Review Article Health and Primary Care Volume 4: 1-4 ISSN: 2515-107X Health Prim Car, 2020 doi: 10.15761/HPC.1000188 Ligand-targeted liposomes Ahmed Mustafa Khidir 1 and Ali Awadallah Saeed 2 * 1 Department of Pharmaceutical Science, Faculty of Graduate Studies, Omdurman Islamic University, Sudan 2 Department of pharmacology and therapeutics, Pharmacy program, Napta College- Khartoum, Sudan Abstract e field of ligand-targeted liposomes (LTLs) has expanded rapidly and many experiments have shed light on some of the factors involved in the successes and failures of ligand-targeted liposomes. Ligand-targeted liposomes have the potential to revolutionize the treatment of cancer. However, these highly engineered liposomes generate new problems, such as accelerated clearance from circulation, compromised targeting owing to non-specific serum protein binding, and hindered tumor penetration. *Correspondence to: Ali Awadallah Saeed, Department of pharmacology and therapeutics, Pharmacy program, Napta College- Khartoum, Sudan, Tel: 249912320825; E-mail: alimhsd@gmail.com Received: March 25, 2020; Accepted: April 14, 2020; Published: April 17, 2020 Ligand Mediated Targeting e search for the 'magic bullet in anti-cancer therapy, as proposed by Ehrlich in the early 1900's continues. is hypothetical agent has selective toxicity towards a target population of malignant cells, but not 'normal' cells. Unfortunately, there are a limited number of features that distinguish malignant from non-malignant cells and that can be exploited to increase the selectivity of chemotherapy. However, the differential over-expression of cell surface antigens and/or receptors opens up the possibility for antibody-directed therapy. Since the advent, by Kohler and Milstein, of methods to produce large-scale quantities of monoclonal antibodies (mAb's), there has been an increasing trend towards the use of antibodies to target therapeutic agents. Included in the growing list of agents that have been conjugated to mAb are toxins and liposomes. Antibodies were the first ligands that were coupled to liposomes and the resulting formulations were named immunoLiposornes. More recently, other ligands, such as peptides that can bind to tumor specific antigens have also been used. Collectively, liposomes that have had a ligand coupled to their surface are referred to as 'ligand targeted liposomes', or abbreviated to 'targeted-liposomes'. e development of these formulations has focused on the achievement of certain characteristics that constitute the 'ideal targeted-liposome'. e first requirement is a rapid and simple method to couple ligands to the liposome surface. In this regard, it is important to consider the labile nature of some ligands, particularly antibodies, and potentially some liposome components. is means that they will not endure lengthy, multi-step protocols. Secondly, the chosen coupling method needs to be efficient to minimize wastage of ligand and coupling lipid. In many cases the ligand is either expensive, or difficult to prepare (in the case of mAb), or both. In addition, because the coupling lipid introduces functional groups (vide infra) that may be reactive in vivo if leſt exposed (i.e. not conjugated to antibody); the minimum amount should be incorporated into the liposomes to avoid possible toxicities and potential for opsonization. ird, the antibody density should be optimized to achieve specific targeting and reasonable circulation times. In this regard, the pharmacokinetics of immunoliposomes have been well studied. Not surprisingly, the attachment of antibodies to liposomes accelerates the rate of liposome clearance from circulation. It is likely that the IgG acts as an opsonin, similar to its normal immunological function. Fortunately, the antibody density can be decreased to a level where reasonable circulation times and effective targeting cm be mutually achieved. For whole antibodies (MW=150 000 Da) the optimal density is generally between 30-60 µg/µmol liposome PL. However, the optimal ligand density will be affected by several ligand-dependent factors including its targeting effectiveness, and immunogenicity. Fourth, the ligand must retain the ability to bind to its target. An important consideration here is the preservation of the Ligand structure. AIso, the ligand must be accessible for target recognition. Fiſth, the coupling method and the attachment of the chosen ligand should not affect the drug loading and retention characteristics of the resulting liposomes in a negative way (Figure 1) [1]. Ligand-targeted Stealth liposomes e inherent target selectivity of Stealth liposomes, based on the preferential accumulation and leaking into the tumor vascular bed, can be dramatically enhanced by chemically coupling tumor- specific monoclonal antibodies or antibody fragments (stabilized immunoliposomes, SIL) or another targeting moiety (peptides, carbohydrates, glycopropteins, receptor ligands), i.e. essentially any molecule that selectively recognizes and binds to target antigens or receptors over-expressed or selectively expressed on cancer cells. e ability to selectively target liposomal anticancer drugs via specific ligands against antigens expressed on malignant cells could improve the antitumor activity of the liposomal formulations. Targeted liposomal delivery to cancer cells aims to increase the therapeutic efficacy at the target and to minimize nonspecific toxicities. In fact, the greater advantages of targeted liposomes encapsulating cytotoxic drugs over free drugs has been unquestionably demonstrated in a number of experimental models of malignancy, including neuroblastoma and melanoma [3].