More comfort and efficiency

Biodegradable microspheres and ocular implants do away with injections inseveral treatments

Technological advances in the production of medicines has to search for solutions that are less aggressive and more effective in the absorption of drugs by the organism. In the developed countries, the pharmaceutical industry invests fortunes in the quest for therapeutic quality and more comfort to the patients. In Brazil, in spite of the small size of investments in this sector, examples of competence and of the mastery of technology are popping up, with results similar to those of the major multinational laboratories. This is the case of a patent filed last April with the National Institute of Intellectual Property (INPI) by the Federal University of Minas Gerais (UFMG), which registers the technique for encapsulating insulin in biodegradable microspheres (polymer compounds). This is how it will be possible for the medicine to be administered in aerosol form, like the little sprays used by those who suffer from asthma; it is a more agreeable way than the subcutaneous shots taken every day by type 1 diabetics that it replaces.

The encapsulation of insulin is a process carried out by the team of Professor Armando da Silva Cunha Júnior, from the Pharmacotechnics and Pharmaceutical Technology Laboratory of the School f Pharmacy at UFMG, in Belo Horizonte. The use of biodegradable polymers in the preparation of new medicines is also made by him in the ophthalmologic area. “We have developed implants, in the form of a stick to be installed in the hind part of the eye, which releases drugs for a few months, while the polymeric material is degraded in the organism”, Cunha Júnior explains. For the time being, researches with the ophthalmic implant are concentrated on medicines intended for treating uveitis. This disease was originally an inflammation of the uveal tract, made up of the iris, the ciliary body and the choroid (a membrane located in front of the retina), but the term has also been employed for inflammations in adjacent structures, such as the retina and the optic nerve.

Uveites can be caused by surgical or accidental traumas, by external microorganisms, or may arise secondarily, associated with diseases like tuberculosis, toxoplasmosis and others. The first step is to treat it with the conventional corticoid based eye drops. However, the majority of times, this practice does not generate any results, and it becomes necessary to make use of medicine orally or by intraocular injections. Besides being painful, this treatment hardly ever brings good results and is, in large measure, the cause of blindness.

Interests in innovation
Cunha Júnior is enthusiastic with the repercussion that this kind of ophthalmologic implant may have in the Brazilian pharmaceutical industry. “We have already made some contacts with Brazilian laboratories interested in developing the product”, he reveals. But the same is not happening with the insulin microspheres. “The problem is that there is no company in Brazil that is interested in transforming this innovation into a product”, says the professor. The research that he carried out was done with insulin given by Biobras – the only factory of this medicine in Brazil, located in Montes Claros, in the north of Minas Gerais -, which produces this hormone.

The tests were done on diabetic rats and mice, which responded well to the treatment with the encapsulated insulin. The next step would be to carry out clinical tests on humans, but there was not enough time. In February 2002, Biobras was sold to the pharmaceutical laboratory Novo Nordisk, from Denmark, and UFMG’s research was interrupted. “We believe that, with the sale of this Brazilian company, the prospects for marketing have disappeared. There is not at the moment, in Brazil, any interest in the encapsulated insulin, not least because we do not have any more a genuinely national company to produce the hormone and wants to develop here a new therapeutic method. Knowing the market as I do, I don’t have any hopes”, the researcher complains.

And he is talking as someone who knows. In the period between his graduation from the School of Pharmacy at UFMG, in 1986, and his postgraduate studies (for a master’s degree and a doctorate), in France, at Paris XI University, from 1993 to 1997, Cunha Júnior worked with insulin in its traditional form, at Biobras. It was at that time that he began to be interested in new pharmaceutical forms, the theme of his dissertation for a master’s degree and of his thesis for his doctor’s degree. In 1997, he received from the Association de Pharmacie Galénique Industrielle, or the Association of Galenic Industrial Pharmacy – Galenic meaning pharmacotechnics or pharmaceutical manipulation – and from the Association de Recherches Scientifiques Paul Neumann, or the Paul Neumann for Scientific Research Association – he was the founder of the old Hoechst laboratory, now bound up with Aventis, the prize for the best thesis on pharmaceutical technology prepared in France in that year.

The fact is that insulin in an aerosol will certainly arrive here, albeit imported. At the same time that the research was being carried on at UFMG’s School of Pharmacy, two small American high technology laboratories, the Inhale Therapeutics of San Carlos and the Aradigm Corporation, both from California, associated with the giants Pfizer and Aventis, were investing in similar research, which, with a few differences in the technological process, also resulted in the products as a base for an aerosol. The difference is that there the new format insulin is about to go onto the market.

Smaller doses
Even disillusioned with the current impossibility for insulin in an aerosol with Brazilian technology to reach the market, Cunha does not balk at pointing out the advantages of this new pharmaceutical form. He guarantees that the microencapsulation of insulin brings about the necessary protection for the stability of the hormone and facilitates its absorption by the organism. Moreover, it is more comfortable to apply and more effective in the treatment. “The pulmonary alveoli are extremely thin and permeable, making themselves a far easier barrier to overcome than the subcutaneous tissue. The doses can be smaller than those used subcutaneously, and the effect is more satisfactory”, the researcher explains.

The polymers used in the researches, known as PLGA, are derived from glycolic and lactic acids – the same raw material used to make biodegradable threads for stitches. In the work that led to the implant, another additional kind of technology was necessary. “In conjunction with UFMG’s Mechanical Engineering Department, we designed and built a prototype piece of equipment for compressing the powder containing a drug and a polymer, which is then molded into the format of a stick, 4 millimeters in length by 1 millimeter in diameter, which acts as a basis for an intraocular implant”, the researcher explains. The implant done in a minor surgical operation, when the biodegradable stick is put in the hind part of the eye. “Now, my hopes are concentrated on the ophthalmologic line.”

For the time being, the implants are being tested in rabbits, which show a similar eye structure to the human one, including their size. These studies are carried out in conjunction with the School of Medical Sciences of the University of São Paulo (USP), in Ribeirão Preto. The next step is to draw up a patent for this new therapeutic method as well.