Liposomes clinical applications

External stimuli have also been used to further target liposomes. In one such study magnetite particles were incorporated in radiolabeled liposomes and a magnet positioned over the right kidney of a test animal. The liposomes were selectively targeted to that kidney in concentrations that were viewed as significantly high for relevant clinical applications [66],... 

Several liposome-based drugs have been approved for clinical application [64]. One of the clinically approved liposomes is Doxil, a PEGylated liposome containing doxorubicin (DOX), which is used for the treatment of a number of diseases [65]. As shown in this case, in the field of liposome drug development, PEG is widely used to protect the liposome from recognition by opsonins, thereby reducing liposome clearance. 

Gabizon A, Goren D, Cohen R, Barenholz Y (1998) Development of liposomal anthracyclines from basics to clinical applications. Journal of Controlled Release 53 275-279. 

Progress in the field of drug targeting has been slow till thirty years ago. With the advent of the monoclonal antibody technology in the mid seventies of the last century as well as the development of liposomal devices as carriers did the drug targeting field expand and did the clinical application become a feasible aim. 

What has been achieved until now In the year 2001, several liposome and antibody based strategies have been or will soon be approved for clinical application, some for the treatment of cancer, some for the treatment of bacterial infections, some for chronic inflammatory diseases. Furthermore many monoclonal antibodies without a drug or pharmacologically active molecule attached are in the clinic. Their intrinsic targeting and effector function is obviously sufficient for the pharmacological effect. 

Immordino ML, Dosio F et al (2006) Stealth liposomes Review of the basic science, rationale, and clinical applications, existing and potential. Int J Nanomedicine 1(3) 297-315... 

In the last few decades, the discovery of SPs from natural sources with potent antiviral activities has increased significantly, but their clinical application against human viral infections is still far from being satisfactory. The therapeutic perspectives of SPs will probably improve with an adequate formulation in a clinically useful vehicle. The development of new drug delivery systems, such as encapsulation in liposomes or nanoparticles, is a strategy currently gaining attention to improve the in vivo effectiveness and reduce the adverse effects of polysulfates. The potential of these natural compounds to prevent a wide spectrum of severe viral diseases warrants further investigation to ameliorate their administration in systemic virus infections. 

Systemically administered liposome-encapsulated bisphosphonates (e.g., clodronate or alendronate) have been shown to be effective, in rat and rabbit models, in the prevention of restenosis. This complication frequently occurs following percutaneous coronary interventions. Thus, these compounds show considerable promise for clinical application in this area [31]. 

TABLE 4 Liposomal Drugs Approved for Clinical Application or Undergoing Clinical Evaluation... 

The clinical applications of liposomes are well known (Table 4). The initial success achieved with many liposome-based drugs has fueled further clinical investigations. One of the drawbacks of the use of liposomes is the fast elimination from the blood and capture of liposomal preparations by the cells of the reticuloendothelial system (RES), primarily in the liver. 

Nanoparticles were first developed in the mid-seventies by Birrenbach and Speiser. Later on, their application for the design of drug delivery systems was made available by the use of biodegradable polymers that were considered to be highly suitable for human applications. At that time, the research on colloidal carriers was mainly focusing on liposomes, but no one was able to produce stable lipid vesicles suitable for clinical applications. In some cases, nanoparticles have been shown to be more active than liposomes due to their better stability.This is the reason why in the last decades many drugs (e.g., antibiotics, antiviral and antiparasitic drugs, cytostatics, protein and peptides) were associated to nanoparticles. 

Among the several drug delivery systems, liposomes - phospholipid nanosized vesicles with a bilayered membrane structure - have drawn a lot of interest as advanced and versatile pharmaceutical carriers for both low and high molecular weight pharmaceuticals. At present, liposomal formulations span multiple areas, from clinical application of the liposomal drugs to the development of various multifunctional liposomal systems to be used in therapy and diagnostics. This chapter provides a brief overview of various liposomal products currently under development at experimental and preclinical level. 

Some liposomal drugs approved for clinical application or under clinical evaluation (in different countries, same drug could be approved for different indications)... 

The development of pharmaceutical liposomes is an ever growing research area with an increasing variety of potential applications, and encouraging results ftom early clinical applications and clinical trials of different liposomal drugs. 

Niven et al. [18] have demonstrated that small liposomes also have a slower release rate than do large multilamellar vesicles following nebulisation. It has also been suggested that liposomes of 50-200mn diameter are optimal for clinical applications, as they tend to avoid phagocytosis by macrophages and still trap useful drug loads [19]. 

With their ability to achieve delivery to the cytoplasm, fusogenic liposomes, possibly containing polyethylene glycol (16) offer the potential for clinical application for cellular delivery of enzymes and DNA into cells (12,17 19). 

Hillery, A.M. (1998a) Liposomal drug delivery. II. Clinical applications, Pharm. J., 261,712-715. 

Jori, G. (1992) Low-density lipoproteins-liposome delivery systems for tumor photosensitizers in vivo, in Henderson, B.W. and Dougherty, TJ. (Eds.), Photodynamic Therapy. Basic Principles and Clinical Applications, New York Marcel Dekker... 

Allen TM, Cullis PR. Liposomal drug delivery systems From concept to clinical applications. Arfvawcerf Drug Delivery Reviews. 2013 65(l) 36-48. 

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