Showcasing research from Professor Mina Hoorfar’s laboratory, School of Engineering, University of British As featured in: Columbia, Kelowna, Canada. Nanomaterial-based encapsulation for controlled gastrointestinal delivery of viable probiotic bacteria Probiotics lose their viability during intestinal passage resulting in poor gastrointestinal delivery. Microencapsulation technology has been proposed as a successful strategy to address this problem by maintaining the viability of probiotics, thereby improving their effi cacy following oral administration. Nanomaterials have demonstrated a signifi cant promise as encapsulation materials to improve probiotics encapsulation. The integration of nanotechnology with microencapsulation See Mina Hoorfar et al., techniques can improve the controlled delivery of viable Nanoscale Adv., 2021, 3, 2699. probiotic bacteria to the gut. rsc.li/nanoscale-advances Registered charity number: 207890 Nanoscale Advances View Article Online REVIEW View Journal | View Issue Nanomaterial-based encapsulation for controlled gastrointestinal delivery of viable probiotic bacteria Cite this: Nanoscale Adv.,2021,3, 2699 Seyedehhamideh Razavi,†a Sajjad Janfaza,†a Nishat Tasnim, a Deanna L. Gibsonbc and Mina Hoorfar *a Probiotics are microorganisms that have beneficial health effects when administered in adequate dosages. The oral administration of probiotic bacteria is widely considered beneficial for both intestinal as well as systemic health but its clinical efficacy is conflicted in the literature. This may at least in part be due to the loss of viability during gastrointestinal passage resulting in poor intestinal delivery. Microencapsulation technology has been proposed as a successful strategy to address this problem by maintaining the viability of probiotics, thereby improving their efficacy following oral administration. More recently, nanomaterials have demonstrated significant promise as encapsulation materials to Received 13th November 2020 improve probiotic encapsulation. The integration of nanotechnology with microencapsulation Accepted 25th March 2021 techniques can improve the controlled delivery of viable probiotic bacteria to the gut. The current review Creative Commons Attribution-NonCommercial 3.0 Unported Licence. DOI: 10.1039/d0na00952k aims at summarizing the types of nanomaterials used for the microencapsulation of probiotics and rsc.li/nanoscale-advances showing how they can achieve the delivery and controlled release of probiotics at the site of action. 1. Introduction results for many diseases.15,16 This is in part due to the lack of viability of probiotics using traditional manufacturing and The World Health Organization denes probiotics as live packaging methods.17 Several factors (such as pH, oxygen, and microorganisms that confer various health benets to the host temperature) can signicantly affect the viability and survival when administered in adequate amounts at the desired target rate of probiotics during processing, storage, and passage This article is licensed under a site in the digestive tract.1 Probiotics have been reported to offer through the gastrointestinal tract.18 Thus, probiotics must be protection from enteric infectious disease,2 enhance metabo- able to survive the harsh gastric environment, remain meta- lism (including lactose intolerance,3 absorption of calcium,4 bolically active, and be released (in a controlled manner) in Open Access Article. Published on 30 March 2021. Downloaded 9/26/2021 11:27:17 AM. synthesis of vitamins and pre-digestion of proteins5), have anti- large enough quantities at the site of action in the lower carcinogenic and anti-mutagenic activities,6 and reduce symp- gastrointestinal (GI) tract to confer benecial health effects.19,20 toms associated with anxiety and depression.7,8 Probiotic Microencapsulation of probiotics has been proposed as an bacteria provide positive health responses based on three effective solution to improve the survival, resistance, and tar- mechanisms: production of nutrients and cofactors, competi- geted release of sensitive microorganisms in the GI tract.21 It is tion with pathogens for nutrients or adhesion sites, and stim- a technology for entrapping small quantities of bioactive ulation of the host immune response.9 Given their compounds and/or microorganisms in small polymer capsules. immunomodulatory potential, probiotics have potential in the In essence, the goal of microencapsulation is to create treatment of diseases such as inammatory bowel disease (IBD) a microenvironment that protects bacteria from exposure to and cancer,10–12 and have been proposed to treat a multitude of exterior factors (such as low gastric pH) during digestion, and immune and metabolic-driven diseases.13,14 subsequently