Nanopharmaceuticals: A Boon to the Brain-Targeted Drug Delivery

Brain is well known for its multifarious nature and complicated diseases. Brain consists of natural barriers that pose difficulty for the therapeutic agents to reach the brain tissues. Blood-brain barrier is the major barrier while blood-brain tumor barrier, blood-cerebrospinal (CSF) barrier and efflux pump impart additional hindrance. Therapeutic goal is to achieve a considerable drug concentration in the brain tissues in order to obtain desired therapeutic outcomes. To overcome the barriers, nanotechnology was employed in the field of drug delivery and brain targeting. Nanopharmaceuticals are rapidly emerging sub-branch that deals with the drug-loaded nanocarriers or nanomaterials that have unique physicochemical properties and minute size range for penetrating the CNS. Additionally, nanopharmaceuticals can be tailored with functional modalities to achieve active targeting to the brain tissues. The magic behind their therapeutic success is the reduced amount of dose and lesser toxicity, whereby localizing the therapeutic agent to the specific site. Different types of nanopharmaceuticals like polymeric, lipidic and amphiphilic nanocarriers were administered into the living organisms by exploiting different routes for improved targeted therapy. Therefore, it is essential to throw light on the properties, mechanism and delivery route of the major nanopharmaceuticals that are employed for the brain-specific drug delivery

HOW ADVERTISING INFLUENCES YOUR CHOICES AND PURCHASING BEHAVIOUR WHILE SELECTING TOOTHPASTE

From television to wall murals, advertising is digital, ubiquitous and a powerful force shaping attitudes and behaviour in today's world. Owing to the rising consumer demands across products and services; the upsurge in competition across markets and companies vying for larger market share, advertisements, more precisely manipulative advertisements have become prevalent and the only means of generating revenues for companies that influence in ways we don't even realise.Keywords: Advertising, Purchasing, Advertising Standards Authority, Toothpast

A call for action to the biomaterial community to tackle antimicrobial resistance

The global surge of antimicrobial resistance (AMR) is a major concern for public health and proving to be a key challenge in modern disease treatment, requiring action plans at all levels. Microorganisms regularly and rapidly acquire resistance to antibiotic treatments and new drugs are continuously required. However, the inherent cost and risk to develop such molecules has resulted in a drying of the pipeline with very few compounds currently in development. Over the last two decades, efforts have been made to tackle the main sources of AMR. Nevertheless, these require the involvement of large governmental bodies, further increasing the complexity of the problem. As a group with a long innovation history, the biomaterials community is perfectly situated to push forward novel antimicrobial technologies to combat AMR. Although this involvement has been felt, it is necessary to ensure that the field offers a united front with special focus in areas that will facilitate the development and implementation of such systems. This paper reviews state of the art biomaterials strategies striving to limit AMR. Promising broad-spectrum antimicrobials and device modifications are showcased through two case studies for different applications, namely topical and implantables, demonstrating the potential for a highly efficacious physical and chemical approach. Finally, a critical review on barriers and limitations of these methods has been developed to provide a list of short and long-term focus areas in order to ensure the full potential of the biomaterials community is directed to helping tackle the AMR pandemic

High Altitude Cerebral Edema with concomittent rhabdomyolysis: A rare presentation

We report the case of a young gentleman who developed High Altitude Cerebral Edema (HACE) along with rhabdomyolysis whilst on a trip to the northern areas of Pakistan. High Altitude Cerebral Edema (HACE) represents a serious and potentially fatal type of Acute Mountain sickness (AMS). Rhabdomyolysis presenting with HACE is uncommon however cases have been reported. In our patient, clinical presentation with severe bilateral lower limb pain and difficulty walking along with the increased agitation and confusion made it difficult to recognize; however early descent and management allowed for good recovery. MRI findings with microhemorrhages as found in our patient are increasingly being recognized in HACE with improving sensitivity of available imaging modalities. This case highlights the diverse clinical presentations that can exist with HACE and hence the need for medical professionals to maintain a high index of suspicion in anyone with a recent ascent to high altitude regions who develop neurological manifestations

Accidental finding of odontoma during routine chronic periodontitis therapy-a rare finding

