# The Cell Membrane of _Sulfolobus_ spp.--Homeoviscous Adaption and Biotechnological Applications
## 5 Applications  
The monolayer architecture of archaeal membranes provides high mechanical strength and the lipid structure characterized by ether bonds, cyclopentane rings and saturation results in high enzymatic, chemical [116] and physical [117] stability. Generally, these characteristics of ether lipids, like stability towards high temperature and acidic pH, make them potentially interesting for biotechnological applications. The use as vehicles for gene or drug delivery, as so called archaeosomes, has received increasing attention [118]. For this application, their temperature stability is a crucial advantage over conventional liposomes made from ester lipids, during processing and storage, whereas the stability towards low pH predestines archaeosomal formulations for the use in oral drug delivery, since they protect their cargo from degradation in the stomach. In 1990, [PERSON] and [PERSON] verified that polar lipid extracts of _S. acidocaldarius_, grown at ~65 \({}^{\circ}\)C, could be used for the generation of archaeosomes [119]. Those formed archaeosomes exhibit the low permeability of the encapsulated fluorescein, due to the tight and rigid packing [120]. The use of archaeal membrane lipids for the generation of archaeosomes and their applicability have already been reviewed in several articles [69; 118; 121; 122]. Therefore, this chapter focuses on the latest findings regarding archaeosomes generated by lipids extracted from the _Sulfolobus_ genus. Generally, the most recent studies with archaeosomes are dominated by oral applications and are characterized by the fact that the investigated archaeosomes are constituted of a mixture between conventional lipids and TELs, e.g., the polar lipid extract of _Sulfolobus_ was used to enhance the properties of conventional liposomes. Archaeosomes composed of phospholipids, cholesterol and archaeal lipids derived from _S. islandicus_ showed that the vesicles could withstand in vitro exposure of bile salt measured by the loss of the entrapped marker. In contrast to the liposomes containing archaeal lipids, the conventional liposomes, composed of phosphatidylcholine, released almost the entire marker when incubated with bile salt. This serves as proof-of-concept for the possible usage of archaeosomes as an oral drug delivery system [123]. Archaeosomes were also used as carriers for insulin. They demonstrated higher stability in the gastrointestinal environment, in addition to overall lower levels of blood glucose indicated by an in vivo study, when compared to conventional liposomes [124]. Additionally, a number of in vivo studies have been carried out with archaeosomes to insulin, including applications for antibiotics, cancer, hepatitis B and D, as well as osteoporosis treatment [125; 126; 127; 128; 129]. A summary of the properties of archaeosomes in respect to the currently prevalent application of oral drug delivery in comparison with conventional liposomes is given in Figure 4.  
Apart from the oral delivery of drugs, archaeosomes of _S. acidocaldarius_ packed with methylene blue indicated a potential use in skin permeation treatment, as observed on rat skins. Albeit, the addition of cholesterol enhanced encapsulation, and thus, the release of the marker through the skin [130]. TELs extracted from _S. acidocaldarius_ in combination with phosphocholine were used to generate a liposome for the encapsulation of a drug called Ce6 used in the photodynamic therapy for cancer treatment. Due to the TELs in the liposomes, a slower release of the drug to the cancer cell could be achieved [131]. In another study, mixing cholesterol and TEL extracted from _S. acidocaldarius_ resulted in a stable vector for gene delivery used for the transfection of mammalian cells [132]. These applications, including the oral delivery of drugs, are summarized in Table 3.  
In summary, archaeosomes, specifically made with lipid extracts of _Sulfolobus_ genus, were found to be used for oral and intravenous drug delivery, gene delivery or as a skin permeation system.