Advances in β-Galactosidase Research: A Systematic Review from Molecular Mechanisms to Enzyme Delivery Systems

Background/Objectives: β-galactosidase (lactase) is a transformative enzyme used in many different fields. Its significance spans from biotechnology to food and pharmaceutical industries. β-galactosidase catalyzes the hydrolysis of lactose into glucose and galactose. In medicine, β-galactosidase has gained attention and has many applications, mainly in enzyme replacement therapy. β-galactosidase is the main active ingredient of medications for lactose intolerance. Industrially β-galactosidase is typically produced by the Aspergillus oryzae filamentous fungus. Therapeutic interventions involving β-galactosidase aim to mitigate symptoms and improve the patients' quality of life. In the food industry, it plays a crucial role in the production of lactose-free products, improving accessibility to dairy products. However, despite its versatility and wide use, challenges connected to β-galactosidase still exist, such as the need for cost-effective and more efficient methods for administering the enzyme. Additionally, there are several ongoing studies that seek to enhance stability and optimize the performance of β-galactosidase in various applications. The aim of this manuscript is to summarize current knowledge about β-galactosidase as an active ingredient and to present some preparations that are commercially available or mentioned in the literature. Methods: A systematic search was conducted in PubMed, Scopus, Embase and Web of Science to identify relevant articles on formulations related to β-galactosidase, focusing on original research articles published between 1895 and 2025 that exclusively examine the use of oral drug delivery. Results: After a rigorous search across multiple databases, 45 relevant studies out of 1633 initial results were selected for analysis. Conclusions: β-galactosidase remains a highly versatile enzyme with broad industrial and medical relevance. While current formulations offer significant benefits, further innovation is needed to improve delivery efficiency, stability, and cost-effectiveness. The findings of this review contribute to a deeper understanding of β-galactosidase as an active ingredient and outline opportunities for advancing its application in oral drug delivery systems.