Erythrocytes as carriers for drugs: the transition from the laboratory to the clinic is approaching

Abstract

Erythrocytes have been suggested to be smart carriers for drugs, biologics and other therapeutic agents, and a paper in the present issue of the journal confirms the wide interest and the expectations the technology has generated. In this Editorial, I briefly summarize the advances in the field and try to figure out the process that will take this technology to the clinic. The conclusion is that, after several years of basic research, the time is fast approaching since two companies in Europe are actively engaged in industrializing the process and searching approval for treatments with structured clinical trials.

Keywords:

• carrier erythrocytes
• drug delivery
• translational medicine

1. Erythrocytes as carriers for drugs

Almost four decades ago, Ihler and coworkers reported the first successful encapsulation of an enzyme into erythrocytes [1] to be potentially useful in enzyme replacement therapy. The principle was quite simple and was based on the unique properties of the erythrocytes to be reversibly opened under hypotonic conditions without losing their functionalities. When the cells are transiently opened, exogenous substances could be added and encapsulated upon resealing of the membrane pores. Since then, several hundreds of papers have described the use of erythrocytes as carriers for drugs, biologics, nanomaterials, contrasting agents and other agents useful as therapeutics or diagnostics (for selected reviews see [2-4]). Two main strategies, both posed for industrial development and clinical testing, are encapsulation of drugs into the resealed erythrocytes [5] and coupling of drugs to the surface of circulating erythrocytes [6,7]. Most of the interested readers frequently ask when this fascinating technology will become clinical practice, being smart, safe and of proved efficacy in a number of preclinical and clinical investigations. In addition, evident benefits for the treated patients have been documented (reduced number of side effects, reduced number of hospitalizations, etc.). Furthermore, by using this technology, the pharma companies could give new life to drugs with expired patents and the health services will probably save in the costs incurred by managing the most critical patients. The most easy answer to this question is that the transition from the laboratory to the clinic requires an industrialization process that should fit into established companies' business models or should start up with the support of venture capitals and motivated entrepreneurs. Until recently, most pharma companies were actively engaged in searching new blockbuster drugs and only recently, with the transition to a business model defined Pharma 3.0 [8], complementary approaches are actively pursued and considered with more attention. Thus, it is expected that the big pharma companies now become involved in these activities. In fact, the use of erythrocytes as carriers for drugs requires complementary competences usually distributed among pharma companies, medical devices firms, the communities of the patients and lastly an organization model that involves the clinic where the treatment is performed, and not simply an out-clinic setting. To overcome these limitations and speed up the process, recently two new companies have been established in Europe, namely Erytech Pharma in France (www.erytech.com) and EryDel in Italy (www.erydel.com). Both companies are already in the clinic and have received the designation of orphan drug for some of the products under development. The January issue of this journal includes the Meeting Highlights paper ‘International Seminar on the Red Blood Cells as Vehicles for Drugs’ [9], which reports additional results obtained at the clinical and preclinical levels and again emphasizes the potential of the approach. Several summarized data are updates of activities already published or familiar to experts in the field, but merit attention since it documents progress and limits of a technology that, although discovered many years ago, is still in its infancy and requires the enlargement of a scientific and clinical community to express all its potential. It is worth noting that the slow transition from the laboratory to the bed of the patient is now reaching the last stage of development and the accumulation of clinical data will certainly contribute to providing an answer to the readers about when it will be in the clinic. The answer is that we are very close, and the next few years will certainly see some of the applications approved by the regulatory authorities and become available to the whole community of the patients and no longer only to those that are entered into the several clinical trials so far performed.

2. Expert opinion

Drug delivery by erythrocytes is an established technology proved to be safe, effective and of benefit to the patients at preclinical and clinical levels. The technology has not yet reached the market, probably because the competences and skills required are usually distributed among different players. Most recently, the technology has been implemented at the industrial level by two European companies – Erytech Pharma and EryDel – that have finally addressed all the issues that concern the medical device (to encapsulate the therapeutic agent), the drug to be encapsulated and the clinical trials to be performed for regulatory approval of the treatment.

It is also worth noting that two designations of orphan drug have been granted to treatments that involve the use of erythrocyte as carriers, suggesting that the area of rare diseases is of special interest and a priority in the development of new applications.

It is expected that the technology is now moving faster than in the past and finally the patients could benefit from the advantages that have been experienced in several clinical trials reducing side effects and improving efficacy of conventional and new drugs.

Declaration of interest

The author owns shares in EryDel SpA.