Current Drug Therapy - Volume 7, Issue 4, 2012

This review focuses on the recent developments and future trends dealing with its modifications, encompassing the different grades of polymethacrylates polymers based formulations. The last three decades of pioneering works explain it as a new functional material of high potential value in novel drug delivery. Polymethacrylates are synthetic cationic and anionic copolymers of dimethylaminoethyl methacrylates, methacrylic acid, and methacrylic acid esters in varying ratios, generating a new and modified patterned polymer due to their electrical characters and pH- dependent solubility. Based on current research and existing products, some new and futuristic approaches in this fascinating area have been thoroughly explored and discussed. These polymers are used as release retardant in different formulations like oral capsules and tablets, film-coating agents for protective purposes and provide sustained release formulations. This review also screens the current applications of these polymers in the development of microparticles, patches, nanoparticles, colon targeted formulations, ophthalmic, vaccine delivery, taste masking agent and its pivotal application in gene delivery systems. This work summarizes the achievements of past which can be extrapolated to characterize the possible array of polymeric interactions, exploiting their desirable properties for future studies.

Chordoma is a rare type of tumor of the skeletal system that can occur anywhere along the spine, from the base of the skull to the tailbone. Chordoma is a slowly growing primary tumor that arise from an intra-osseous remnant of notochordal cells. These neoplasms typically occur in the axial skeleton; the most common location is the sacrococcygeal region followed by skull base and spine. Chordomas typically occur in adults between ages 50 and 70. About five percent of them are diagnosed in children. Males are affected about twice as often as females. Histopathologically, chordomas are divided into conventional (the most common) type, chondroid, and dedifferentiated types. They are mainly locally aggressive with gradual involvement of bone and soft tissues. However, metastases have been reported mainly at late stages. Aggressive initial therapy, based on maximal possible resection followed by postoperative irradiation, improves overall outcome. Up to 40 percent of patients recur after treatment showing a poor prognosis but both radiation and surgery can be used as salvage therapy. Radiation therapy is used in order to treat patients with advanced, residual, inoperable lesions or with local recurrence. Particle therapy (protons and ions) has been reported as a very active form of irradiation for its peculiar physical properties. Chordomas are reported as tumors non sensitive to chemotherapy; molecularly targeted therapies are increasingly used in recent years with promising results but deserve further investigation.

Bronchial asthma is characterized by an eosinophilic inflammatory process in the airways, and manifests itself functionally by bronchial hyperresponsiveness and variable airflow obstruction. In the past this inflammatory process was presumed to be predominantly present in the large and intermediate airways. This is not surprising since functional abnormalities in the small airways (or so-called silent zone) are much more difficult to establish in comparison to changes in the larger airways. As a consequence, changes in airway calibre and bronchial hyperresponsiveness are mainly measured in the central part of the lung, i.e. by means of the FEV1 at rest or after challenge with bronchoconstrictive stimuli like histamine and methacholine. Recently, advanced physiological, radiological and morphological studies have shown that the inflammatory process extends to the peripheral airways and even the alveolar compartment. This so-called peripheral inflammation may be related to the clinical manifestation of the severity of asthma. Targeting the small airways with inhaled corticosteroids (ICS) with a small particle size and a high peripheral deposition may result in better control of the disease in a subset of patients. Indeed, several clinical-mechanistic studies have shown that, in contrast to the ‘conventional’ ICS with ‘large’particles, these extrafine ICS may induce functional and immunologic alterations in the peripheral lung compartment The presence and clinical consequences of peripheral inflammation and its therapeutic consequences are discussed in this review.

Amorphous materials have always been an essential part of pharmaceutical research They are important because of their characteristic solubility characteristics, common occurrence, and physicochemical instability relative to corresponding crystals. Some pharmaceutical agents have a tendency to exist as amorphous solids, while others require prevention of their crystallization to remain in the amorphous state in order to achieve desire characteristics. Amorphous solids can be stabilized by some common pharmaceutical processes like solid dispersion technique, solvent evaporation, milling, lipid dispersion. This article reviews the methodologies and approaches for stabilization of amorphous form.