Chronic periodontitis is an infectious disease resulting in inflammation within supporting tissues of the teeth, progressive attachment loss and bone loss”. Odontomas are the most common type of odontogenic tumors and generally they are asymptomatic. This paper describes an accidental finding of odontoma in an adult patient of generalized chronic periodontitis. Surgical excision of the lesion was performed .Reporting of such cases is necessary as initially there was no clinical or radiographic evidence of lesion was present .Dentist should well equipped and prepared for incorporation any modification during flap surgery of for successful management and better patient care

Cabazitaxel-Loaded Nanocarriers for Cancer Therapy with Reduced Side Effects

Jevtana® is a micellar cabazitaxel (CBZ) solution that was approved for prostate cancer in 2010, and recently, this drug has been reported for breast cancer. The purpose of this study is to evaluate the mediated delivery of CBZ via liposomes and nanoparticles (NPs) for the treatment of breast cancer and compare these with a micellar formulation that is currently in clinical use. CBZ-loaded nanocarriers were prepared with particle sizes between 70–110 nm, and with the sustained in vitro release of CBZ for more than 28 days. Cytotoxicity studies on MCF-7 and MDA-MB-231 cells demonstrated the toxic potential of these nanocarriers. Cellular internalization revealed that NPs and liposomes have better permeability than micelles. Cell cycle analysis and apoptosis studies on MCF-7 and MDA-MB-231 cells confirmed G2/M phase arrest as well as cell death due to apoptosis and necrosis, where formulations were found to be effective compared to a micellar CBZ solution. Results from pharmacokinetic studies revealed that there is an increased circulation half-life and mean residence time for CBZ liposomes and NPs in comparison with a micellar CBZ solution. CBZ liposomes and NPs showed a reduction in hemolysis and neutropenia in comparison with a micellar CBZ solution in rats

Dendrimer mediated targeting of siRNA against polo‐like kinase for the treatment of triple negative breast cancer

International audienceIrresponsiveness of triple negative breast cancer (TNBC) toward conventional therapies has drawn attention toward siRNA therapeutics. In gene delivery, dendrimers are gaining significant attention due to their characteristic features and polo-like kinase (PLK1) is reported as a potential target for TNBC. In this work, phosphorus and polyamidoamine dendrimer (generation 3 and 4 of each type) are explored to address delivery challenges of PLK1 siRNA (siPLK1). Dendriplexes were formed and complexation was found at 3:1 N/P ratio for all dendrimers by gel electrophoresis. Complexation was also supported by zeta potential, circular dichroism and intercalation assay. Dendriplexes were found to be stable in presence of ribonuclease and serum. Dendriplexes resulted in enhanced cell uptake of siPLK1 compared to siPLK1 solution in MDA-MB-231 and MCF-7 cells. Dendriplexes caused increased cell arrest in sub-G1 phase compared to solution. These observations suggested phosphorus and polyamidoamine dendrimers as potential carriers for siPLK1 delivery to treat TNBC

Fabrication and optimization of pH-sensitive mannose-anchored nano-vehicle as a promising approach for macrophage uptake

Mannose receptors (MR) are highly over-expressed on macrophages in the inflammatory bowel disease (IBD) and can be targeted by developing mannose-anchored nano-carrier system. In this study, mannosylated chitosan (MC) polymer was synthesized because of its high affinity for mannose receptors. Afterward, MC nanoparticles (NPs) were fabricated encapsulating dexamethasone to target macrophages for attenuation of inflammation at initial stages. Further, NPs were coated with a pH-sensitive polymer to control the premature drug release in the stomach. NPs were optimized using a surface response quadratic model to study the impact of various process parameters. Optimized NPs were then characterized for size, morphology, zeta potential, surface chemistry, biocompatibility, and uptake by macrophages. The average particle size was found to be 380 +/- 19.8 nm with an encapsulation efficiency of 78.1 +/- 1.17%. pH-dependent drug release profile was obtained with an average release of 73.9 +/- 5.24% over 72 h in simulated intestinal fluid (pH 7.4). Moreover, the NPs uptake by the macrophages supported the viability of macrophages with the NPs and did not show any adverse effects. Moreover, this study was supported by the uptake of NPs inside macrophages. Altogether, the data supported that MC NPs could serve as a potential anti-inflammatory therapeutic approach to target macrophages in IBD