BIOCOMPATIBLE TARGETING HYDROGELS FOR BREAST CANCER TREATMENT.

Hydrogels have received growing attention as materials for drug delivery systems (DDS) because of their biodegradable and biocompatible properties. DDS were developed to optimize the therapeutic properties of drug products and to render them more safe, effective, and reliable. In the past, drugs were frequently administered orally, as liquids or in powder forms. To avoid problems incurred through the utilization of the oral route of administration, new dosage forms, DDS, containing the drugs were introduced. They can deliver drugs directly to the intended site of action and can also improve treatment efficacy, while minimizing unwanted side effects elsewhere in the body, which often limit the long-term use of many drugs, and provide better efficacy of treatment. Biocompatible hydrogels are an example of such systems available for therapeutic use. In this review, results from recent publications concerning these systems are discussed. Hydrogels show superior effectiveness over conventional methods of treatment providing controlled release of active substances. They are of interest in medical applications such as breast cancer treatment.

Novel PEG-coated niosomes based on bola-surfactant as drug carriers for 5-fluorouracil.

Innovative niosomes made up of α,ω-hexadecyl-bis-(1-aza-18-crown-6) (bola), Span 80® and cholesterol (2:5:2 molar ratio) are proposed as suitable delivery systems for the administration of 5-fluorouracil (5-FU), an antitumoral compound largely used in the treatment of breast cancer. The bola-niosomes, after sonication procedure, showed mean sizes of ~200 nm and a loading capacity of ~40% with respect to the amount of 5-FU added during the preparation. Similar findings were achieved with PEG-coated bola-niosomes (bola, Span 80(R), cholesterol, DSPE-mPEG2000, 2:5:2:0.1 molar ratio respectively). 5-FU-loaded PEG-coated and uncoated bola-niosomes were tested on MCF-7 and T47D cells. Both bola-niosome formulations provided an increase in the cytotoxic effect with respect to the free drug. Confocal laser scanning microscopy studies were carried out to evaluate both the extent and the time-dependent bola-niosome-cell interaction. In vivo experiments on MCF-7 xenograft tumor SCID mice models showed a more effective antitumoral activity of the PEGylated niosomal 5-FU at a concentration ten times lower (8 mg/kg) than that of the free solution of the drug (80 mg/kg) after a treatment of 30 days.

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.

Synthesized esters of ferulic acid induce release of cytochrome c from rat testes mitochondria.

Ferulic acid plays a chemopreventive role in cancer by inducing tumor cells apoptosis. As mitochondria play a key role in the induction of apoptosis in many cells types, here we investigate the mitochondrial permeability transition (MPT) and the release of cytochrome c induced by ferulic acid and its esters in rat testes mitochondria, in TM-3 and MLTC-1 cells. While ferulic acid, but not its esters, induced MPT and cytochrome c release in rat testes isolated mitochondria, in TM-3 cells we found that both ferulic acid and its esters induced cytochrome c release from mitochondria in a dose-dependent manner, suggesting a potential target of these compounds in the induction of cell apoptosis. The apoptosis induced by ferulic acid is therefore associated with the mitochondrial pathway involving cytochrome c release and caspase-3 activation.

Molecularly imprinted solid phase extraction for the selective HPLC determination of alpha-tocopherol in bay leaves.

A new sorbent for molecularly imprinted solid phase extraction (MISPE) was synthesized to extract and purify alpha-tocopherol (alpha-TP) from vegetable sources. Molecularly imprinted polymers (MIP) were synthesized using methacrylic acid (MAA) as functional monomer and ethylene glycol dimethacrylate (EGDMA) as crosslinking agent using a photo-polymerization procedure. A thermo-polymerization was also performed but no imprinting effect in the resulting materials was raised. The proposed MISPE protocol could overcome the drawback of traditional detection methods, which require pre-treatments of the samples. The possibility to obtain the selective recognition of alpha-TP from natural samples in aqueous mixtures represents one of the main advantages of our materials. Our procedure involves the direct HPLC injection of eluate without any treatment and above all the use of no toxic and biocompatible organic solvents. After the evaluation of the selectivity of the alpha-TP imprinted polymers, the performance of these materials as solid phase extraction (SPE) sorbents was investigated. Our MISPE-HPLC procedure has a high sensitivity, LOD and LOQ were 3.49x10(-7) and 1.16x10(-6) mol L(-1), respectively, as well as good precision (intraday precision below 3.3% and interday precisions below 6.5%) and recovery (60%). Thus, it can be successfully used for the purification of alpha-TP from bay leaves.

