“More than 40 years after the war on cancer was declared, we have spent billions fighting the good fight. The National Cancer Institute has spent some $90 billion on research and treatment during that time. "Some 260 nonprofit organisations in the United States have dedicated themselves to cancer — more than the number established for heart disease, AIDS, Alzheimer’s disease, and stroke combined. Together, these 260 organisations have budgets that top $2.2 billion.” (Dr Margaret Cuomo, A World Without Cancer)
A large proportion of people donate to the world’s cancer research movement either directly or by running sponsored marathons, holding charity bake sales, charity shopping or by countless other indirect donation routes. However, the average donor gives their money with full trust to cancer research charities that it will be spent wisely. Charities publish their annual expenditure breakdown, but unless a donor regularly reads research articles, it can be difficult to understand the specifics of cancer research.
This blog post gives several examples of recent cancer research from around the world, and the role that Texture Analysis has to play.
Microneedles
Much of the role of Texture Analysis in cancer research involves the development of drug delivery systems, due to their need for precise physicochemical properties. Drug delivery is the method of delivering drugs to their site of action within the body, with the goal of achieving a therapeutic outcome. Microneedle research is a common application of Texture Analysis. Microneedles are microscopic applicators used to deliver drugs across the skin and other barriers with benefits compared to traditional hypodermic needles, such as the possibility for controlled drug release.
Researchers from the University of Greenwich have been investigating 3D printed microneedles for anticancer therapy of skin tumours. Arrays were fabricated via stereolithography using a biocompatible resin, with a design that allowed high drug delivery through the skin. Inkjet printing technology was used to deposit anticancer drugs on 3D printed microneedles for rapid release.
The printability of these samples was discussed, and they used their TA.HDplus along with coherence tomography analysis to measure skin piercing capacity. In vivo pre-clinical trials demonstrated high anticancer activity and tumour regression. Read more
Mucoadhesion
Over the past few decades, mucosal drug delivery has received a large amount of attention. Mucoadhesive dosage forms may be designed to enable prolonged retention at the site of application, providing a controlled rate of drug release where necessary. Additionally, the application of dosage forms to mucosal surfaces can be particularly useful for drug molecules not amenable to the oral route.
Scientists from the University of Campinas have been investigating hyaluronic acid in the intestinal tract, including its influence on structure, rheology and mucoadhesion on the intestinal uptake in rats. Oral hyaluronic acid (HA) is a ubiquitous biopolymer that has gained attention as a treatment for local or systemic diseases. Structures were prepared and characterised of free HA with a high, intermediate and low average molar mass; nanoparticles crosslinked with adipic dihydrazide; and mixed formulations.
They used their TA.XTplus Texture Analyser to investigate the mucoadhesive properties of the different HA formulations. The study concluded that certain formulations are promising for targeting other tissues, while others are better for treating dysbiosis. Find out more
Over at the University of Reading, scientists have been researching chitosan/β-glycerophosphate in situ gelling mucoadhesive systems for intravesical delivery of mitomycin-C. The development of mucoadhesive in situ gelling formulations for intravesical application may improve the therapeutic outcomes of bladder cancer patients. In this work, chitosan/β-glycerophosphate (CHIGP) thermosensitive formulations were prepared using three different chitosan grades. Their ability to form in situ gelling systems triggered by changes in temperature upon administration to the urinary bladder were evaluated using vial inversion and rheological methods.
They used their TA.XTplus Texture Analyser to study mucoadhesive properties as well as syringeability through the urethral catheter. The retention of CHIGP formulations, with fluorescein sodium as the model drug, was studied on porcine urinary bladder mucosa ex vivo using the flow-through technique and fluorescent microscopy. CHIGP formulations containing mitomycin-C were prepared and drug release was studied using in vitro dialysis.
It was established that the molecular weight of chitosan influenced the thermogelling, mucoadhesive and drug release behaviour of the in situ gelling delivery systems. Formulations prepared from chitosan with greatest molecular weight were found to be the most promising for intravesical application due to their superior gelling properties and in vitro retention in the bladder. Read more
A researcher from the same group in Reading researched more widely novel mucoadhesive chitosan based formulations for drug delivery to the urinary bladder for their PhD thesis. The intravesical route was chosen as the exemplar transmucosal mode of drug delivery due to the limited therapeutic efficiency of conventional bladder cancer formulations. Drug carriers with improved mucoadhesive properties may prolong drug residence in the bladder.
