Child Malnutrition

On 23 March 2021, Dr Sheng Qi, leader of the Global Research Translation Award (GRTA) Child Malnutrition sub-project, hosted an online conference for partner teams based in Brazil, Jordan, Malaysia and Thailand. 

The GRTA project is funded from the UK government’s Global Challenges Research Fund (GCRF) to fast-track promising research findings into real-world solutions. The Child Malnutrition sub-project is developing low-cost and child-friendly micronutrient supplements with regional partners in Brazil, Jordan, Malaysia and Thailand. 

From onsite to online

When the project started in October 2019, the partners intended to meet at UEA in 2021 to exchange impressions and experience as well as lessons learned from the project, to receive training and to observe research in Dr Sheng’s laboratory. However, the COVID-19 pandemic meant the team had to alter plans, and the conference was held on MS Teams instead. Due to the geographical spread of the partners, we struggled to find a time to suit everyone. We are grateful to the Brazil team for agreeing to join at 04:00, very early in the morning!

Sharing findings

Dr Sheng Qi opened the conference with an introduction to research happening in her lab at UEA, using 3D printing and electrospinning techniques to produce orodispersible films. These small thin films dissolve rapidly in the mouth, making them an ideal choice for micronutrient supplements designed for children, who would struggle to swallow pills or liquids. 

Following Sheng’s talk, Session One was dedicated to the four partners presenting findings from their research to date:

• Dr Chan Siok Yee, Universiti Sains Malaysia, described the development of a prototype supplement using locally and sustainably sourced red palm oil, which is a source of vitamin A. Vitamin A is traditionally administered in tablet or capsule form (e.g. cod liver oil), which is not suitable for children. The team have developed a formulation to effectively encapsulate the red palm oil into an emulsion, which can then be electrospun into nanofibers to create a thin oro-dispersible form. The team have added Vitamin D and Zinc to the formulation, as these nutrients are also deficient in the Malaysian population. The next step is to trial this prototype in indigenous communities with parent consent, pending ethical approval.
• Dr Pratchaya Tipduangta, Chiang Mai University, Thailand, outlined their work to produce a prototype gummy supplement, enriched with B vitamins, vitamin C, calcium and iodine. The team were able to visit schools in rural Chiang Mai before the pandemic to conduct taste tests of prototype flavours and undertake surveys of eating habits. The team have fine-tuned the formulation for the chewy gummy supplement in their laboratories and are now exploring options for locally sourced ingredients and packaging. They are also awaiting ethical approval to carry out further taste trials in children. 
• Dr Lorina Bisharat, University of Jordan, and Dr Alberto Bernardi, Applied Science Private University, are a married couple who met whilst doing their doctorates at UEA. Together they are developing a prototype supplement designed to counter vitamin D and iron deficiencies in Jordanian children. To begin with they explored options to make gummies and medicated fruit films, but there is not capacity currently in Jordan to mass produce these. Therefore, they have formed a partnership with a Jordanian industrial pharmaceutical company called Sana Pharma to develop a prototype chewable tablet in two flavours, tutti-frutti and chocolate. Alberto is carrying out research into whether children prefer less rapidly dissolving chewable tablets or more rapidly dissolving oro-dispersible tablets. The next steps for the Jordanian team are to carry out stability studies, scale up manufacturing and register the product.
• Prof Humberto Ferraz, Sao Paulo University, Brazil, has been developing oro-dispersible tablets in his Deinfar laboratory for communities in Brazil. He shared the tablet formulation development and stability study of the formulations. With an existing industrial partner, Humberto’s team have already brought pharmaceutical produce with similar technology to the Brazilian market, but the pandemic has severely hampered their access to the laboratory to develop this particular product. 

