Mohammad Anwar

Cancer targeted metallic nanoparticle: targeting overview, recent advancement and toxicity concern.

The targeted delivery of theranostic agents to the cancer cells is one of the major challenges and an active field of research in the development of cancer chemotherapeutic approaches. Theranostic metallic nanoparticles (TMNPs) have garnered increasing attention in recent years as a novel tool for theranostic application such as imaging, diagnosis, and therapeutic delivery of active agents to tumour specific cells. This paper attempts to unveil the multidimensional theranostic aspects of multifunctional metallic nanoparticles (MNPs)including passive and active targeting (HER2, Folate, Angiogenesis etc.) as well as the RES escaping approach. Special attention is given to the theranostic application of MNPs in oncology. Patents issued by the US office in this nanotechnological arena are also included emphasising the importance of MNPs in current cancer treatment/imaging research scenario. Keeping in mind the blooming research in clinical application directed nanotechnology; toxicity concerns related with MNPs are. also discussed, in element.

In vitro and in vivo evaluation of Assam Bora rice starch-based bioadhesive microsphere as a drug carrier for colon targeting.

Objective: The aim of this study is to develop, characterize and evaluate (in vitro and in vivo) a novel colon-targeted bioadhesive microsphere (BAM) containing metronidazole (MTZ). Methods: BAMs are prepared using Assam Bora rice starch as a natural bioadhesive polymer by a double emulsion solvent evaporation method. Results: The prepared microspheres showed a uniform spherical shape, with excellent retention time. The in vitro drug release study of the optimized formulations, in different physiological environments, confirmed the insignificant release of metronidazole in the physiological conditions of the stomach (10 – 12.5%) and small intestine (< 25%). Further, fast and major drug release in cecal content (> 90) indicated that the release of the drug was unaffected by the hostile environment of the gastrointestinal tract (GIT). In vitro bacterial inhibition studies illustrated that MTZ loaded BAMs, inhibiting metronidazole-sensitive Bacteroides fragilis and selected BAMs (F1 – F7), have an equivalent or higher zone of inhibition than the marketed formulation. An in vivo organ distribution study of MTZ revealed that Assam Bora rice starch-based microspheres were relatively intact in the upper part of GIT, and the drug was released only after reaching the colon, owing to the microbial degradation of Assam Bora rice starch by microflora residing in the colon. Conclusion: MTZ release patterns exhibited slow and extended release over longer periods of time, which shows the potential of Assam Bora rice starch microspheres as a drug carrier for an effective colon-targeted delivery system.

Development of Polysaccharide based Colon Targeted Drug Delivery System: Design and Evaluation of Assam Bora rice Starch based Matrix Tablet

The aim of this study was to develop a novel colon targeted matrix tablet containing Metronidazole (MTZ) as model drug. Matrix tablets were prepared using Assam Bora rice starch, which is essentially a natural polymer, by wet granulation technique. The granules prepared were subjected to evaluation for angle of repose, bulk density, compressibility index, Hausners ratio, total porosity, and drug content. The developed tablets were also analysed for thickness, diameter, weight variation tests, tablet crushing strength, friability, and in vitro release studies. The granules displayed satisfactory flow properties, compressibility, Hausners ratio and drug content. Almost all the tablet formulations showed acceptable pharmacotechnical properties and complied with the in-house developed specifications for the tested parameters. Drug release study confirmed to the initial fast release in the acidic environment of surface adhered drug followed by slow release in alkaline media subsequently leading to fast and major drug release in the caecal content. Furthermore, the release of drug was unaffected by the hostile environment of GIT which can be ascribed to microbial degradation, promptly followed by enzymatic degradation. Curve fitting proved that the drug release from the tablets followed the Higuchi model. In vitro bacterial inhibition studies illustrated that the released drugs were able to diffuse through agar medium, inhibiting MTZ sensitive Bacteroides fragilis. The selected MTZ matrix tablets (F1-F6) had zones of inhibition paralleling those of the marketed formulation.