to reduce cell injury or cell death before their While the potential of the use of probiotics in the treatment release at the target site.22 There are many reports on micro- or even prevention of gastrointestinal diseases is high, their encapsulation of probiotic bacteria resulting in highly clinical efficacy remains low due to conicting clinical trial enhanced viability of probiotics during storage and adminis- tration.23 The majority of these reports are based on the immobilization of probiotics into a polymer matrix, which aSchool of Engineering, University of British Columbia, Kelowna, BC, Canada. E-mail: retains its structure in the acidic environment of the stomach [email protected] bDepartment of Biology, Faculty of Science, University of British Columbia, Kelowna, before swelling or dissolving in the intestine as a result of the 24 Canada pH change. With the advent of nanotechnology, innovative cDepartment of Medicine, Faculty of Medicine, University of British Columbia, encapsulating materials (EMs) have recently been developed Vancouver, Canada based on nanostructured compounds. These nanomaterials † These authors contributed equally to this work and should be considered have shown improved properties for the encapsulation of co-rst authors. © 2021 The Author(s). Published by the Royal Society of Chemistry Nanoscale Adv.,2021,3, 2699–2709 | 2699 View Article Online Nanoscale Advances Review probiotics. Due to their unique physical and chemical proper- factors such as oxygen, temperature, and light during handling ties, nanostructured EMs demonstrate great promise for and storage is another challenge to be addressed. In this regard, protection of microorganisms from the acidic conditions of the microencapsulation has shown great potential in increasing the stomach and hence allow for the successful release of entrapped stability of probiotics.29,30 probiotic cells in the intestinal lumen with natural pH. Despite the remarkable improvement in viability and In this paper, we provide a critical review of nanomaterials in delivery of probiotic cells by encapsulation using traditional light of their suitability for probiotic microencapsulation. We materials and methods, there is still a need to develop new and provide an overview of nanostructured capsules used to protect innovative microcapsules for better protection of probiotics and probiotics from environmental and physiological factors (e.g., improved function. Using nanostructures as EMs has been pH, oxygen, and temperature) and their advantages and proposed as a promising approach to design an improved pro- limitations. biotic delivery system. 2. Microencapsulation of probiotics 3. Nanostructured encapsulating Microencapsulation of probiotics has been widely utilized in materials the food and pharmaceutical industries. Microencapsulation Nanostructured materials for the encapsulation of probiotics results in the protection of probiotics by encapsulating them in can be selected from a wide variety of natural polymers (e.g. small capsules. By building a functional barrier between the carbohydrates, gums, and proteins) and synthetic materials. cells and environment, the capsule prevents probiotic bacteria The composition of the EM affects the functional properties from damage, leading to improved viability of probiotics. of the microcapsule,31 and each group of encapsulating mate- Encapsulated cells can reach the site of action without being rials has its pros and cons in terms of mechanical, chemical, adversely affected by environmental factors such as oxygen and physical, and biological properties. Creative Commons Attribution-NonCommercial 3.0 Unported Licence. pH. Recently, many nanomaterials with different sizes, shapes, Exposure to a high oxygen environment is harmful to textures, and compositions have been investigated for the microaerophilic and anaerobic probiotics such as L. acidophilus microencapsulation of probiotics. Because of their unique (microaerophilic) and bidobacteria (obligate anaerobic). It can physical and chemical properties, nanostructured microcap- result in cell lysis due to the formation of reactive oxygen sules have shown promising improvement in protecting pro- species such as superoxides that can cause oxidative DNA biotics from harsh environments. The employed nanomaterials damage to bacterial cells. It has been shown that the viability of (e.g., nanocellulose) are nontoxic and compatible with both free anaerobic probiotic cells (e.g., Bidobacterium) upon expo- probiotics and the body while providing maximum protection sure to oxygen decreases,25 while encapsulated cells survive for to probiotic bacteria. Some of them are capable of releasing This article is licensed under a longer.26 loaded probiotics under certain conditions (e.g.