Review article Liposome-polymer complex for drug delivery system and vaccine stabilization Sriwidodo a, * , Abd. Kakhar Umar a, c , Nasrul Wathoni a , James H. Zothantluanga b , Sanjoy Das b , Jittima Amie Luckanagul d a Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Jatinangor 45363, Indonesia b Department of Pharmaceutical Sciences, Faculty of Science and Engineering, Dibrugarh University, Dibrugarh 786004, Assam, India c Department of Pharmaceutical Sciences and Technology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand d Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok 10330, Thailand ARTICLE INFO Keywords: Liposome-polymer complexation Liposome complex Targeted delivery Controlled release ABSTRACT Liposomes have been used extensively as micro- and nanocarriers for hydrophobic or hydrophilic molecules. However, conventional liposomes are biodegradable and quickly eliminated, making it difficult to be used for delivery in specific routes, such as the oral and systemic routes. One way to overcome this problem is through complexation with polymers, which is referred to as a liposome complex. The use of polymers can increase the stability of liposome with regard to pH, chemicals, enzymes, and the immune system. In some cases, specific polymers can condition the properties of liposomes to be explicitly used in drug delivery, such as targeted delivery and controlled release. These properties are influenced by the type of polymer, crosslinker, interaction, and bond in the complexation process. Therefore, it is crucial to study and review these parameters for the development of more optimal forms and properties of the liposome complex. This article discusses the use of natural and synthetic polymers, ways of interaction between polymers and liposomes (on the surface, incorporation in lamellar chains, and within liposomes), types of bonds, evaluation standards, and their effects on the stability and pharmacoki- netic profile of the liposome complex, drugs, and vaccines. This article concludes that both natural and synthetic polymers can be used in modifying the structure and physicochemical properties of liposomes to specify their use in targeted delivery, controlled release, and stabilizing drugs and vaccines. 1. Introduction A liposome is a drug delivery system composed of phospholipids and forms a bilayer membrane in an aqueous system. Liposomes have been used extensively as a drug delivery system to increase the solubility and permeability of hydrophilic or hydrophobic drugs. However, conven- tional liposomes are easily degraded by pH, enzymes, and the immune system in a biological environment. Therefore, its application in the provision of certain pathways will release the drug immediately, being unable to maintain the stability of the active substance. The conventional liposome quickly decomposes at acidic pH, so the delayed-release profile in the intestine cannot be obtained. The liposome can also be degraded by lipase in the digestive system [1, 2]. In systemic delivery, liposome can be recognized by the reticuloendothelial system (RES). This can decrease its bioavailability in systemic circulation [3, 4]. One solution to overcome this problem is through modification of the structure of the liposome by using a polymer. The complexation of the liposome-polymer is called a liposome complex. It is known that com- plexing liposomes using polymers can improve the physicochemical properties of liposome, so they can be explicitly used for targeted de- livery and controlled release of drugs. The liposome complex system becomes more stable and sturdy because it is better at protecting active substances from chemicals, enzymes, the immune system, and even photolysis reactions [1, 5, 6, 7, 8, 9, 10]. Surface modification of lipo- somes can be used to avoid bonding or adsorption of liposomes on some proteins during circulation. Besides, surface modification is intended for targeted drug delivery using ligands, receptors, or polymers that can stimulate the destruction of liposomes through pH, enzymes, or specific bonds on the cell matrix to initiate endocytosis and drug release [11]. Likewise, the incorporation of polymers in the bilayer chain or inside the This article is a part of the Lipid-Based Nanoparticles Special issue. * Corresponding author. E-mail address: sriwidodo@unpad.ac.id (Sriwidodo). Contents lists available at ScienceDirect Heliyon journal homepage: www.cell.com/heliyon https://doi.org/10.1016/j.heliyon.2022.e08934 Received 17 October 2021; Received in revised form 25 January 2022; Accepted 8 February 2022 2405-8440/© 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/). Heliyon 8 (2022) e08934