Different perspectives

In Session Two, three invited speakers presented their perspectives of child malnutrition:

• Dr Saipin Chotivichien is the Director of the Bureau of Nutrition, Ministry of Public Health, Thailand. She described the Thai government approach to translating Global Nutrition Targets like the Sustainable Development Goals into national policy. The current National Plans of Action for Nutrition (NPANs) seek to create regulation around nutrition and food labelling, at the same time as educating Thai people on healthy eating and monitoring important indicators. The Thai government have a policy called the ‘Miracle of the First 1000 Days of Life’ which provides pregnant women with iron, iodine and folic acid supplements, and universal schemes to provide children with iron supplements (syrup and tablets). 
• Dr Geeta Appannah, Universiti Putra Malaysia, talked about the global silent pandemic of child malnutrition. She explained that child malnutrition can take three forms: undernutrition (wasting/stunting/underweight), overnutrition (overweight/obesity) and micronutrient deficiencies. More than one in three developing countries are affected by undernutrition and obesity. In some countries, all three forms are present, and an individual can suffer from different forms of malnutrition throughout their life. 
• Dr Clare Campbell, Octopoda Innovations, UK, is advising the partners on the GRTA sub-project with respect to technical queries around developing supplements for the market. She explained the advantages and disadvantages of different formats of nutritional supplements for children, and most important aspects to consider when developing a product. 

Thinking ahead to maximise impact

In Session Three, the partners gathered with the impact team from the GRTA project, including Asher Minns (science communications), Jean McNeil (creative writer) and Christine Cornea and Alex Smith (filmmakers) to discuss plans around impact and engagement in 2021. Originally, Jean, Christine and Alex had planned to visit the partner countries to create written and visual outputs to use in engagement with target communities and policy makers. 

This travel cannot happen due to COVID-19 so the teams are adapting their methods to create outputs. By filming interviews using video conferencing platforms and the participants own mobile phones, and sub-contracting video work to filmmakers in each country, the teams will produce films collaboratively and remotely. The story will focus on the tenacity of the partners to continue their research through the constraints of a pandemic, and the value of international partnership working and Overseas Development Assistance (ODA) research funding to translate world-class science into real-world improvements. 

Chiang Mai University, Thailand, is a partner with the Global Research Translation Award’s Child Malnutrition sub-project. Led by Dr Pratchaya Tipduangta from the Faculty of Pharmacy, the Thai team is developing dietary supplements to deliver micronutrients which are deficient in Thai children’s diets. This innovative approach to tackling child malnutrition is being trialled in four countries through the GRTA project: Thailand, Brazil, Jordan and Malaysia.  

School children feedback on flavour 

The Thai team visited four schools in two provinces (Chiang Mai and Mae Hong Son) to conduct taste testing of their prototype supplement. The surveys showed that 62% of children preferred to take dietary supplements in a jelly gummy form as opposed to a tablet.  

240 children tucked into different flavours of gummy: strawberry, mulberry, passion-fruit and orange. Strawberry was the most popular flavour in all age categories (6-12 years old), with 58% of children deciding this was their favourite, compared to 19% mulberry, 14% passion-fruit and 10% orange. 

Taste testing at a school in Thailand and close up of different flavours of gummy supplements

Children’s eating habits surveyed 

Whilst the researchers visited the schools to carry out taste tests, they took the opportunity to find out more about the children’s eating habits. In collaboration with the Chiang Mai provincial public health office, the team designed a survey to find out what snacks the children eat and how often. 

The children expressed a preference for potato chips or baked snacks, closely followed by jelly-type snacks, then crackers. Children had a lower preference for local snacks like Thai Sweet Crispy Rice (Khao Tan).  

The surveys showed that 43% of children have a snack every day, usually in the afternoon, but fortunately for most children this doesn’t inhibit their appetite for their evening meal.  

The team also asked questions about the children’s oral care regimes. The results showed that most of these 240 children brush their teeth regularly, but 18 children (7.5%) said they never brush their teeth. 

Survey of school children's snack choices and close up of some typical commercially available Thai snacks

Prototype development 

Following feedback from surveys, the team have been working in the laboratory to develop a micronutrient supplement which has a strawberry flavour and a texture similar to popular jelly gummy sweets. In the lab, they have been testing their prototype in comparison to a commercial sweet for characteristics such as hardness, cohesiveness, springiness and chewiness. This analysis is done using a texture profile analyser and is yielding promising results.   

