University of Medicine and Pharmacy, Cluj-Napoca
Emil Racovita, Romania
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Leucuta S.E.,University of Medicine and Pharmacy, Cluj-Napoca
Journal of Drug Targeting | Year: 2014

Effective treatment of diseases at the molecular level is possible by directing the drug substance (micromolecular, protein or peptide drugs, DNA, oligonucleotides, siRNA) with the aid of a specialized nanoparticulate carrier, for safe and effective transport to the specific site of action in the cytosol and its organelles including nuclear targeting. To achieve efficient cytosolic delivery of therapeutics or nuclear targeting, different drug delivery systems (DDS) have been developed (macromolecular drug conjugates, chemically or genetically modified proteins, and particulate drug carriers) capable of subcellular internalization overcoming the biological barriers, by passive targeting and especially by active targeting (receptor-targeted delivery). The success depends on the physicochemical nature of DDS, intracellular barriers that these systems need to overcome, the bioavailability of the bioactive drug, biodistribution, the intracellular pharmacokinetics and its influence on the pharmacodynamic effect. Models necessary for this purpose exist but they need to be more developed especially with quantitative treatments, after the development of the means of highlighting the evolution of the drug substance in biophase or at the level of the target cellular organelle by quantitative assays. It is expected that intracellularly targeted drug delivery approaches will be clinically useful using specialized DDSs belonging to the pharmaceutical nanotechnologies. © 2014 Informa UK Ltd.

Leucuta S.E.,University of Medicine and Pharmacy, Cluj-Napoca
Current Drug Delivery | Year: 2013

The development of the vectorized delivery systems combining advantages of the colloidal carriers, with active targeting to the receptors sites suggests that nanoparticles have a considerable potential for treatment after biophase internalization and pharmacokinetics, as for example gene therapy. Two major mechanisms can be distinguished for addressing the desired sites for drug release: (i) passive and (ii) active targeting. Examples of passive targeting were presented: organ targeting by the Enhanced Permeability and Retention (EPR) effect; targeting the mononuclear phagocitic system; organ targeting by chemoembolization or local (organ) administration;sterical stabilization of nanoparticles (PEGylation). A strategy that could allow active targeting involves the surface functionalization of drug carriers with ligands that are selectively recognized by receptors on the surface of the cells of interest. The source for biophase bioavailability can be the systemic bioavailability following common routes of adminstration (generally for systemic delivery of medicines), or directly the site specific biophase bioavailability for the formulations capable of cellular or nuclear drug internalization where the drug release only will take place (for nanoparticulate drug delivery systems, DDS). Once the pharmaceutical nanosystem was internalized, begins the release of the active moiety by different mechanisms, as for example the escape from endosome, or biodegradation of the polymer carrier or liberation of the active peptide or gene from a biological construct in the nucleus, etc. The presentation will discusses the pharmacokinetics of drugs after systemic administration but especially the biophase bioavailability and pharmacokinetics after the administration of biotechnology origin of therapeutic proteins like monoclonal antibodies, gene transfer products, plasmid DNAs, nucleotides, antisense oligonucleotides (AODNs) or small interfering RNAs (siRNA). © 2013 Bentham Science Publishers.

Albu S.,University of Medicine and Pharmacy, Cluj-Napoca
Drug Design, Development and Therapy | Year: 2012

Chronic rhinosinusitis, one of the most common chronic medical complaints in the United States, seems to be increasing in incidence and prevalence, and has a significant impact on quality of life. Topical forms of medical therapy represent an attractive alternative for drug delivery to the nasal cavity and paranasal sinuses. Topical drug delivery has the advantage of directly acting on the site of inflammation, producing a higher concentration at the target site while avoiding systemic side effects. Although considerable research has been undertaken into improving nasal formulations in order to enhance absorption, little attention has so far been directed to upgrading the delivery devices. The aim of this review is to present current knowledge on the novel drug-delivery devices in use in the management of chronic rhinosinusitis patients, and to present the current available knowledge on topical drug penetration into the sinuses using various delivery devices. Additionally, methods used to enhance fluid sinus deposition are presented and the published clinical studies on the results of nebulized antibiotics in the treatment of chronic rhinosinusitis patients are discussed. © 2012 Albu, publisher and licensee Dove Medical Press Ltd.