They used their TA.XTplus Texture Analyser to evaluate the ability of the chitosan or CHIGP solution to pass through a catheter via a syringe. These excipients were found suitable for use in formulating affordable transmucosal dosage forms with superior mucoadhesiveness for a variety of biomedical applications. Find out more
Medicated Chewing Gum for Head and Neck Cancers
Researchers from the University of Louisiana at Monroe have been investigating mechanical characterisation and dissolution of chewing gum tablets (CGTs) containing compressed Health in Gum® and Curcumin/Cyclodextrin Inclusion Complex. Curcumin chewing gums could be therapeutically beneficial if used by the head and neck cancer patients. However, high curcumin loading in chewing gums is needed to achieve the desired therapeutic effect. Preparing gums with high drug load is nonetheless challenging because of the negative impact of solids on their masticatory properties. The use of liquid flavours was found to partially solve this problem.
The objectives of this study were to (1) determine the maximum amount of curcumin that can be loaded into co-compressed chewing gums made from Health in Gum® as the base and flavoured with 1.5% peppermint oil, (2) determine if the addition of sweeteners can improve the yield strength and compressibility of the gums when examined by a TA.XTplus Texture Analyser, (3) examine the effect of temperature over a storage period of one month on the physical stability of the chewing gums, and (4) study the impact of substituting curcumin with its inclusion complex with SBE-β-CD on drug release.
It was found that when flavoured, Health in Gum® could load up to 25% curcumin by weight without compromising its masticatory properties. This study demonstrated how modulating gum composition and storage conditions can impact the mechanical properties of chewing gums with high solids content. Find out more
Dermal Application of Drugs for Skin Cancer
Ethosomes are a novel carrier system used for the delivery of drugs that have a low penetration through the skin and other body barriers. They are soft vesicles made up of Phospholipids, Ethanol and water. Because of their unique structure, ethosomes can efficiently encapsulate and deliver highly lipophilic molecules and hydrophilic drugs into the skin. For this reason, they are particularly suitable drug carriers for skin-related diseases, such as skin cancer.
Researchers from Jamia Hamdard have been investigating fisetin loaded binary ethosomes for management of skin cancer by dermal application on UV exposed mice. Fisetin loaded binary ethosomes were prepared and optimised using Box-Behnken design for dermal application to alleviate skin cancer. The prepared formulations were evaluated for vesicle size, entrapment efficiency and flux of fisetin. Additionally, the optimised formulation was further evaluated by transmission electron microscopy, confocal laser microscopy, vesicles-skin interaction, dermatokinetic study and DPPH (2, 2-diphenyl-1-picryl-hydrazyl) assay.
They used their TA.XTplus Texture Analyser to measure gel texture. The in vivo study was carried out for the evaluation of tumour incidence, pro-inflammatory cytokines such as TNF-α and IL-1α, lipid peroxidation values, glutathione content and catalase activity in mice. The novelty of the work lies in successful optimisation of formulation using Box-Behnken design and characterisation of binary ethosomes carrier of fisetin and demonstration of improved dermal delivery of the same.
The overall data suggest that the fisetin loaded binary ethosomes formulation is a potential dermal delivery system for the management of skin cancer. Find out more
3D Cancer Models
Modelling the behaviour of tumours can help with the understanding of cancer initiation, growth, and migration, and the key role of the tumour microenvironment on these processes. Cancer research has considerably progressed with the improvement of in vitro study models.
Researchers from the University of Stavanger have been modelling 3D cancer growth and extracellular matrix properties in vitro. Cancer can be defined as loss of normal behaviour of cellular components, losing tissue organisation and giving rise to a tumour microenvironment (TME). Increased matrix stiffness, strain and elevated interstitial fluid flow and/or pressure of the extracellular matrix (ECM) in TME is characterised as the cause of initiation and progression of tumourigenesis.
The purpose of this study is to develop an understanding of physical and mechanical forces that contribute to the remodelling of extracellular matrix in a cancerous environment to promote cancer development using a 3D cell culture model with collagen to mimic an in-vivo microenvironment.
