIII CicloUniversità degli Studi della Calabri

Polysaccharide-Based Hydrogels and Their Application as Drug Delivery Systems in Cancer Treatment: A Review

Hydrogels are three-dimensional crosslinked structures with physicochemical properties similar to the extracellular matrix (ECM). By changing the hydrogel&rsquo;s material type, crosslinking, molecular weight, chemical surface, and functionalization, it is possible to mimic the mechanical properties of native tissues. Hydrogels are currently used in the biomedical and pharmaceutical fields for drug delivery systems, wound dressings, tissue engineering, and contact lenses. Lately, research has been focused on hydrogels from natural sources. Polysaccharides have drawn attention in recent years as a promising material for biological applications, due to their biocompatibility, biodegradability, non-toxicity, and excellent mechanical properties. Polysaccharide-based hydrogels can be used as drug delivery systems for the efficient release of various types of cancer therapeutics, enhancing the therapeutic efficacy and minimizing potential side effects. This review summarizes hydrogels&rsquo; classification, properties, and synthesis methods. Furthermore, it also covers several important natural polysaccharides (chitosan, alginate, hyaluronic acid, cellulose, and carrageenan) widely used as hydrogels for drug delivery and, in particular, their application in cancer treatment

Polysaccharide-Based Hydrogels and Their Application as Drug Delivery Systems in Cancer Treatment: A Review

Hydrogels are three-dimensional crosslinked structures with physicochemical properties similar to the extracellular matrix (ECM). By changing the hydrogel’s material type, crosslinking, molecular weight, chemical surface, and functionalization, it is possible to mimic the mechanical properties of native tissues. Hydrogels are currently used in the biomedical and pharmaceutical fields for drug delivery systems, wound dressings, tissue engineering, and contact lenses. Lately, research has been focused on hydrogels from natural sources. Polysaccharides have drawn attention in recent years as a promising material for biological applications, due to their biocompatibility, biodegradability, non-toxicity, and excellent mechanical properties. Polysaccharide-based hydrogels can be used as drug delivery systems for the efficient release of various types of cancer therapeutics, enhancing the therapeutic efficacy and minimizing potential side effects. This review summarizes hydrogels’ classification, properties, and synthesis methods. Furthermore, it also covers several important natural polysaccharides (chitosan, alginate, hyaluronic acid, cellulose, and carrageenan) widely used as hydrogels for drug delivery and, in particular, their application in cancer treatment