Biolmpacts
Volume:3 Issue: 2, Jun 2013

It seems solid tumors are developing smart organs with specialized cells creating specified bio-territory, the so called “tumor microenvironment (TME)”, in which there is reciprocal crosstalk among cancer cells, immune system cells and stromal cells. TME as an intricate milieu also consists of cancer stem cells (CSCs) that can resist against chemotherapies. In solid tumors, metabolism and vascularization appears to be aberrant and tumor interstitial fluid (TIF) functions as physiologic barrier. Thus, chemotherapy, immunotherapy and gene therapy often fail to provide cogent clinical outcomes. It looms that it is the time to accept the fact that initiation of cancer could be generation of another form of life that involves a cluster of thousands of genes, while we have failed to observe all aspects of it. Hence, the current treatment modalities need to be re-visited to cover all key aspects of disease using combination therapy based on the condition of patients. Perhaps personalized cluster of genes need to be simultaneously targeted.

Gene therapy has been recently shown as a promising tool for cancer treatment as nanotechnology-based safe and effective delivery methods are developed. Generally, genes are wrapped up in extremely tiny nanoparticles which could be taken up easily by cancer cells, not to their healthy neighboring cells. Several nanoparticle systems have been investigated primarily to address the problems involved in other methods of gene delivery and observed improved anticancer efficacy suggesting that nanomedicine provides novel opportunities to safely deliver genes, thus treat cancer. In this review, various nanoparticle types and related strategies, used in gene delivery for cancer treatment, have been discussed.

Nowadays, using drug delivery is an essential method to improve cancer therapy through decreasing drug toxicity and increasing efficiency of treatment. Silibinin (C25H22O10), a polyphenolic flavonoid which is isolated from the milk thistle plant, has various applications in cancer therapy but it has hydrophobic structure with low water solubility and bioavailability. To increase the effect of silibinin, silibinin-loaded PLGA-PEG-Fe3O4 was prepared to determine the inhibitory effect of this nanodrug on Telomerase gene expression. The rate of silibinin loaded into PLGA-PEG-Fe3O4 was measured. Then, the cytotoxic effect of silibinin-loaded PLGA-PEG-Fe3O4 was determined by Methyl Thiazol Tetrazolium (MTT) assay. After that, inhibition of Telomerase gene expression was indicated through Real-time PCR. Data analysis from MTT assay showed that silibinin-loaded PLGA-PEG-Fe3O4 had dose dependent cytotoxic effect on T47D cell line. MTT assay showed no cytotoxic effect of free PLGA-PEG- Fe3O4 on T47D breast cancer cell line. Real Time PCR analysis showed that the level of telomerase gene expression more efficiently decreased with silibinin-loaded PLGA-PEG- Fe3O4 than with free silibinin alone. The present study indicates that this nanodrug causes down-regulation of Telomerase gene expression in cancer cells. Therefore, PLGA-PEG- Fe3O4 could be an appropriate carrier for hydrophobic agents such as silibinin to improve their action in cancer therapy.

The present investigation was aimed to optimize the formulating process of sirolimus liposomes by thin film hydration method. In this study, a 32 factorial design method was used to investigate the influence of two independent variables in the preparation of sirolimus liposomes. The dipalmitoylphosphatidylcholine (DPPC) /Cholesterol (Chol) and dioleoyl phosphoethanolamine(DOPE) /DPPC molar ratios were selected as the independent variables. Particle size (PS) and Encapsulation Efficiency (EE %) were selected as the dependent variables. To separate the un-encapsulated drug, dialysis method was used. Drug analysis was performed with a validated RP-HPLC method. Using response surface methodology and based on the coefficient values obtained for independent variables in the regression equations, it was clear that the DPPC/Chol molar ratio was the major contributing variable in particle size and EE %. The use of a statistical approach allowed us to see individual and/or interaction effects of influencing parameters in order to obtain liposomes with desired properties and to determine the optimum experimental conditions that lead to the enhancement of characteristics. In the prediction of PS and EE % values, the average percent errors are found to be as 3.59 and 4.09%. This value is sufficiently low to confirm the high predictive power of model. Experimental results show that the observed responses were in close agreement with the predicted values and this demonstrates the reliability of the optimization procedure in prediction of PS and EE % in sirolimus liposomes preparation.

