Ana Alcudia

Bio: Ana Alcudia is an academic researcher from University of Seville. The author has contributed to research in topics: Enantioselective synthesis & Osseointegration. The author has an hindex of 16, co-authored 49 publications receiving 628 citations. Previous affiliations of Ana Alcudia include Johnson & Johnson Pharmaceutical Research and Development & Autonomous University of Madrid.

Polymeric Nanoparticles for Drug Delivery: Recent Developments and Future Prospects

Abstract: The complexity of some diseases—as well as the inherent toxicity of certain drugs—has led to an increasing interest in the development and optimization of drug-delivery systems. Polymeric nanoparticles stand out as a key tool to improve drug bioavailability or specific delivery at the site of action. The versatility of polymers makes them potentially ideal for fulfilling the requirements of each particular drug-delivery system. In this review, a summary of the state-of-the-art panorama of polymeric nanoparticles as drug-delivery systems has been conducted, focusing mainly on those applications in which the corresponding disease involves an important morbidity, a considerable reduction in the life quality of patients—or even a high mortality. A revision of the use of polymeric nanoparticles for ocular drug delivery, for cancer diagnosis and treatment, as well as nutraceutical delivery, was carried out, and a short discussion about future prospects of these systems is included.

Environmental Impact of Nanoparticles' Application as an Emerging Technology: A Review.

Abstract: The unique properties that nanoparticles exhibit, due to their small size, are the principal reason for their numerous applications, but at the same time, this might be a massive menace to the environment. The number of studies that assess the possible ecotoxicity of nanomaterials has been increasing over the last decade to determine if, despite the positive aspects, they should be considered a potential health risk. To evaluate their potential toxicity, models are used in all types of organisms, from unicellular bacteria to complex animal species. In order to better understand the environmental consequences of nanotechnology, this literature review aims to describe and classify nanoparticles, evaluating their life cycle, their environmental releasing capacity and the type of impact, particularly on living beings, highlighting the need to develop more severe and detailed legislation. Due to their diversity, nanoparticles will be discussed in generic terms focusing on the impact of a great variety of them, highlighting the most interesting ones for the industry.

Enantiopure Sulforaphane Analogues with Various Substituents at the Sulfinyl Sulfur: Asymmetric Synthesis and Biological Activities

Abstract: A convergent and high-yielding approach for the asymmetric synthesis of sulforaphane 2 and four analogues differently substituted at the sulfinyl sulfur has been developed. The key step of the synthesis is the diastereoselective synthesis of sulfinate ester 23-S(S), using the DAG (diacetone-D-glucofuranose)-methodology. The biological activity of these compounds as inductors of phase II detoxifying enzyme has been studied by determining their ability to activate the cytoprotective transcription factor Nrf2.

Acute oxidant damage promoted on cancer cells by amitriptyline in comparison with some common chemotherapeutic drugs.

Abstract: Oxidative therapy is a relatively new anticancer strategy based on the induction of high levels of oxidative stress, achieved by increasing intracellular reactive oxygen species (ROS) and/or by depleting the protective antioxidant machinery of tumor cells. We focused our investigations on the antitumoral potential of amitriptyline in three human tumor cell lines: H460 (lung cancer), HeLa (cervical cancer), and HepG2 (hepatoma); comparing the cytotoxic effect of amitriptyline with three commonly used chemotherapeutic drugs: camptothecin, doxorubicin, and methotrexate. We evaluated apoptosis, ROS production, mitochondrial mass and activity, and antioxidant defenses of tumor cells. Our results show that amitriptyline produces the highest cellular damage, inducing high levels of ROS followed by irreversible serious mitochondrial damage. Interestingly, an unexpected decrease in antioxidant machinery was observed only for amitriptyline. In conclusion, based on the capacity of generating ROS and inhibiting antioxidants in tumor cells, amitriptyline emerges as a promising new drug to be tested for anticancer therapy.

Additions of Enantiopure α-Sulfinyl Carbanions to (S)-N-Sulfinimines: Asymmetric Synthesis of β-Amino Sulfoxides and β-Αmino Alcohols

Abstract: The addition of the lithium anions derived from (R)- and (S)-methyl and -ethyl p-tolyl sulfoxides to (S)-N-benzylidene-p-toluenesulfinamide provides an easy access route to enantiomerically pure β-(N-sulfinyl)amino sulfoxides. Stereoselectivity can be achieved when the configurations at the sulfur atoms of the two reagents are opposite (matched pair), thus resulting in only one diastereoisomer, even for the case in which two new chiral centers are created. The N-sulfinyl group primarily controls the configuration of the carbon bonded to the nitrogen, whereas the configuration of the α-sulfinyl carbanion seems to be responsible for the level of asymmetric induction, as well as for the configuration of the new stereogenic C−SO carbon in the reactions with ethyl p-tolyl sulfoxides. An efficient method for transforming the obtained β-(N-sulfinyl)amino sulfoxides into optically pure β-amino alcohols, based on the stereoselective non-oxidative Pummerer reaction, is also reported.

Calcimimetics with potent and selective activity on the parathyroid calcium receptor (cytoplasmic Ca21yhyperparathyroidismyparathyroid cellsyNPS R-568yNPS R-467)

Abstract: Parathyroid hormone (PTH) secretion is reg-ulated by a cell surface Ca 2 1 receptor that detects small changesin the level of plasma Ca 2 1 . Because this G protein-coupledreceptor conceivably provides a distinct molecular target fordrugs useful in treating bone and mineral-related disorders, wesought to design small organic molecules that act on the Ca 2 1 receptor. We discovered that certain phenylalkylamine com-pounds, typified by NPS R-568 and its deschloro derivative NPSR-467, increased the concentration of cytoplasmic Ca 2 1 ([Ca 2 1 ] i ) in bovine parathyroid cells and inhibited PTH secre-tion at nanomolar concentrations. These effects were stereose-lective and the R enantiomers were 10- to 100-fold more potentthan the S enantiomers. NPS R-568 potentiated the effects ofextracellular Ca 2 1 on [Ca 2 1 ] i and PTH secretion but waswithout effect in the absence of extracellular Ca 2 1 . Both com-pounds shifted the concentration–response curves for extracel-lular Ca 2 1 to the left. Presumably, these compounds act aspositive allosteric modulators to increase the sensitivity of theCa