Preparing prototype gummy supplements in the laboratory and testing them with a texture analyser

Future work 

The next part of the project will be to add the vitamin supplements to the gummy prototype and evaluate the antioxidant properties. The team will then finalise the recipe for ethical approval by the ethical committee at Chiang Mai University and prepare data for product registration. A key component of this project which is seeking to address the Sustainable Development Goals is fostering collaborations with industries within the partner countries. The Thai team are investigating local sustainable suppliers for their product ingredients and contacting Thai companies who could produce the supplements at scale.  

Blog written by Hannah Gray, GRTA Project Officer at UEA and Dr Pratchaya Tipduangta, Lecturer in Pharmaceutical Sciences at Chiang Mai University on 1 October 2020.   

The Global Research Translation Award (GRTA) project is funded from the UK government’s Global Challenges Research Fund (GCRF) Innovation and Commercialisation Programme, developed to fast-track promising research findings into real-world solutions. UEA is leading a £1.36 million project to help tackle health, nutrition, education and environment issues in developing countries.  

One of the sub-projects is coordinated by Dr Sheng Qi at the School of Pharmacy, University of East Anglia (UEA), developing low-cost and child-friendly micronutrient supplements with regional partners in Brazil, Jordan, Malaysia and Thailand. In this blog, Research Associate Thomas McDonagh describes some of the innovative methods the team at UEA are using to create customized supplements which are easy for children to consume.   

Oral dispersible films (ODFs) 

The research team at UEA are developing novel fabrication methods for manufacturing oral dispersible films (ODFs) to combat child malnutrition in developing countries. ODFs are thin flexible films which can be administered orally, efficiently delivering desired nutrients to the recipient. The small, readily dissolvable films are ideal for small children that struggle to swallow pills and tablets. They are also effective for nutrient delivery because the active ingredient diffuses directly into the bloodstream in the mouth, bypassing the gastrointestinal tract. Crucially for this project, the vitamins and minerals in the ODF can be tailored to the specific dietary deficiencies of each country to combat child malnutrition effectively and efficiently.  

In this project we are particularly interested in electrospinning and 3D printing for creating the ODFs. These two fabrication methods give us a large degree of control over the inner geometry of the film, which enables disintegration times and drug release profiles to be fine-tuned. By characterising and controlling these parameters we hope to create a drug delivery platform that can be tailored to specific populations and applications. 

Electrospinning  

One of the methods we are exploring is a relatively recent electrospinning technique, called emulsion electrospinning, which creates very thin, highly porous ODFs with both an aqueous and lipid phase. Different types of micronutrients usually have good solubility in only one of the two phases which limits application. By including both phases in the same ODF, we can incorporate water soluble compounds such as iodine, and lipid soluble compounds such as vitamin D, thereby reducing the amount of supplements a child needs to take.  

Electrospun fibres (see picture below) are incredibly thin, up to 1000 times thinner than a strand of hair, giving them a huge surface area to volume ratio. This means the film will disintegrate rapidly in the mouth. 

3D printing  

Through a partnership with PCE automation, a regional engineering company, we have gained use of an exciting high-end 3D printer, called the Arburg FreeFormer. The Freeformer can print intricate structures with a high degree of accuracy and more importantly has the flexibility to allow us to print with our own custom materials. Before the Covid-19 lockdown, we experimented with the geometric capabilities of the machine using a standard 3D printing material. 

A few of the lattice structures printed during this experimentation are shown to the right. By controlling the surface area to volume ratio and pore geometry it is possible to alter the degradation and release profiles of the micronutrients, creating dosage forms that can release immediately or over a prolonged period of time. 