Berindan-Neagoe I.,University of Medicine and Pharmacy, Cluj-Napoca | Monroig P.D.C.,University of Houston | Monroig P.D.C.,University of Puerto Rico at San Juan | Pasculli B.,University of Puerto Rico at San Juan | And 2 more authors.
CA Cancer Journal for Clinicians | Year: 2014

The interplay between abnormalities in genes coding for proteins and noncoding microRNAs (miRNAs) has been among the most exciting yet unexpected discoveries in oncology over the last decade. The complexity of this network has redefined cancer research as miRNAs, produced from what was once considered "genomic trash," have shown to be crucial for cancer initiation, progression, and dissemination. Naturally occurring miRNAs are very short transcripts that never produce a protein or amino acid chain, but act by regulating protein expression during cellular processes such as growth, development, and differentiation at the transcriptional, posttranscriptional, and/or translational level. In this review article, miRNAs are presented as ubiquitous players involved in all cancer hallmarks. The authors also describe the most used methods to detect their expression, which have revealed the identity of hundreds of miRNAs dysregulated in cancer cells or tumor microenvironment cells. Furthermore, the role of miRNAs as hormones and as reliable cancer biomarkers and predictors of treatment response is discussed. Along with this, the authors explore current strategies in designing miRNA-targeting therapeutics, as well as the associated challenges that research envisions to overcome. Finally, a new wave in molecular oncology translational research is introduced: the study of long noncoding RNAs. © 2014 American Cancer Society.

Mocan L.,University of Medicine and Pharmacy, Cluj-Napoca
International journal of nanomedicine | Year: 2011

The process of laser-mediated ablation of cancer cells marked with biofunctionalized carbon nanotubes is frequently called "nanophotothermolysis". We herein present a method of selective nanophotothermolisys of pancreatic cancer (PC) using multiwalled carbon nanotubes (MWCNTs) functionalized with human serum albumin (HSA). With the purpose of testing the therapeutic value of these nanobioconjugates, we have developed an ex-vivo experimental platform. Surgically resected specimens from patients with PC were preserved in a cold medium and kept alive via intra-arterial perfusion. Additionally, the HSA-MWCNTs have been intra-arterially administered in the greater pancreatic artery under ultrasound guidance. Confocal and transmission electron microscopy combined with immunohistochemical staining have confirmed the selective accumulation of HSA-MWCNTs inside the human PC tissue. The external laser irradiation of the specimen has significantly produced extensive necrosis of the malign tissue after the intra-arterial administration of HSA-MWCNTs, without any harmful effects on the surrounding healthy parenchyma. We have obtained a selective photothermal ablation of the malign tissue based on the selective internalization of MWCNTs with HSA cargo inside the pancreatic adenocarcinoma after the ex-vivo intra-arterial perfusion.

Iancu C.,University of Medicine and Pharmacy, Cluj-Napoca
International journal of nanomedicine | Year: 2011

Carbon nanotubes (CNTs) are emerging versatile tools in nanomedicine applications, particularly in the field of cancer targeting. Due to diverse surface chemistry and unique thermal properties, CNTs can act as strong optical absorbers in near infrared light where biological systems prove to be highly transparent. The process of laser-mediated ablation of cancer cells marked with biofunctionalized CNTs is frequently termed "nanophotothermolysis." This paper illustrates the potential of engineered CNTs as laser-activated photothermal agents for the selective nanophotothermolysis of cancer cells.

Mocan T.,University of Medicine and Pharmacy, Cluj-Napoca
International journal of nanomedicine | Year: 2011

In recent years, a new concept of an anticancer vaccine has been proposed to prevent and control the proliferation and expansion of cancer cells by eliciting an immune boost in biological systems. The recent literature supports the role of embryonic stem cells (ESC) as cellular agents that stimulate the biological systems to destroy cancer cells. However, at present, a true anticancer vaccine remains elusive. There are several lines of evidence showing that carbon nanotubes may be used to initiate and maintain immune responses. The authors proposed to test the therapeutic potential of multiwalled carbon nanotubes (MWCNTs) combined with ESC as agents to induce an immune boost and provide subsequent anticancer protection in mice. C57 BL/6 mice were immunized with ESC and MWCNTs. The proposed vaccine led to significant antitumor responses and enhanced tumor rejection in mice with subcutaneous inoculation of MC38 colon malign cells compared with groups only administered ESC, only MWCNTs, and controls. The application and potential of ESC combined with MWCNTs as anticancer immunization agents may represent the beginning of a new chapter in the treatment of colon cancer.