Renal biopsy was broadly used for research in some institutions of the former Soviet Union: it was performed in patients with amyloidosis, renovascular hypertension (both kidneys), pyelonephritis and chronic alcoholism. When renal biopsy was performed in accordance with clinical indications, a part of the tissue cylinder was sometimes consumed for scientific purposes. Renal biopsy was performed in clinically inactive or latent glomerulonephritis, isolated proteinuria and/or hematuria. Semithin sections, silver and trichrome stains were not used in the routine, while electron microscopy was applied infrequently. In isolated proteinuria and/or hematuria, histologically are often found only minor glomerular abnormalities: slight mesangial widening and hypercellularity, scarce deposits of immunoglobulins and complement. Under such conditions, this picture can be misinterpreted as glomerulonephritis, which can entail overtreatment. In some studies, patients with the inactive or latent glomerulonephritis, isolated proteinuria or hematuria, were treated with corticosteroids and/or cytotoxic drugs. Today, the upturn in Russian economy enables acquisition of modern equipment; and medical research is on the increase. Under these circumstances, the main purpose of this letter was to remind that, performing renal biopsy, the risk-to-benefit ratio should be kept as low as possible.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and forms a multifunctional transducing organ that regulates cardiovascular homeostasis. Disruption of endothelial integrity, as a result of either angioplasty or stent deployment, may produce a late in-stent restenosis and limit the beneficial outcome of reconstructive vascular surgery. Restoration of endothelial lining requires spreading, migration and proliferation of ECs nearby the lesion site. Intracellular Ca2+ signalling plays a major regulatory role in stimulating wound healing, however, the mechanism whereby injury increases Ca2+ levels at the wound edge is still unclear. The analysis of Ca2+ signals elicited by scraping an endothelial monolayer in vitro suggested the involvement of intracellular Ca2+ release from InsP3-sensitive stores and Ca2+ entry through unknown ion channels in the plasma membrane. Recent studies carried out on excised rat aorta highlighted a novel role for connexin hemichannels (CxHcs) in mediating Ca2+ entry in injured endothelium. Understanding the signal transduction pathway leading to EC activation is likely to provide novel targets to design therapeutic applications aiming to restore endothelial integrity and treat cardiovascular diseases. Therefore, alternative drug-eluting stents might be devised to trigger CxHc opening and reduce in-stent restenosis following vascular regenerative surgery.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease arising from monoclonal proliferation of B lymphocytes. In the absence of poor risk features, CLL is characterized by an indolent clinical course but in 2012 it is still considered an incurable malignancy. Treatment of CLL is highly individualized and the majority of patients do not require treatment at the time of diagnosis. Therapy is, however, indicated for patients with advanced stage disease, high tumor burden, severe disease-related "B" symptoms, cytopenias, poor-risk cytogenetic features or repeated infections. Rituximab, a monoclonal antibody that targets the cell-surface molecule CD20 expressed on B-lymphocytes, is not widely used as a mono-therapy for CLL. Commonly employed first-line treatment regimens do include chlorambucil in conjunction with corticosteroids, fludarabine and cyclophosphamide or pentostatin and cyclophosphamide in conjunction with rituximab and, most recently, bendamustine and rituximab. While there have been substantial strides in finding aggressive combination chemo-immunotherapy regimens that have significant activity in the front-line setting, treatment options for patients with relapsed, poor risk, or refractory CLL are limited. Alemtuzumab, a monoclonal antibody targeting CD52 is increasingly becoming a part of the Oncologists’ armamentarium to combat for poor–risk CLL associated with adverse cytogenetic aberrations or recurrent or progressive CLL, but its use has been limited due to concerns for infectious complications. Ofatumumab (Arzerra™) is a novel, fully humanized anti-CD20 monoclonal antibody that binds to both small and large extracellular loops of CD20, has increased complement dependent cytotoxicity (CDC) and antibody dependent cytotoxicity (ADCC) compared to rituximab. Based on the results of a pivotal phase II study (Hx-CD20-406), which showed clinically meaningful and durable overall response rates, Ofatumumab was granted accelerated approval in October 2009 by U.S. Food and Drug administration for treatment of patients with fludarabine and alemtuzumab-refractory CLL. Several randomized trials are underway investigating its clinical benefit in CLL and other non-Hodgkin’s lymphomas.