Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments

Cancer is caused by an uncontrolled cell division, forming a tumor capable of metastasis. Cancer is the second leading cause of death worldwide. Conventional treatments kill healthy cells, causing side effects. Recently, nanomaterials are explored due to properties such as as- nano-size, high loading, and ligands’ attachment for a selective delivery. Apart from normal body cells, cancer cells express many receptors in excess, which serve as ‘targets’ for attacking the cells. Various ligands like proteins, peptides, polysaccharides can be attached to nanoparticles to allow proper and specific reach to the tumor. Such nanoparticles go to their desired site and stick onto the receptors, taken inside the cells by various methods. Antibodies are natural proteins that bind to foreign substances and remove them. IgG being the most explored antibody, suffers from many disadvantages such as non-specificity for required antigen, limited binding sites, low tumor penetration. Hence many researchers experimented by removing and adjusting the binding sites, using only the binding sites, enhancing the valency of naturally available IgG. It gave many benefits such as enhanced penetration, reduced immunogenicity, better delivery of drugs with fewer side effects. Continuing advancements in the field of protein engineering will help scientists to come up with better solutions. The properties allow easy surface interaction and entry, achieve better biodistribution, and reduce the amount of drug required. Targeting is based on Paul Ehrlich’s ‘magic bullet, ‘where the therapeutic moiety has two parts-one to identify the target and the second to eliminate it. This concept is revised to incorporate a third component, a carrier. Many nanocarriers can be used to target cancer cells containing ligands to identify malignant cells. Approaches to targeting are passive, active and physical targeting. Many such nanoparticles are in clinical trials and can be a better solution to cancer therapy

Treatment of irritable bowel syndrome with diarrhoea using titrated ondansetron (TRITON): study protocol for a randomised controlled trial

Background: Irritable bowel syndrome with diarrhoea (IBS-D) affects up to 4% of the general population. Symptoms include frequent, loose, or watery stools with associated urgency, resulting in marked reduction of quality of life and loss of work productivity. Ondansetron, a 5HT3 receptor antagonist, has had an excellent safety record for over 20 years as an antiemetic, yet is not widely used in the treatment of IBS-D. It has, however, been shown to slow colonic transit and in a small randomised, placebo-controlled, cross-over pilot study, benefited patients with IBS-D. Methods: This trial is a phase III, parallel group, randomised, double-blind, multi-centre, placebo-controlled trial, with embedded mechanistic studies. Participants (n = 400) meeting Rome IV criteria for IBS-D will be recruited from outpatient and primary care clinics and by social media to receive either ondansetron (dose titrated up to 24 mg daily) or placebo for 12 weeks. Throughout the trial, participants will record their worst abdominal pain, worst urgency, stool frequency, and stool consistency on a daily basis. The primary endpoint is the proportion of “responders” in each group, using Food and Drug Administration (FDA) recommendations. Secondary endpoints include pain intensity, stool consistency, frequency, and urgency. Mood and quality of life will also be assessed. Mechanistic assessments will include whole gut transit, faecal tryptase and faecal bile acid concentrations at baseline and between weeks 8 and 11. A subgroup of participants will also undergo assessment of sensitivity (n = 80) using the barostat, and/or high-resolution colonic manometry (n = 40) to assess motor patterns in the left colon and the impact of ondansetron. Discussion: The TRITON trial aims to assess the effect of ondansetron across multiple centres. By defining ondansetron’s mechanisms of action we hope to better identify patients with IBS-D who are likely to respond

Recent Pharmaceutical Developments in the Treatment of Cancer Using Nanosponges

Nanosponges are a class of nanoparticles characterized by their sponge-like surface that ensures high loading capacity. Cancer causes high mortality and requires precise treatment without harming the body. Hence, nanoparticles are required to target medications to tumor. Nanosponges may be synthesized from various polymers and metals, giving them distinct properties. The majority of polymer synthesis entails crosslinking, while metal synthesis entails the isolation of metal nanoparticles accompanied by their assembly into sponges. Nanosponges must be functionalized to precisely attack tumors. There are several patents on nanosponges synthesis and their use. Future trends in the usage of nanosponges include simultaneous distribution of several molecules and expanding the spectrum of use from medicinal delivery to substance encapsulation for a multitude of applications. As their usage in the pharmaceutical industry grows, more emphasis should be put on toxicity-related aspects induced by the near association of cell membrane and nanosponge resulting in intracellular dissolution or reactive oxygen species (ROS) generation, which in turn damages various cellular components. Many techniques have been created to reduce toxicity, including functionalization with various materials such as antioxidants, polymers and altering nanosponges composition. As the application of nanosponges increases in many industries, the phenomenon related to toxicity must be further explored through research

Paralleling technique for frenectomy and oral hygiene evaluation after frenectomy

Background: High frenum attachment is a very common problem in the population. Various conventional techniques are available which has certain disadvantages; in addition to that high frenum also hinders oral hygiene maintenance. This study aims to evaluate patient's response to two different frenectomy technique, and oral hygiene maintenance before and after frenectomy. Materials and Methods: Twenty patients with high labial frenum were randomly selected from the outpatient department. Patients were divided into two groups according to the technique used. Each group contained ten patients. One group was treated by “conventional scalpel technique” and other group by “new paralleling technique”. To evaluate patients response, visual analogue scale for pain and speech were taken at first postoperative day, 1-week and 1-month. In other part of the study the oral hygiene maintenance was evaluated by using plaque and gingival bleeding index at baseline before frenectomy, 1-week and 1-month after frenectomy. Results: Results showed that new paralleling technique for frenectomy causes less postoperative discomfort and also there was significant improvement in the oral hygiene maintenance by the patient after frenectomy. Conclusion: High maxillary frenum causes hindrance in oral hygiene maintenance. Paralleling technique for frenectomy causes less discomfort to the patient during healing phase when compared with the conventional technique