Seicean A.,University of Medicine and Pharmacy, Cluj-Napoca
World Journal of Gastroenterology | Year: 2014

Pain in pancreatic cancer is often a major problem of treatment. Administration of opioids is frequently limited by side effects or insufficient analgesia. Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) represents an alternative for the palliative treatment of visceral pain in patients with pancreatic cancer. This review focuses on the indications, technique, outcomes of EUS-CPN and predictors of pain relief. EUS-CPN should be considered as the adjunct method to standard pain management. It moderately reduces pain in pancreatic cancer, without eliminating it. Nearly all patients need to continue opioid use, often at a constant dose. The effect on quality of life is controversial and survival is not influenced. The approach could be done in the central position of the celiac axis, which is easy to perform, or in the bilateral position of the celiac axis, with similar results in terms of pain alleviation. The EUS-CPN with multiple intraganglia injection approach seems to have better results, although extended studies are still needed. Further trials are required to enable more confident conclusions regarding timing, quantity of alcohol injected and the method of choice. Severe complications have rarely been reported, and great care should be taken in choosing the site of alcohol injection. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

Leucuta S.E.,University of Medicine and Pharmacy, Cluj-Napoca
Expert Opinion on Drug Discovery | Year: 2014

Introduction: The role of chemical structure, lipophilicity, physico-chemical, absorption, distribution, metabolism, excretion, toxicity (ADMET) and biopharmaceutical properties of compounds including bioavailability are critical in drug discovery and drug dosage forms design. Areas covered: The authors discuss a number of parameters including computational approaches used for selected chemical structures with biological activity for lead optimization and chemogenomics and preclinical studies for ADMET process development of ligand properties. The authors also look at a number of other parameters including: early drug product formulations with method selection based on the biopharmaceutical classification system (BCS); in vitro-in vivo correlation (IVIVC) and different formulation strategies to enhance solubility; dissolution rate and permeability; bioavailability evaluation and quality by design as an opportunity to develop 'safe space' regions, where bioavailability is unaffected by pharmaceutical variations. Expert opinion: The biopharmaceutical requirements for absorption are solubility and permeability. Both are influenced by lipophilicity, but in the opposite way. The genomic methodology, coupled with combinatorial chemistry, high-throughput screening, structure-based design and in silico ADMET would yield parameters as a starting point for the biopharmaceutical properties determination in further preclinical and clinical studies. Consecutive stages in drug discovery and development are irreplaceable, but pharmacokinetics is the critical step. Selection of drug formulations based on the BCS, IVIVC are the principal aspects to enhance the solubility and dissolution rate, while a rationale management of pharmaceutical and technological factors will enhance the bioavailability. © 2014 Informa UK, Ltd.

Acalovschi M.,University of Medicine and Pharmacy, Cluj-Napoca
World Journal of Gastroenterology | Year: 2014

Gallstones occur in about one third of the patients having liver cirrhosis. Pigment gallstones are the most frequent type, while cholesterol stones represent about 15% of all stones in cirrhotics. Increased secretion of unconjugated bilirubin, increased hydrolysis of conjugated bilirubin in the bile, reduced secretion of bile acids and phospholipds in bile favor pigment lithogenesis in cirrhotics. Gallbladder hypomotility also contributes to lithogenesis. The most recent data regarding risk factors for gallstones are presented. Gallstone prevalence increases with age, with a ratio male/female higher than in the general population. Chronic alcoholism, viral C cirrhosis, and non-alcoholic fatty liver disease are the underlying liver diseases most often associated with gallstones. Gallstones are often asymptomatic, and discovered incidentally. If asymptomatic, expectant management is recommended, as for asymptomatic gallstones in the general population. However, a closer follow-up of these patients is necessary in order to earlier treat symptoms or complications. For symptomatic stones, laparoscopic cholecystectomy has become the therapy of choice. Child-Pugh class and MELD score are the best predictors of outcome after cholecystectomy. Patients with severe liver disease are at highest surgical risk, therefore gallstone complications should be treated using noninvasive or minimally invasive procedures, until stabilization of the patient condition. © 2014 Baishideng Publishing Group Inc. All rights reserved.

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