Radical cross-linked albumin microspheres as potential drug delivery systems: preparation and in vitro studies.

The aim of this research is the preparation of acryloylated bovine serum albumin microspheres and the evaluation of their employment in drug delivery. The influence of preparation parameters on albumin microspheres and the chemicophysical properties of loaded drugs were investigated. In particular, we focused our attention on acylation albumin degree, amount of acryloylated albumin against comonomer in the polymerization step, and finally the release profile. We considered on the interaction drug-matrix, the fuctionalization degree of albumin, and the water affinity of matrix.

Radical crosslinked albumin microspheres as potential drug delivery systems: preparation and in vitro studies.

This article reports on the preparation of acryloylated bovine serum albumin microspheres and the evaluation of their employment in drug delivery areas. The influence of preparation parameters on albumin microspheres and the chemicophysical properties of loaded drugs were investigated. In particular, we focussed on acylation albumin degree and the amount of acryloylated albumin against comonomer in the polymerization step. Finally the release profile took into consideration the interaction drug-matrix, the fuctionalization degree of albumin, and the water affinity of matrix.

Spherical molecularly imprinted polymers (SMIPs) via a novel precipitation polymerization in the controlled delivery of sulfasalazine.

Spherical molecularly imprinted polymers (SMIPs) have been prepared via a novel precipitation polymerization using sulfasalazine (prodrug used in the diseases of the colon) as template. The sulfasalazine was incorporated into SMIPs and into a spherical non-imprinted polymer (control), and then the release rate of the bioactive agent at different pH values was evaluated. Considerable differences in the release characteristics between imprinted and non-imprinted polymers have been observed. This opens the possibility of the development of drug release systems capable of modulating the release of a specific molecule. Photomicrography of spherical molecularly imprinted polymers (SMIPs).

Drug release from alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide-based microparticles.

Spherical pH-sensitive microparticles have been prepared by reverse phase suspension polymerization technique. Starting polymer has been alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) partially derivatized with glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) has been crosslinked in the presence of acrylic acid (AA) or methacrylic acid (MA) at various concentration. The obtained microparticles have been characterized by FT-IR spectrophotometry, particle size distribution analysis and scanning electron microscopy. In order to have information about water affinity of the prepared samples, swelling measurements have been carried out in aqueous media which simulate some biological fluids. The possibility to employ the prepared samples as pH-sensitive microparticles has been investigated by performing in vitro release studies. Experimental data have showed that the release rate from these microparticles depends on the environmental pH and the chemical structure of the drug.

Beads of acryloylated polyaminoacidic matrices containing 5-Fluorouracil for drug delivery.

Spherical polymeric microparticles have been prepared by a reverse phase suspension polymerization technique. The starting polymer was alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA), partially derivatized with glycidylmethacrylate (GMA). PHEA-GMA copolymer (PHG) was crosslinked in the presence of N,N'-dimethylacrylamide (DMAA) or N,N'-ethylenebisacrylamide (EBA). 5-fluorouracil was incorporated into PHG-DMAA or PHG-EBA beads both during and after the crosslinking process. Swelling studies revealed a high affinity toward aqueous medium, influenced by the presence of 5-fluorouracil. The in vitro release study showed that the release rate depends on the chemical structure of the beads and the procedure adopted to incorporate 5-fluorouracil into the microparticles.