Liposomes as Tools to Improve Therapeutic Enzyme Performance

Abstract

The drugs concept has changed during the last few decades, meaning the acceptance of not only low molecular weight entities but also macromolecules as bioagent constituents of pharmaceutics. This has opened a new era for a different class of molecules, namely proteins in general and enzymes in particular. The use of enzymes as therapeutics has posed new challenges in terms of delivery and the need for appropriate carrier systems. In this review, we will focus on enzymes with therapeutic properties and their applications, listing some that reached the pharmaceutical market. Problems associated with their clinical use and nanotechnological strategies to solve some of their drawbacks (i.e., immunogenic reactions and low circulation time) will be addressed. Drug delivery systems will be discussed, with special attention being paid to liposomes, the most well-studied and suitable nanosystem for enzyme delivery in vivo. Examples of liposomal enzymatic formulations under development will be described and successful pre-clinical results of two enzymes, L-Asparaginase and Superoxide dismutase, following their association with liposomes will be extensively discussed.

Liposomal Delivery of Newly Identified Prophage Lysins in a Pseudomonas aeruginosa Model

“…Another alternative consists in the incorporation of lysins in lipid-based systems, such as liposomes, aiming to deliver the loaded lysin to the peptidoglycan layer. Liposomes are spherical structures constituted by one or more phospholipid bilayers, separated by aqueous compartments, which allows them to incorporate hydrophilic or hydrophobic compounds [ 19 , 20 ]. This strategy has demonstrated an improvement to the pharmacokinetic profiles of loaded compounds and, consequently, their therapeutic activity both in vitro and in vivo [ 20 , 21 , 22 , 23 ].…”

Nanotechnology as a Promising Method in the Treatment of Skin Cancer

“…It is important to note that one of the most commonly used methods today is to coat the surface of the liposome with polyethylene glycol (PEG), creating what is known as long-circulating liposomes or 'stealth liposomes'. Obviously, it is possible to further modify the surface of the liposomes by incorporating various ligands onto the surface of the liposome, such as glycoproteins, immunoglobulins, peptides, transferrin, etc., in order to preferentially target them to overexpressed receptors in tumor cells [84].…”

“…Encapsulation of doxorubicin, paclitaxel, or 5-fluorouracil improves their pharmacokinetics, thus increasing their half-life in cancer cells [84][85][86]. Sing et al [86] showed that the encapsulation of DOX and celecoxib (CEL), a non-steroidal anti-inflammatory drug, in liposomes significantly increased the biological activity of chemotherapeutic agents in human skin carcinoma A431 cell culture.…”

Fluorinated dendritic amphiphiles, their stomatosome aggregates and application in enzyme encapsulation

“…7 Alternatively, amphiphiles can be used to form vesicles: polymersomes in the case of amphiphilic polymers or liposomes for lipids. 8,9 Using encapsulation, only little enzyme is denatured as it does not interact with the carrier. The effective increase in size and subsequent change in physical properties after encapsulation means the enzymes can be separated by either centrifugation or filtration.…”