Liposomes as a drug delivery system

TIPS -February /981 tion causes a loss of anticonvulsant effect, or leads to anticonvulsant toxicity. The ability to monitor plasma anticon­vulsant levels as a routine has made avail­able a most valuable tool for the better use of these drugs. However it would only be fair to point out that the tool has been placed in the hands of a profession that has generally lacked the intellectual prepared­ness to use it optimally. This has sometimes led to therapeutic misadventure. The final aim of anticonvulsant therapy, the com­plete suppression of epileptic activity, has sometimes been lost sight of in a preoccu­pation with achieving therapeutic range plasma drug levels. Nonetheless, these shortcomings in contemporary practice do not deny the enormous benefits which may accrue from optimal use of plasma anticon­vulsant level monitoring. At the present time it would appear that the optimal use of currently available know­ledge and drugs can lead to the complete suppression and often to cure of a con­siderable majority of cases epilepsy when the disorder is not due to progressive brain disease and is treated early enough in its course. Prospects for anticonvulsant therapy If one puts aside the possibility of a spec­tacular leap in knowledge, conceivably in a quite unexpected direction, sober assess­ment suggests several areas in which research is likely to lead better treatment of epilepsy in the future. Firstly, there is the question of preven­tion. The two most frequent aetiological factors in epilepsy are birth injury to the brain, mechanical or hypoxic, and genetic predisposition. Better obstetrics may reduce the former, and indeed may have already done so, though the trend may not yet have had time to emerge because of the time lag between birth and the appearance of seizures. If the molecular basis common genetic type of generalized epilepsy could be determined, this type of epilepsy might also prove preventable. Probably, new anticonvulsants drugs will be introduced. However, until we know more of the electrical and biochemical mechanisms of epileptogenesis, no funda­mental basis exists for developing new anticonvulsant drugs. Without such a basis, any discovery of new types anticonvul­sant drugs is likely to be fortuitous. Know­ledge of the relevant mode or modes action of the currently-available anticon­vulsants could also help in finding new drugs. Here the problem is that too many biochemical and electrical effects of the anticonvulsants have already been detected, without their essential antiepilep­tic mechanisms of action being recognised among these various effects. Other useful but relatively pedestrian avenues for research would be the filling in the numerous small gaps in our know­ledge of anticonvulsant pharmacokinetics, elucidation of mechanism interaction between anticonvulsants, and the search for as yet undetected metabolites that several anticonvulsants must have, followed by the determination whether these metabolites are phar­macologically active. Further documenta­tion of the specificities various anticonvulsants is desirable. This should be done by, or in collaboration with, clinicians who have accurately diagnosed the type epilepsy and followed patients carefully over prolonged periods to ensure that epilepsy really is fully controlled. Also, in collaboration with these same clinicians, the existing therapeutic ranges of plasma anticonvulsant levels should be refined. The ranges may well differ a given drug in different types of epilepsy, and may also differ with activity of the epileptic process. If a sufficient body of data can be assem­bled and analysed it may be possible to replace therapeutic ranges with something approaching actuarial probabilities of con­trolling epilepsies of different types a variety of commonly encountered circum­stances. Biochemical mechanisms of vari­ous types of idiosyncratic toxicity anti­convulsant drugs might also be studied, in hope that this knowledge can reduce 39 the risk or severity of such unwanted reactions. If one looks into the foreseeable future, and allows that the researches suggested above can be brought to successful conclu­sions, one still suspect that the major problem in relation to anticonvulsant therapy will remain unresolved. This prob­lem already exists as rna jor limitation to optimal contemporary anticonvulsant therapy: the failure of patients to take their drugs in the prescribed dosages over the long periods during which the drugs must be used. In a society which continues to hold contemporary philosophical values, the best answer to this problem seems lie education of patients. Whether such education can be achieved is another matter. Reading list 1 Eadie, M. J. and Tyrer, H. (1980)Anticonvulsant therapy. Pharmacological basis and practice 2nd edn. Churchill-Livingstone, Edinburgh 2 Guelen P. J. M. and van der Kleijn, E. (1978) Rational anti-epileptic drug therapy Elsevier, Ams­terdam 3 Richens, A. (1976) Drug treatment of epilepsy Kimpton, London 4 Schneider. H., Janz, D., Gardner-Thorpe, C., Meinardi, H. and Sherwin, A. L. (1975) Clinical Pharmacology of antiepileplic drugs. Springer, Berlin Woodbury, D. M., Penry, J. K. and Schmidt, R. P. (1972)Anli-epileplic drugs Raven Press, New York Mervyn J. EadU! is Neurologist to the Royal Brisbane Hospilal, Brisbane, Australia and ProfossorofCiinical Neurology and Neuropharmacol'>gy at the University Queensland. Liposomes as a drug delivery system Rudolph L. Juliano Department Pharmacology, University Texas Medical School, Houston, Texas, U.S.A. The concept of controlled drug delivery is not new to pharmacology. A considerable amount of ingenuity has been expended in attempts to alter pharmacodynamic characteristics drugs, including their clearance rates, tissue penetration, metabolism and excretion, through chemi­cal modification drug structure. More recently there has been a good deal of interest in possibility of coupling a drug to a carrier or delivery system which could then modulate the pharmacodynamic behavior of the drug in a beneficial way. The carrier systems which have been explored range from simple sus-tained release devices to highly selective conjugates of drugs with cell-type specific antibodies. Perhaps the most excitement, however, has been engendered by the approach of using liposomes as a drug carrier'. Liposomes, that is phospholipid vesicles, have long been a valuable tool for biochem­ists and cell biologists involved in the study of membrane phenomena. About eight years ago a number of investigators real­ized that the liposome was an attractive candidate drug delivery system. Encapsulation or packaging of a drug within liposomes would, no doubt, produce ©Elsevier/North-Holland Biomedical Press 1981