M. Adolfina Ruiz

5-Fluorouracil-loaded poly(ε-caprolactone) nanoparticles combined with phage E gene therapy as a new strategy against colon cancer.

This work aimed to develop a new therapeutic approach to increase the efficacy of 5-fluorouracil (5-FU) in the treatment of advanced or recurrent colon cancer. 5-FU-loaded biodegradable poly(ε-caprolactone) nanoparticles (PCL NPs) were combined with the cytotoxic suicide gene E (combined therapy). The SW480 human cancer cell line was used to assay the combined therapeutic strategy. This cell line was established from a primary adenocarcinoma of the colon and is characterized by an intrinsically high resistance to apoptosis that correlates with its resistance to 5-FU. 5-FU was absorbed into the matrix of the PCL NPs during synthesis using the interfacial polymer disposition method. The antitumor activity of gene E from the phage ϕX174 was tested by generating a stable clone (SW480/12/E). In addition, the localization of E protein and its activity in mitochondria were analyzed. We found that the incorporation of 5-FU into PCL NPs (which show no cytotoxicity alone), significantly improved the drug’s anticancer activity, reducing the proliferation rate of colon cancer cells by up to 40-fold when compared with the nonincorporated drug alone. Furthermore, E gene expression sensitized colon cancer cells to the cytotoxic action of the 5-FU-based nanomedicine. Our findings demonstrate that despite the inherent resistance of SW480 to apoptosis, E gene activity is mediated by an apoptotic phenomenon that includes modulation of caspase-9 and caspase-3 expression and intense mitochondrial damage. Finally, a strongly synergistic antiproliferative effect was observed in colon cancer cells when E gene expression was combined with the activity of the 5-FU-loaded PCL NPs, thereby indicating the potential therapeutic value of the combined therapy.

Formulation and physicochemical characterization of poly(ɛ-caprolactone) nanoparticles loaded with ftorafur and diclofenac sodium

Even though conventional pharmacotherapy has been demonstrated to display very efficient activity against a wide variety of diseases, several active agents (e.g., anti-tumor drugs and non-steroidal anti-inflammatory drugs) are generally needed to be administered at high doses to elicit the required therapeutic action, simultaneously leading to severe side effects. This fact is usually due to unfavourable pharmacokinetic profiles (poor biological half-life) and to the possibility of induction of resistance. In order to increase the therapeutic activity of ftorafur and diclofenac sodium along with an overcome of their important drawbacks, we investigated their formulation into a colloidal carrier based on the biodegradable polymer poly(epsilon-caprolactone). Two drug loading methods were studied: (i) surface adsorption in already formed nanoparticles after incubation in a drug solution; (ii) drug addition before interfacial polymer disposition leading to drug entrapment into the polymeric network. We hypothesized that such nanocarrier possessed very significant characteristics (e.g., unusually high drug loading and low burst release), suggesting their potential application for efficient drug delivery to targeted sites.

Vesicular Lipidic Systems, Liposomes, PLO, and Liposomes–PLO: Characterization by Electronic Transmission Microscopy

Situations exist in which rapid administration of treatment, as well as maintenance of efficient concentrations for the longest possible time, turns out to be essential. In view of the previous treatment, the elaboration of liposomes, PLO (pluronic lecithin organogel), and the mixture of both is described, as well as their characterizations by electronic transmission microscopy, with the aim of finding out precisely the type of structure for both controlled release systems, its composition, size, homogeneity, and integrity. The period of study has been 90 days. Multilaminar and unilaminar vesicles smaller than 1 μm in diameter were seen in the liposomes, PLO, and liposomes–PLO formulations on transmission electron microscopic (TEM) observation. The technique of characterization reveals the progressive aggregation of the liposomas along the period of study. However, all the vesicles of PLO maintain a defined structure and only a light aggregation 60 days after the elaboration. Changes of morphology and aggregation of liposomas decreased after the incorporation of cholesterol (CH) to the liposomal matrix. The best results were obtained with the formulas liposomes–PLO, which maintain their individuality and integrity during the whole period of study. The combined formulation of liposomas and PLO showed an increase of stability of both lipid systems.

Skin Creams Made with Olive Oil

Publisher Summary Olive oil and its derivatives are extensively used in the preparation of many pharmaceutical formulations for therapeutic or cosmetic applications. When a drug is included in these preparations, a local or systemic effect is achieved. Because of its properties, olive oil can act as an active agent by itself or as an excipient of several formulations. Oleic acid and the unsaponifiable fraction are two components of olive oil very important in health care. The unsaponifiable fraction of olive oil can be considered as an active agent by itself, and oleic acid is used in the elaboration of topic formulations as excipient but can also act as a percutaneous absorption enhancer of several drugs. Olive oil also contains oleocantal, a cyclooxygenase inhibitor with anti-inflammatory and analgesic properties similar to the non-steroidal anti-inflammatory drug ibuprofen. Furthermore, olive oil and oleic acid have been tested in the preparation of drug delivery systems with very promising results.

WITHDRAWN: 5-Fluorouracil-loaded iron/ethylcellulose (core/shell) nanoparticles for active targeting of cancer

Even though 5-fluorouracil has been demonstrated to display antitumor activity against a wide variety of cancers, it is needed to be administered at high doses to elicit the required therapeutic activity, simultaneously leading to severe side effects. We hypothesized that the efficient delivery of 5-fluorouracil to tumors using a magnetic colloid could reduce the dose required to bring out sufficient therapeutic response. Thus, we have formulated a 5-fluorouracil-loaded magnetic nanomedicine consisting of a magnetic core (iron) and a biocompatible polymeric shell (ethylcellulose), suitable for parenteral administration. These core/shell nanoparticles were synthesized by an emulsion solvent evaporation process. Two drug loading methods were analyzed: the first one based on 5-fluorouracil surface adsorption onto the preformed nanoparticles, and the second method being drug addition prior to the emulsion solvent evaporation process leading to drug entrapment into the polymeric network. 5-Fluorouracil entrapment into the polymeric matrix yielded a higher drug loading and a slower drug release profile as compared with drug adsorption. Finally, as a proof of concept, Prussian blue staining has demonstrated the considerable accumulation of these magnetically guided composite nanoparticles in the tumors, suggesting the potential of this stimuli-sensitive drug carrier for the efficient treatment of cancer by active targeting.

Multifunctional anticancer nanomedicine based on a magnetically responsive cyanoacrylate polymer.

The therapeutic effect of antitumor molecules (efficacy and safety) is severely limited by their poor pharmacokinetic characteristics. Recently, the use of colloids has been proposed for the delivery of anticancer drugs to tumor cells, thereby providing a significant advance toward new treatments with improved specificity. In this respect, magnetically responsive nanopolymers are probably one of the most promising materials. In this contribution, we describe the basic steps to be followed in the development of such composite nanoplatforms. Starting from the formulation procedure, we detail the physicochemical engineering of these nanomedicines for combined antitumor activities (anticancer drug delivery plus hyperthermia effect). The key features determining drug incorporation to the nanomaterial are analyzed. Such stimuli-sensitive nanoparticles have promising properties (e.g., blood compatibility, hyperthermia, magnetic targeting capabilities, high drug loading, and little burst drug release), which could be used for efficient multifunctional anticancer therapy.