Giuseppe Cirillo

Covalent Insertion of Antioxidant Molecules on Chitosan by a Free Radical Grafting Procedure

In this work, the synthesis of gallic acid-chitosan and catechin-chitosan conjugates was carried out by adopting a free radical-induced grafting procedure. For this purpose, an ascorbic acid/hydrogen peroxide redox pair was employed as radical initiator. The formation of covalent bonds between antioxidant and biopolymer was verified by performing UV, FT-IR, and DSC analyses, whereas the antioxidant properties of chitosan conjugates were compared with that of a blank chitosan, treated in the same conditions but in the absence of antioxidant molecules. The good antioxidant activity shown by functionalized materials proved the efficiency of the reaction method.

Molecularly imprinted polymers in drug delivery: state of art and future perspectives

Introduction: Molecularly imprinted polymers (MIPs) are synthetic receptors, characterized by a high selectivity for the selected template. Among the different applications of MIPs, their use as controlled/sustained drug delivery devices has been extensively explored, even though the optimization of such devices needs to be performed before they are applied in clinical practice. Areas covered: Within drug delivery, one of the most promising fields is the possibility to modulate the drug release profile in response to a specific external stimulus; MIPs represent potentially suitable vehicles, because of the possibility to insert a stimuli-responsive co-monomer in their structure. This review discusses recent advances in the use of external stimuli to modulate drug release, as well as the synthetic strategies devoted to increase the water compatibility of these systems, which is a base requirement for their application in biomedicine. Expert opinion: Although it is easy to imagine imprinted polymers for biomedical applications, several aspects have to be further investigated, such as the in vivo studies, efficiency and biocompatibility. However, we think that in the next few years it will possible to see unprecedented progress in the preparation of such systems and the translational application of these intelligent structures in medicine.

Molecularly imprinted polymers for the selective extraction of glycyrrhizic acid from liquorice roots

Abstract A new Molecularly Imprinted Solid Phase Extraction (MISPE) protocol was developed for the selective extraction and purification of glycyrrhizic acid (GL) from liquorice roots. Non-covalent MIP were synthesized using methacrylic acid (MAA), 2-(dimethylamino)ethyl methacrilate (DMAEM) or 2-hydroxyethylmetacrylate (HEMA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. After the evaluation of the selectivity of the GL imprinted polymers, the performance of these materials as Solid Phase Extraction (SPE) sorbents was investigated. MIP having HEMA as functional monomer were found to be able to selectively extract almost 80% of GL content in liquorice roots. The proposed MISPE-HPLC procedure has good precision, thus it can be successfully used for the purification of GL from natural sources.

Imprinted hydrophilic nanospheres as drug delivery systems for 5-fluorouracil sustained release

Molecularly imprinted hydrogel nanospheres as devices for the controlled/sustained release of 5-fluororacil in biological fluids were synthesized employing one-pot precipitation technique as the polymerization method. Methacrylic acid as a functional monomer and ethylene glycole dimethacrylate as a cross-linker were used in polymeric feed. Morphological and hydrophilic properties were determined by scanning electron microscopy and water content measurement, and recognition and selectivity properties of spherical molecularly imprinted polymers were compared with the spherical non-imprinted polymers, both in organic (acetonitrile) and water media. Finally, in vitro release studies were performed in plasma simulating fluids.

Molecularly Imprinted Polymers for 5-Fluorouracil Release in Biological Fluids

The aim of this work was to investigate the possibility of employing Molecularly Imprinted Polymers (MIPs) as a controlled release device for 5-fluorouracil (5-FU) in biological fluids, especially gastrointestinal ones, compared to Non Imprinted Polymers (NIPs). MIPs were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent. The capacity of the polymer to recognize and to bind the template selectively in both organic and aqueous media was evaluated. An in vitro release study was performed both in gastrointestinal and in plasma simulating fluids. The imprinted polymers bound much more 5-Fu than the corresponding non-imprinted ones and showed a controlled/sustained drug release, with MIPs release rate being indeed much more sustained than that obtained from NIPs. These polymers represent a potential valid system for drug delivery and this study indicates that the selective binding characteristic of molecularly imprinted polymers is promising for the preparation of novel controlled release drug dosage form.