Type I collagen was used to create a 3D model to investigate the mechanical properties under various conditions, such as changes in concentration, polymerisation pH and temperature, and presence of colorectal cancer cell lines, SW948 and SW1116, were used that exhibit differential metabolic phenotypes. Co-culture with fibroblast CCD-18Co was evaluated to recapitulate the stromal environment that the cells encounter in vivo to elucidate the changes ECM go through during tumour progression.
A microfluidic cell culture system was used to apply fluid flow and pressure gradient to a 3D collagen scaffold to understand the role of interstitial flow in matrix organisation, cancer growth and migration during cancer progression. They used their TA.XTplus Texture Analyser to perform mechanical testing on collagen samples. The study concluded that it is important to consider both tumour microenvironment and phenotype of cancer cells when considering the regulation of extracellular matrix. Read more
Gene Therapy
Gene therapy holds the potential to rapidly advance the treatment of cancer. Gene delivery is a necessary step in gene therapy for the introduction or silencing of a gene to promote a therapeutic outcome in patients. There are many different methods of gene delivery for various types of cells and tissues. Gene therapy efficacy can be improved by prolonging the release of nucleic acid drug payload for sustained, long-term treatment.
Scientists from Queen’s University Belfast have been investigating the influence of alginate backbone on efficacy of thermo-responsive alginate-g-P(NIPAAm) hydrogel as a vehicle for sustained and controlled gene delivery.
This study was designed to produce the optimal Alg-g-P(NIPAAm) hydrogel with respect to localised delivery of DNA nanoparticles as a potential medical device for those with castrate resistant prostate cancer (CRPC). Given that CRPC typically disseminates to bone causing pain, morbidity and a plethora of skeletal related events, a copolymer based hydrogel was designed to for long term release of therapeutic DNA nanoparticles.
Alginate grafted poly(N-isopropylacrylamide) hydrogels (Alg-g-P(NIPAAm)) form three-dimensional networks in mild conditions, making them suitable for incorporation of labile macromolecules, such as DNA. The impact of P(NIPAAm) on copolymer characteristics has been well studied, however the impact of alginate backbone characteristics on copolymer properties has to date not been investigated.
Six different Alg-g-P(NIPAAm) hydrogels were synthesised with 10% alginate, which varied in terms of molecular weight and monomer ratio, and with 90% NIPAAm to develop an injectable and thermo-responsive hydrogel formulation for localised gene delivery. They used their TA.XTplus to measure the injection force of samples. Hydrogel stiffness was found to be directly proportional to molecular weight and monomer ratio of the alginate backbone. Read more
Symptom Management and Palliative Care
In addition to these applications focussed on efficient and effective drug delivery and the specifics of tumour structure and properties, Texture Analysis has a large part to play in developing ways of keeping patients more comfortable, particularly when it comes to end of life or prolonged hospital care. These applications are also relevant to many other illnesses.
Dysphagia (difficulty swallowing) is a common symptom of cancers, either caused as a side effect of treatment, or because a tumour disrupts swallowing and the passage of food. This can cause problems with discomfort, weight loss and dehydration in cancer patients. Food and liquid texture play very important roles in the care of people with dysphagia, and so there have been countless publications characterising readily-available foods as acceptable to dysphagia sufferers.
There have also been many Texture Analysis investigations into thickeners and gelling agents as additives to liquids to promote a controlled swallowing process and add to the patient’s comfort.
Pressure sores are caused by pressure applied to the same area of skin for a long time period, and are consequently common during end of life care. When the patient cannot be moved due to aggravation of other symptoms, barrier creams and films are invaluable in alleviating discomfort. Physical properties of these products, such as cream spreadability or film strength, are measured using imitative or fundamental methods using a Texture Analyser.
A large number of drugs are still administered via hypodermic needle despite the progression of research into other drug delivery routes. The properties of the syringe and needle system can be investigated using a Texture Analyser, including the puncture force of the syringe tip, and the injection force of each combination of syringe and contents. The tailoring of all of these components can help create a more comfortable experience for the patient.
Chemotherapy and end of life dehydration can both cause a dry mouth. This can be uncomfortable, but there are products that can help alleviate this symptom such as artificial saliva in spray, gel, lozenge or pastille form. Texture Analysis is a key stage in the development of these products to ensure they are the correct consistency for provision of comfort, but also last a long time in the mouth to reduce the need for reapplication.
To find out more about Texture Analysis of pharmaceutical products, contact Stable Micro Systems today.
For more information on how to measure texture, please visit the Texture Analysis Properties section on our website.
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