Comparison of antibacterial activity of Ag nanoparticles synthesized from leaf extract of Parthenium hystrophorus L in aqueous media and Gentamicin sulphate: in-vitro

Abstract Monodisperse silver (Ag) nanoparticles were synthesized by using Parthenium hystrophorus L leaf extract in aqueous media. The synthesized nanoparticles were characterized by using UV-vis spectrophotometer, X-ray diffracto-meter (XRD), transmission electron microscope (TEM), and dynamics light scattering (DLS). Size-dependent antibacterial activities of Ag nanoparticles were tested against Gram negative Pseudomonas aeruginosa and Gram positive Staphylococcus aureus. Ag nanoparticles having 20 ± 2 nm size in diameter show maximum zone of inhibition (23 ± 2.2 mm) in comparison to 40 nm and 70 nm diameter nanoparticles for Pseudomonas aeruginosa. The zone of inhibition against Staphylococcus aureus were 19 ± 1.8 mm, 15 ± 1.5 mm and 11 ± 1 mm for 20 nm, 40 nm, and 70 nm, respectively. In addition, affect of concentration of 20 nm size Ag nanoparticles on Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus species were also reported and results were compared with 10 µg/ml dose of Gentamicin sulphate. The Parthenium hystrophorus L leaf extract capped 20 ± 2 nm Ag nanoparticles (7.5 µg/ml) shows statistically significant antibacterial activity than Gentamicin sulphate (10 µg/ml) against Staphylococcus aureus.

Development of Polymeric Nanopaclitaxel and Comparison with Free Paclitaxel for Effects on Cell Proliferation of MCF-7 and B16F0 Carcinoma Cells

Paclitaxel is hydrophobic in nature and is recognized as a highly toxic anticancer drug, showing adverse effects in normal body sites. In this study, we developed a polymeric nano drug carrier for safe delivery of the paclitaxel to the cancer that releases the drug in a sustained manner and reduces side effects. N-isopropylacrylamide/ vinyl pyrrolidone (NIPAAm/VP) nanoparticles were synthesized by radical polymerization. Physico- chemical characterization of the polymeric nanoparticles was conducted using dynamic light scattering, transmission electron microscopy, scanning electron microscopy and nuclear magnetic resonance, which confirmed polymerization of formulated nanoparticles. Drug release was assessed using a spectrophotometer and cell viability assays were carried out on the MCF-7 breast cancer and B16F0 skin cancer cell lines. NIPAAm/ VP nanoparticles demonstrated a size distribution in the 65-108 nm range and surface charge measured -15.4 mV. SEM showed the nanoparticles to be spherical in shape with a slow drug release of ~70% in PBS at 38° over 96 h. Drug loaded nanoparticles were associated with increased viability of MCF-7 and B16F0 cells in comparison to free paclitaxel. Nano loaded paclitaxel shows high therapeutic efficiency by sustained release action for the longer period of time, i increasing its efficacy and biocompatibility for human cancer therapy. Therefore, paclitaxel loaded (NIPAAm/VP) nanoparticles may provide opportunities to expand delivery of the drug for clinical selection.

Feasibility of Assam Bora Rice Starch as a Compression Coat of 5-Fluorouracil Core Tablet for Colorectal Cancer

The colon and rectum are the parts of digestive system of human beings. Cancer affecting either of these organs may be called colorectal cancers. Conventional cancer chemotherapy is not very effective for treatment of colorectal cancer, as the drug molecule does not reach the target site at therapeutic concentration, on the other side they produces sever systemic toxic effect. Aim of this study was to develop a novel colon targeted Assam Bora rice starch compression coated tablet for site specific delivery of 5-FU to the colon without the drug being released in stomach or small intestine. Core tablet of 5-FU was prepared using microcrystalline cellulose (MCC) and spray dried lactose by direct compression method. The in vitro drug release study in different physiological environment confirmed insignificant release of 5-FU in physiological condition of stomach and small intestine further fast and major drug release in caecal content. In vivo drug absorption of optimized formulation was performed in order to establish its targeting potential in colon. It is concluded from the present study that Assam Bora rice starch can be used as a drug carrier for an effective colon targeted delivery system for drugs effective against the large intestine resident disease condition.

