Device to Cure Retinoblastoma

Universidad de Buenos Aires - Facultad de Farmacia y Bioquímica

October 17, 2011 | 6 ′ 38 ′′


Device to Cure Retinoblastoma


An interdisciplinary team of researchers developed and tested with encouraging results, a polymeric device which is implanted in the lower part of the eye and frees in a selective way a chemotherapeutic drug. The development opens promising horizons in the treatment of retinoblastoma, a kind of ocular cancer which mainly affects children of up to two years old.

The polymeric device designed by the researchers measures 7 millimeters and avoids that the drug used to cure retinoblastoma is spread to undesired zones and which acts only over the tumor. The stages of study in an original animal model concluded successfully and nowadays the scientists are preparing new implants which permit the use in humans in the near future.

Retinoblastoma is a malignant tumor generated into the eye, in the retina. It is typical of the developing retina’s cells and that is why it is presented in general in children. Although it is suspected that it can start during breastfeeding, as it has an initially silent development, the most frequent is that it is diagnosed when the children are around two years old. “It is a cancer with very low or almost null level of mortality. In fact, with the enucleation of the affected eye it can be cured. But the objective is to avoid this end”, said to InfoUniversidades Dr. Guillermo Chantada, physician of the Hemato-Oncology Service of the Hospital Juan P. Garrahan.

Chemotherapy is the strategy used to reduce the volume of the tumors generated by intraocular retinoblastoma when children affected by the disease do not respond to conventional therapies, less aggressive. But systemic chemotherapy, which is injected intravenously, although it results efficient to reduce the tumor’s size it unchains adverse side effects which can even reach the development of fatal leukemia given the high levels of toxicity of the drugs used. It can be added the consequences of all kinds which chemotherapy causes in children the in general are some months or up to two years old.

It is estimated that around a 40 percent of the cases can have genetic origin, that is why it is fundamental to be cautious when there are family antecedents. But also, the eye tumor might develop after a spontaneous mutation of the retina’s cells. In these cases the causes are still being discussed. So, there is the coexistence of hypothesis which propose the effect of a virus, against those which remark the adverse action of some environmental agents and even the incidence of malnutrition.

In the first place, the researchers designed an original animal model with rabbits. In the tests to reduce the volume of the tumor it has been proved the systemic chemotherapy with topotecan, the chemotherapy agent chosen for these cases. Facing the undesired amount of side effects this has, we tried a more controlled strategy: the periocular administration of topotecan, which consisted in injecting the drug directly in the rabbit’s eye.

Although the periocular administration of topotecan presents sensitive advantages if it is compared with systemic chemotherapy, certain levels of the drug still pass to the bloodstream. Consequently, there can be measured and detected the plasmatic levels that the drug presents, which is equivalent to say that the drug is distributed to the whole organism. That is why the researchers decided to test a polymeric device which is implanted in the eye.

The production of the episcleral implant was in charge of the subjects Pharmacotechnia I and II. “To elaborate it we used a plastic material, a synthetic origin biocompatible polymer. The process of fabrication is relatively simple and consists in putting a polymer and the drug which are homogeneous mixtures, in a matrix. Then it is taken to a stove at 70 degrees, which permits the material to melt. Then it is cooled during half an hour at 4 degrees”, said Dr. Diego Chiappetta.

The result is a pill of seven millimeters diameter which has one of its faces covered to prevent that the drug is distributed to undesired zones and that the drug is only freed to the tumor. The pill is implanted in the lower part of the sick eye by means of an incision in the conjuntival tissue and the non-covered part is put towards the sclera.

The researchers studied exhaustively the selective liberation of the topotecan to the different eye tissues and observed much lower levels of the drug in the other eye (the unaffected by the tumor) than those registered with the periocular administration. So, it could also be noticed that the plasmatic levels of topotecan are notably lower if they are compared to those generated by the periocular administration and practically worthless regarding those registered after the application of the systemic chemotherapy.

For the first stage of the work it was key the contribution of the pharmacologists belonging to the ININFA and to the subject Pharmacology of the School of Pharmacy and Biochemistry, who made studies of doses and toxicity, among other preclinical and clinical pharmacokinetic studies. “Besides, we developed special microdialysis cannulas, a tool which permitted to measure continuously the levels of drug in test, without the need to practice successive punctures in the eye of the experimental animals”, remarked Dr. Guillermo Bramuglia.

The interdisciplinary team which developed and tested the periocular device is formed by members of the services of Hemato-Oncology, Ophthalmology and Pathology of Hospital Garrahan; of the subjects of Pharmacology and Pharmacotechnia of the School of Pharmacy and Biochemistry; and the Institute for Pharmacological Investigations (ININFA), depending on the Conicet. The link between all the areas was Dr. Ángel Montero Carcaboso from the Ministry of Education and Science in Spain. The well-known expert American researcher David Abramson, from the service of Ophthalmological Oncology, Memorial Sloan-Kettering Cancer Center in New York also participated.



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