Future work 

Following on from the promising fabrication of electrospun and 3D printed ODFs we will perform micronutrient release studies and conduct taste testing trials to assess patient compliance. We hope to welcome our GRTA partners from Jordan, Thailand, Malaysia and Brazil to UEA to share knowledge. Each partner will adjust supplement composition and flavour based on profiles of local populations. The partners are working with industrial partners in their own countries to maximise local capabilities for the long-term and low-cost production of supplements to ensure sustainability. 

Blog written by Thomas McDonagh, Research Associate at the School of Pharmacy at UEA and Hannah Gray, GRTA Project Officer at UEA on 24 June 2020.  

Creative writer Jean McNeil visited the Brazilian partner of the GRTA Child Malnutrition sub-project in early March 2020. The Deinfar lab, in São Paulo, Brazil, is developing micro-nutrient supplements, which will be subsequently tested by children and parents. The sub-project aims to develop innovative low-cost supplements suitable for children, and scale-up production and commercialisation in four low- and middle-income countries. 

The GRTA Child Malnutrition project 

The Global Research Translation Award (GRTA) project is funded from the UK government’s Global Challenges Research Fund (GCRF) Innovation and Commercialisation Programme, developed to fast-track promising research findings into real-world solutions. UEA is leading a £1.36 million project to help tackle health, nutrition, education and environment issues in developing countries.  

One of these sub-projects is working with Dr Sheng Qi (School of Pharmacy, University of East Anglia) to develop low-cost and child-friendly micronutrient supplements with regional partners in Brazil, Jordan, Malaysia & Thailand. The project aims to build capacity for research and development within the four countries to enable future development of similar products independently. The project is using creative writing and film-making to effectively communicate with supplements users, the general public and local governments, highlighting the importance of a balanced nutritional diet for child growth and development.  

What is the role of Sheng’s lab? 

Dr Sheng Qi and her team are focused on developing innovative and accessible technologies to tackle unmet healthcare needs. By working with industrial partners as well as cross-discipline collaborators, Sheng’s group is aiming to contribute to the interdisciplinary research area of enhancing the therapeutic effects of supplements and drugs via tailoring the dosage forms and the physical chemistry of drug formulations. 

Watch a short video of Sheng’s work 

Taking the core technology platform developed by Sheng during her previously funded UEA QR GCRF project which ended in October 2019, the Global Research Translation Award enables Sheng to collaborate with leading academics in Official Development Assistance (ODA) countries to produce micronutrient supplements. Each partner will adjust micronutrient supplement composition based on deficiencies within local populations, and develop relationships with industrial partners in their own countries to maximise local capabilities for the long-term and low-cost production of supplements. 

The Deinfar laboratory in Brazil 

Jean McNeil, a creative writer at UEA, flew to the University of São Paulo (USP) to visit the Deinfar lab in the School of Pharmaceutical Sciences in March. The Deinfar lab was specially created to interact with the pharmaceutical industries interested in seeking innovation and knowledge generated within the University. Jean filmed an interview with the lab lead, Dr Gomes Ferraz, to gain background and insight into his collaboration with Sheng. Jean met with Dr Gomes Ferraz’s colleagues and students at the lab and filmed the production of the prototype supplement samples at the Deinfar lab.  

What happens next? 

Jean now has enough material to develop the content for information leaflets, which will be distributed to school children and parents for subsequent testing of the products in Brazil. The GRTA Partners in Jordan, Thailand and Malaysia are also working on the formulation development and consulting with pharmacists, paediatricians and supplement producers. Back at UEA, Sheng and Research Associate Thomas Mcdonagh are investigating some simple, cheap and novel approaches to produce fast disintegration oral films using biopolymers from food wastes that are abundant in the partner countries, to be able to share further learning with their partners.  

NB. The Covid-19 pandemic is likely to have an impact on the timely progress of the GRTA project, as some of the labs are in lockdown and international travel is disrupted. 

Jean McNeil is a Reader in Creative Writing in the School of Literature, Drama and Creative Writing at UEA. Sheng Qi is Reader in the School of Pharmacy at UEA. Blog written by Elettra Spadola, GRTA Project Administrator at UEA. Photos by Jean McNeil.