We have recently shown that in high cholesterol-fed rabbits, the sensitivity of epicardial adipose tissue to changes in dietary fat is higher than that of subcutaneous adipose tissue. Although the effects of diabetes on epicardial adipose tissue thickness have been studied, the influence of diabetes on profile of epicardial free fatty acids (FFAs) has not been studied. The aim of this study is to investigate the effect of diabetes on the FFAs composition in serum and in the subcutaneous and epicardial adipose tissues in patients undergoing coronary artery bypass graft (CABG). Forty non-diabetic and twenty eight diabetic patients candidate for CABG with > 75% stenosis participated in this study.Fasting blood sugar (FBS) and lipid profiles were assayed by auto analyzer. Phospholipids and non-estrified FFA of serum and the fatty acids profile of epicardial and subcutaneous adipose tissues were determined using gas chromatography method. In the phospholipid fraction of diabetic patients’ serum, the percentage of 16:0, 18:3n-9, 18:2n-6 and monounsaturated fatty acids (MUFAs) was lower than the corresponding values of the non-diabetics; whereas, 18:0 value was higher. A 100% increase in the amount of 18:0 and 35% decrease in the level of 18:1n-11 was observed in the diabetic patients’ subcutaneous adipose tissue. In epicardial adipose tissue, the increase of 18:0 and conjugated linolenic acid (CLA) and decrease of 18:1n-11, ω3 (20:5n-3) and 22:6n-3 were significant; but, the contents of arachidonic acid and its precursor linoleic acid were not affected by diabetes. The fatty acids’ profile of epicardial and subcutaneous adipose tissues is not equally affected by diabetes. The significant decrease of 16:0 and ω3 fatty acids and increase of trans and conjugated fatty acids in epicardial adipose tissue in the diabetic patients may worsen the formation of atheroma in the related arteries.

Community-acquired pneumonia (CAP) is among the common diseases that causes illness and death world-wide. Limited data is available for the treatment of patients with CAP and/or medical outcome of CAP patients in Pakistan. This cross-sectional and prospective study was done to determine etiology of CAP patients and to evaluate the therapeutic effects of antibiotics commonly used in treating CAP patients in two different inner-city hospitals, Pakistan. The study was conducted on 200 hospitalized patients presenting clinical and radiographic evidences of CAP. The patients were assessed for the causative pathogen and their prescriptions were analyzed for the management and treatment of CAP and associated symptoms of pneumonia. Finally the medical outcomes were evaluated. On establishing the microbial etiology of pneumonia among different CAP causing pathogens, K. pneumoniae was found to be the most identified causative agent (30%) followed by S. pneumoniae (23%). Majority of the patients received cephalosporin antibiotics (80%) followed by aminoglycosides (65%) and penicillins (50%) either as monotherapy or combination treatment. Therapeutic success was observed to occur in majority of the patients. The recovery of CAP patients occurred probably because they received antibiotics which are recommended by WHO and American Thoracic Society. Another reason for successful therapeutic outcome was found to be the significant patient compliance for treatment. There is a great need for such types of investigational studies to be conducted in developing countries which may guide the empirical therapy and help in defining proper treatment guidelines.

Amphiphilic copolymers are capable of forming core shell-like structures at the critical micellar concentration (CMC); hence, they can serve as drug carriers. Thus, in the present work, polymeric micelles based on novel chitosan derivative were synthesized. Block copolymer of palmitoyl glycol chitosan sulfate (PGCS) was prepared by grafting palmitoyl and sulfate groups serving as hydrophobic and hydrophilic fractions, respectively. Then, fourier transform infrared spectra (FTIR) and spectral changes in iodine/iodide mixture were carried out. FTIR studies confirmed the formation of palmitoyl glycol chitosan sulfate (PGCS) and spectral changes in iodine/iodide mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. Therefore, our study indicated that polymeric micelles based on palmitoyl glycol chitosan sulphate could be used as a prospective carrier for water insoluble drugs.

Ischemia/Reperfusion (IR) injury mainly causes the increase of enzymes involved in myocytes injury including CK-MB (creatine kinase-MB) isoenzyme and LDH (lactate dehydrogenase). Leakage of CK-MB isoenzyme and LDH from myocardial tissues to blood is indicator of acute myocardial infarction. The aim of this study was to assess the effect of HEMADO on IR injury and its relationship with mitochondrial ATP-sensitive K+ channels (mitoKATP) in rat heart. Twenty eight male Wistar rats (250-300g) were divided into four groups (seven members in each group): control (without ischemia), I/R (with ischemia+without HEMADO), ischemia received HEMADO (HEMADO), ischemia received HEMADO and 5-HD (5-hydroxydecanoate, specific mitoKATP channel blocker) (HEMADO+5-HD). The animals were anesthetized and the hearts were quickly removed and mounted on Langendorff apparatus and perfused by Krebs-Henseleit solution under constant pressure and temperature of 37ºC. After 20 minutes of stabilization, ischemic groups were exposed to 40 minutes of global ischemia and consecutive 90 minutes of reperfusion. IR injury increased the level of LDH and CK-MB in the collected coronary flow during 5 minutes since start of reperfusion. HEMADO reduced the enzymes’ levels and using 5-HD abolished the effect of HEMADO. Our findings indicated that HEMADO could protect the heart against ischemia-reperfusion injury by decreasing the CK-MB and LDH levels. The cardioprotective effect of HEMADO may be mediated in part by mitoKATP.