Grafted thermo-responsive gelatin microspheres as delivery systems in triggered drug release

In this paper, a novel class of microspheric hydrogels was synthesized by grafting of N-isopropyacrylamide (NIPAAm) with gelatin. The possibility of inserting commercial gelatin in a crosslinked structure bearing thermo-sensitive moieties, by radical process, represents an interesting innovation that significantly improves the device performance, opening new applications in biomedical and pharmaceutical fields. This synthetic approach allows a modification of the polymeric network composition, producing hydrogels with suitable physico-chemical properties and a transition temperature higher than NIPAAm homopolymers. The incorporation of monomers into the network was confirmed by infrared spectroscopy, and the composition of the polymerization feed was found to strictly influence the network density and the shape of hydrogels. Thermal analyses showed negative thermo-responsive behaviour with shrinking/swelling transition values in the temperature range 34.6-34.8 degrees C, according to the amount of the hydrophilic portions in the network. In order to test the preformed materials as drug carriers, diclofenac sodium salt was loaded into the spherical microparticles. After the determination of the drug entrapment percent, drug release profiles in media at different temperature were analysed. By using semi-empirical equations, the release mechanism was extensively studied and the diffusional contribution was evaluated.

Biological Activity of a Gallic Acid−Gelatin Conjugate

Goal of the present study was the characterization of the biological properties of a gelatin-gallic acid conjugate (Gel-GA) to evaluate its applicability in biomedicine and pharmacy. The macromolecular conjugate was synthesized by free radical grafting reaction between gelatin and gallic acid (GA) to form a covalent conjugate that was found to retain the antioxidant and enzymatic activities of free GA. In particular, the peroxynitrite scavenging power was found to be consistent with a IC(50) value of 2.17 ± 0.4 mg mL(-1). The enzymatic capacities of GA, which are regarded beneficial for cell functions, are partly retained in the Gel-GA conjugate. In particular, acetylcholinesterase inhibition (IC(50) of 7.1 ± 1.3 mg mL(-1)) implies the conjugates usefulness in the chemoprevention of Alzheimers disease, while the inhibition of α-amylase (IC(50) of 9.8 ± 1.1 mg mL(-1)) suggests that the conjugate can be a preferred alternative for inhibition of carbohydrate breakdown and control of glycemic index of food products. Finally, the anticancer activity of Gel-GA was proven in prostate carcinoma and renal cell carcinoma cell lines, confirming the potential of the proposed protein-polyphenol conjugate in medicine.

Dextran-Catechin Conjugate: A Potential Treatment Against the Pancreatic Ductal Adenocarcinoma

ABSTRACTPurposeA polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC).MethodsThe conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated.ResultsBoth the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells.ConclusionThe suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy.

Graphene oxide-based drug delivery vehicles: functionalization, characterization, and cytotoxicity evaluation

Abstract As a consequence of graphene oxides (GOs) high chemical versatility, there is great interest in functionalized as a nanocarrier for in vitro and in vivo drug delivery. Within this review, the structure and properties of GO that allow covalent and non-covalent functionalization are discussed. In short, toxicity investigations show functionalized GO is biocompatible. Various works demonstrate the potential of GO derivatives as exciting nanocarriers for the loading and delivery of therapeutic drugs.

Enhancing the therapeutic effects of polyphenols with macromolecules

Well-known for their antioxidant properties, polyphenols are naturally occurring compounds containing one or more phenol groups. A high dietary intake of polyphenols has been linked to a reduced incidence of a number of diseases, including cancer, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases. Furthermore, in vitro and in vivo studies show the potential for polyphenols as therapeutic agents with cardioprotective, antimicrobial, anticancer, neuroprotective, and antidiabetic effects demonstrated. Despite their impressive therapeutic effects, polyphenols suffer from a number of drawbacks, including instability when exposed to light, heat and basic conditions; poor bioavailability; rapid metabolism; and poor membrane permeability. These drawbacks limit the clinical applications of polyphenols. Polymers and other macromolecules are well-known for their ability to stabilise and improve the bioavailability of therapeutic agents. A number of macromolecular systems have been developed that stabilise polyphenols whilst enhancing their therapeutic effects, including direct polymerisation of polyphenol monomers via step-growth, free radical and enzyme catalysed reactions; and conjugation with macromolecules via enzyme grafting, free-radical grafting, esterification and amidation. In this review, we will detail the key techniques employed to stabilise polyphenols with macromolecules and provide examples of each technique.