{"id":4508,"date":"2020-03-26T13:51:03","date_gmt":"2020-03-26T13:51:03","guid":{"rendered":"https:\/\/www.innovationnewsnetwork.com\/?p=4508"},"modified":"2020-04-01T14:26:09","modified_gmt":"2020-04-01T13:26:09","slug":"controlled-drug-delivery-working-on-new-options-for-better-therapies","status":"publish","type":"post","link":"https:\/\/www.innovationnewsnetwork.com\/controlled-drug-delivery-working-on-new-options-for-better-therapies\/4508\/","title":{"rendered":"Controlled drug delivery: working on new options for better therapies"},"content":{"rendered":"

Although the concept of controlled and local drug delivery is not new, there is an urgent need to improve existing systems and to explore new applications.<\/h2>\n

Professor Karsten M\u00e4der of Martin Luther University Halle-Wittenberg<\/a>, Germany, delves into the concept of controlled drug delivery.<\/p>\n

Our desire does not match reality<\/h3>\n

As a patient, we expect drug therapy<\/a> to be a fast cure without any side effects. Preferentially, we would like to take tablets, and avoid injections. Unfortunately, our desire does not match reality. Many drug molecules are not absorbed after oral ingestion. In addition to this, most of them have very short half-life\u2019s and therefore, repeated injections within a short time period or long lasting infusions are required. Important examples of such molecules are peptides, which are used to treat breast and prostate cancer<\/a>.<\/p>\n

One solution is the development of controlled release formulations. In the preferred scenario, a biodegradable drug delivery system releases the drug with constant velocity, leading to constant drug concentrations over a prolonged time period. Although controlled release formulations are on the market, many of them show undesirable release profiles, including high initial release (also known as \u2018burst release\u2019).<\/p>\n

For example, depot systems designed to deliver peptides over one month or three months, release more than 50% of the drug load within the first three days. For marketed controlled release, peptide formulations with much higher drug levels have been observed (<500 fold the necessary concentration). These numbers indicate the need for improved and alternative systems. In the area of schizophrenia, marketed formulations show a lag time (no initial release). The reason for the poor performance regarding the release kinetics are connected with the material properties of the biodegradable excipients.<\/p>\n

Currently, polylactide (PLA) and poly(lactide-co-glycolide) PLGA polymers are dominating the field. They degrade by hydrolysis to acidic monomers, which might lead to very acidic pH values (as low as pH2), degradation of drugs prior release, autocatalytic processes and nonlinear release kinetics. Therefore, the development of new biodegradable drug delivery systems (DDS) with constant release profiles is necessary to fully translate the high potential of controlled release into the best benefits for the patient\u2019s. Drug molecules do not know the location of the action. Their distribution is driven by the physico-chemical properties and the biological environment.<\/p>\n

In many cases, only a very low percentage of the applied dose reaches the disease related area, the majority is distributed to other tissues, causing side effects. For example, periodontitis requires often an antibiotic treatment. Oral ingestion of tablets or capsules requires high doses and causes serious side effects because of the harm and gut microflora. The rationale for local treatment inside the periodontal pocket is very clear, because by this approach, the following advantages can be achieved:<\/p>\n

    \n
  1. Reduction of overall dose;<\/li>\n
  2. Avoidance of side effects due to local release; and<\/li>\n
  3. Higher efficiency due to high local drug concentrations with decreased possibilities for resistance development.<\/li>\n<\/ol>\n

    The problem of low drug concentrations after systemic administration is evident in many organs, including the brain, the eye and the ear. Because of the increasing importance of eye and ear diseases due to an ageing society, new and better delivery systems are required to solve the unmet needs of drug therapy. This is exactly the main goal of the drug delivery research group around Prof Karsten M\u00e4der from the Martin Luther University Halle-Wittenberg, Germany. Making new combinations of already existing excipients or designing new materials, Karsten develops incorporation with his partners in chemistry, physics and medicine new biodegradable drug delivery systems. The following examples illustrate some recent achievements:<\/p>\n

    \"\"<\/a>
    L-R top row: \u00a9 Karsten M\u00e4der, \u00a9 iStock\/MedicalArtInc, \u00a9 iStock\/Eraxion, \u00a9 iStock\/yomogi1. L-R Bottom row: \u00a9 Karsten M\u00e4der, \u00a9 Karsten M\u00e4der, \u00a9 Karsten M\u00e4der, \u00a9 Karsten M\u00e4der<\/figcaption><\/figure>\n

    Local treatment of periodontitis<\/h3>\n

    In co-operation with partners from the Fraunhofer Institutes IMWS and IZI in Halle and the University Bern, M\u00e4der and his PhD-student Martin Kirchberg developed systems of treatment of periodontitis. With the formation of a lipophilic complex of known antibiotics and their extrusion with a biodegradable polymer matrix, they developed a new flexible extrudates with the following advantages compared to existing products:<\/p>\n