Drug delivery and drug targeting is a scientific article written by Robert Langer for the nature publishing group. Langer uses his previously written journal articles along with external sources to compose a detailed overview of current and future lipid and polymer based drug delivery systems. This article covers the progression of drug delivery systems in 1998 along with the challenges faced by scientists with regards to delivery systems and delivery routes. This article provides a good analysis of the drug delivery systems that were present or in development in 1998 using illustrations and an extensive source of literature. Langer had a significant involvement in many of the delivery systems and claims in the discussion section that in “10 to 20 years many of the systems discussed would be introduced and in place”1. This enables a comparative of the delivery systems in present day.
Langer begins his article by introducing the topic of drug delivery by stating the impact of new drug delivery systems on various branches of medicine at the time. This is followed by a short description of the advantages of improved drug delivery systems weighed against the concerns this provides a good overview of the position of drug delivery in 1998. Langer then moves into the topic of polymer based drug delivery systems he firstly explains the mechanisms by which polymers can deliver drugs. Langer explains these mechanisms in detail using an efficient illustration of four different polymer systems. The author then further describes polymer based drug delivery regarding the challenges faced with regards to controlled release of the drug inside the polymer. One of these challenges is bulk erosion of the polymer causing dose dumping of the drug. There are several systems outlined in the article to achieve controlled release of drugs in polymer based systems. Such synthesised polymers include hydrophobic polyanhydrides, biodegradable hydrogels and also drug-polymer conjugates that are involved in passive targeting. Langer then proceeds to describe issues and developments regarding liposome based delivery systems. Langer begins by providing concise description of what liposomes are before directly comparing liposomes to polymers stating that liposome systems have “the advantage of providing a higher drug carrying capacity”2 but had issues regarding shelf life, targeting specific tissues and negative immune responses. These issues were resolved by altering the liposome surface. Intelligent delivery systems are also described by Langer with the purported purpose of pulsatile delivery as some drugs will not be as efficacious with constant or decreasing drug delivery rates. Early approaches to pulsatile delivery using magnetic beads are described using an illustration. Ways of improving intelligent delivery designs are outlined in the article such methods include the use of ultrasound, electric current, hydrogels and antibodies are used. These methods can alter the drug release rates of drugs along with the cells at which the drug targets. Langer goes on to describe the delivery systems specific to different delivery routes. The first route described is pulmonary in which the author compares liquid form inhalers which only 10% of the drug is received by the lung to a more efficient powder form inhaler in which 20-50% can be received by the lung. Langer goes on to describe the challenges associated with oral and transdermal delivery routes along with new systems and new approaches to overcome the common issues arising with each route.
The author throughout the article talks about new drug delivery systems along with new approaches to improve drug delivery systems 1998. As Langer was involved in the development of many of the articles systems and approaches he may show a certain amount of bias to a degree towards the effectiveness and prevalence of some of these systems. Reviewing this article 16 years later places me in the unique position as to view some of these systems in present day to asses which of these concepts have been refuted and which concepts have come to fruition.
Langer states early in the introduction that the “Potential advantages of improved drug delivery systems include (1) continuous maintenance of drug levels in a therapeutically desirable range, (2) reduction of harmful side effects due to targeted delivery to a particular cell type or tissue. (3) Potentially decreased amount of drug needed. Langer goes on further to state that these advantages are important as up to $136 billion in health care costs in the USA are attributed to Adverse drug events”3. In modern times these costs have dropped considerably, “it is estimated that the cost of Adverse Drug Events in 2006 was 3.5 billion US dollars”4. This decrease in cost would suggest that in present times the previously mentioned advantages have somewhat been achieved with the use of improved drug delivery systems. Langer uses a solid illustration to describe the common polymeric drug delivery systems, the pictures used are somewhat simplistic however the description of each picture is extensive and relates to delivery systems that are being used at the time.
In relation to active targeting Langer talks about the addition of galactose to a HPMA copolymer drug conjugate this in turn targets the liver due to the asialoglycoprotein receptor. He states that these systems as well as HPMA taxol conjugates are in clinical trials. From present day research it was seen that in 2002 a study using HPMA-doxorubin-galactosamine to treat primary a secondary liver cancer had specific targeting towards the liver. This was confirmed using gamma camera imaging and iodine labelled analogue 5. Therefore it should be noted that these polymer systems are now prominent.
With regards to liposome based delivery systems Langer states that an area of intense investigation is the use of cationic liposome for gene therapy. “Gene therapy was only approved in 1990 and the human genome was not mapped until 2001”6 therefore gene therapy was still in the early stages of development. However the use of cationic liposomes in gene therapy is used widely today one such example can be found in a review article from 2010. A solution of cationic lipids, often formed with neutral helper lipids, can be mixed with DNA to form a positively charged complex termed a lipoplex. One such lipolex is N-[1-(2,3-dioleyloxy) propyl]-N,N,N-trimethylammonium chloride, or DOTMA which was one of the first synthesized and commercially available cationic lipids used for gene delivery”7.
In conclusion it has to be said that this article was very well written by Robert Langer the material provided is informative and with a basic knowledge of drug delivery it is easy to understand. The use of illustrations and subheadings make the article very descriptive and relevant for the time. Although this article was written in 1998 it is years ahead of its time. Robert Langer makes some closing points in the discussion section stating that progress in certain sectors will improve drug delivery such points include progress in immunology and human genomics which can achieve site specific delivery, advancement in combinatorial chemistry which will lead to the production of new bio materials and finally the development of mathematical models can predict delivery performance. These closing points are important as they look to the future of drug delivery. It is the influx of funding into these areas of science has led to many of these sectors rapid progression and I believe they will continue to grow in further years.
Bibliography
- Langer, R (1998).Drug delivery and targeting, Nature. .: Macmillan publishers. 5-10.
- Gregoiraidis G. Engineered Liposomes for drug delivery, progress and problems, trends biotechnol. 13, 527-537, 1997
- Classen D, C Pestotnik, S.L Evans, SR, Lloyd, J.F Burke, J.P. Adverse drug events in hospitalised patients,J. Ann Assoc 277, 301-306 (1997)
- Aspden P, Wolcott JA, Bootman JL, Cronenwett LR. Preventing Medication Errors: Quality Chasm Series, The National Academic Press, Washington, DC 2007.
- Muzykantov, V (2002). Biomedical Aspects of drug targeting. ,: Kluwer Academic publishers. 202.
- NIOH. (2003). http://www.genome.gov/11006943. Available: http://www.genome.gov/11006943. Last accessed 5 Nov 2014.
- Balazs,DA Godbey,Wt. (2011). Liposomes for Use in Gene Delivery.Journal of Drug Delivery. Volume 2011 (.), 12.
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