Application of Decoy Oligonucleotides as Novel Therapeutic Strategy: A Contemporary Overview

Molecular therapy is emerging as a potential strategy for the treatment of many diseases. Correct regulation of gene expression is essential for both, to normal development and proper functioning of the all the organisms. Even after four decades of intensive research, it is still a major problem from regulatory and technical point of view, to replace defective genes. The technology of decoy oligonucleotides has received considerable attention to treat and cure a variety of diseases and abnormal physiological conditions, because they provide a rational way to design and selective regulation of a specific gene expression. Decoy oligonucleotides are widely used as inhibitors of specific gene expression because they can offer exciting possibility of expression and blocking of a particular gene without any changes in the functions of other genes. Advances in the decoy oligonucleotides are rapidly paving the way to new insights into the origin and treatment of inflammatory, cancer and/or other immune disorders. The review covers the progress achieved towards the development of decoy oligonucleotides as a potential strategy in a new class of molecular therapy.

Role of Nanomedicines in Delivery of Anti-Acetylcholinesterase Compounds to the Brain in Alzheimer’s Disease

Alzheimers disease (AD) is a multifarious progressive neuro-degenerative state among elders. Potentiation of central cholinergic activity by using acetylcholinesterase inhibitors (AChEI) is considered as one of the major pharmacological means for the management of AD. Investigation in the past and the rest decades revealed that many drugs with anti-AD activity, including the AChEI have been discovered from natural and synthetic origin but getting success in their brain delivery is still limited. However, barriers like blood-brain barrier, blood-cerebrospinal fluid barrier and p-glycoproteins restrict the effective and safe drug delivery to the brain in patients with AD. Advancement in nanotechnology-based drug delivery systems over the last decade exemplifies the effective drug delivery and targeting to the brain with controlled rate in various diseases including AD. Till recently, diverse kinds of nanomedicines for targeting of the anti-AD drugs in brain are being studied. In this review, we have highlighted the recent progress in AChEI, challenges in their effective brain delivery (physicochemical properties and biological barriers) and possible nanotechnology-based strategies that can deliver drugs across the CNS barriers during AD.

Chromatographic separation of piracetam and its metabolite in a mixture of microsomal preparations, followed by an MS/MS analysis.

A rapid bioanalytical method was evaluated for the simultaneous determination of piracetam and its metabolite (M1) in human microsomal preparations by fast ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). In addition, a validated method of M1 in rat plasma was developed and successfully applied on pharmacokinetic studies. The present study was carried out to determine the metabolic pathways of piracetam for phase I metabolism and used cytochrome P450 isoforms responsible for the piracetam metabolism in human liver microsomes (HLMs). While additional potential metabolites of piracetam were suggested by computer-modeling. The resulting 2-(2-oxopyrrolidin-1-yl) acetic acid was the sole metabolite detected after the microsomal treatment. The amide hydrolysis mainly underwent to form a metabolite i.e., 2-(2-oxopyrrolidin-1-yl) acetic acid (M1).

Size- and shape-dependent clinical and mycological efficacy of silver nanoparticles on dandruff

Dandruff is a prominent scalp problem caused by the growth of fungus Malassezia furfur, potentially cascading into dermal inflammation, itching, and tissue damage. The present work outlines a detailed analysis of the treatment of scalp infection using silver nanomaterials (Ag NMs), and focuses on biocidal activity owing to manipulation of size, shape, and structure. Monodisperse silver spherical nanoparticles (NPs) and nanorods (NRs) were synthesized by chemical routes that were characterized using analytical and spectroscopic techniques. Ag NMs demonstrated enhanced biocidal tendencies compared to market available drugs, itracanozole and ketoconazole, showing greater zones of inhibition. The obtained 20 nm and 50 nm spherical-shaped NPs and 50 nm NRs showed concentration-, size-, and shape-dependent antifungal activity, with 20 nm spherical-shaped NPs exhibiting excellent potency. Minimum inhibitory concentration for 20 nm was lowest at 0.2 mg/mL in comparison to 0.3 mg/mL for NRs. Primary irritation index was 0.33 and 0.16 for 20 nm and 50 nm spherical-shaped NPs, respectively, while 50 nm rod-shaped NMs exhibited negligible redness. An in vivo model for M. furfur infection was generated by passing fungi subcutaneously in rats’ skin. Again, 20 nm particles showed best normalization of skin after 10 days on regular dosing, in comparison with bigger and rod-shaped particles. The statistical clinical score was highest for Ag nanorods, followed by 50 nm Ag NPs-treated animals. It was observed that 20 nm spherical particles exhibited the lowest score (0) compared with others as well as with antifungal drugs. Biochemical analysis performed by checking antioxidant enzymatic activities indicated tissue repair and normalization of enzymes and protein concentration by Ag NPs.