**4. Challenges and Limitations**

The rapid adoption of the use of biopolymers is still hindered by several factors. First, research thus far has been conducted primarily in vitro; therefore, more in vivo and clinical trials are needed to demonstrate the health benefits of biopolymers and the biocompatibility in various biomedical applications, in particular when used as encapsulation materials for drug delivery. When used for the treatment of various diseases, more studies are needed to assess the appropriate compound: either alone or in combination to achieve the desired payload in a highly regulated and site-specific manner at therapeutically relevant concentrations [227].

A second challenge is to obtain materials with properties similar or better to synthetic products by improving end-use mechanical properties, kinetics and release, thermal resistance, and barrier properties. For example, some products exhibit low mechanical properties, rapid degradation, and high hydrophilic capacity especially in humid or adverse environments, rendering their application unviable.

Although numerous studies have examined the use of encapsulated probiotics, there is a need for in depth interdisciplinary research that includes microbiologists, medical doctors, and biomaterial, food, agro and chemical engineers. This will lead to better and more efficient prototypes of probiotic encapsulating formulations, to the identification of the most specific/effective probiotic strains, and to the most suitable polymeric carriers applied for product manufacturing. In addition, this will lead to the optimization of the entire process based on the natural characteristics and sensitivity of the selected strain, and will identify ways on how to develop the best formula based on in vitro, in vivo, and pre-clinical techniques considering the release, manufacturing, packaging, transportation, and storage of capsules. Third, the challenges related to costs, economic aspects, and the gap between policy and implementation of the new technologies on a global level need to be addressed in this rapidly emerging field.
