Перспективи застосування модифікацій пектину в комплексі медикаментозної терапії раку товстої кишки

Abstract

Альтернативою парентеральному введенню хіміотерапевтичних препаратів при лікуванні хворих на колоректальний рак все частіше застосування лікарських форм для перорального прийому. У такий спосіб можна досягнути зменшення дози лікарських препаратів та системних побічних ефектів. Враховуючи, що специфічна мікрофлора товстого кишечника вибірково перетравлює пектин, останній може бути використаний в якості специфічного засобу для локальної доставки лікарських середників, запобігаючи їх вивільненню у верхніх відділах шлунково-кишкового тракту. Пектин розглядають не тільки як носій лікарського засобу, але і в якості терапевтичного агента в лікуванні і профілактиці колоректального раку; Альтернативой парентеральному введению химиотерапевтических препаратов при лечении больных колоректальным раком все чаще становится применения лекарственных форм для перорального приема. Таким образом можно достичь уменьшения дозы лекарственных препаратов и системных побочных эффектов. Учитывая, что специфическая микрофлора толстого кишечника выборочно переваривает пектин, последний может быть использован в качестве специфического средства для локальной доставки лекарственных средств, предотвращая их высвобождение в верхних отделах желудочно-кишечного тракта. Пектин рассматривают не только как носитель лекарственного средства, но и в качестве терапевтического агента в лечении и профилактике колоректального рака; Colorectal cancer is one of the most common cancer globally. It occupy the fourth place in the structure of total cancer incidence. The basic treatment for colon cancer is surgery combined with chemotherapy or radiotherapy. Usually chemotherapy is provided by injection route. Alternative to the usual chemotherapy might be oral intake of chemotherapeutic agents. In this way can be achieved the reduce of drug dose, systemic side effects and increased efficiency. In general, 5 technologies for the specific delivery of drugs to the colon have been developed. All of them have a common concept that involves the use of physiological features of the gastrointestinal tract to provide activation and release of drugs to achieve colon. Among them: azo-polymer system, pH, pressure- and time-dependent systems, as well as delivery systems based on the activity of the colon microflora. Pectin can be used as colon-specific drug delivery agent, because colonic microflora can selectively digest it. So this leads to the prevention of drug release in the upper gastrointestinal tract. Unlike insoluble cellulose fibers, it undergoes almost 100% fermentation in the colon, leading to the formation of short-chain fatty acids, which are the main source of energy for colon cysts. In addition, short-chain fatty acids can suppress proliferation and promote tumor cell apoptosis in vitro and in vivo, and because of lowering the pH of the colon, they reduce the formation of secondary bile salts, impede the activity of 7-α-dehydroxylase, and reduce the solubility of free bile acid, showing account of the indicated properties anti-carcinogenic effect. Therefore pectin can be considered not only as drug carrier but also as therapeutic agent for use in the prevention and acting against colorectal cancer. The pectin-based matrices are developed in the form of a unit dose, as well as in a multi-dosage form: granules, pills, microparticles. To prevent the premature release of drugs from the pectin matrix in the upper gastrointestinal tract, the researchers were subjected to the last transverse coupling of di- and multivalent cations, coaccessing with an oppositely charged electrolyte, mixing with a viscous polymer and/or calcium salt, or coated by pH-resistant and weakly soluble polymer. Pectin, in combination with a crosslinking agents or polymers, can be used on the nucleus of the drug surface as a suppressive releasing membrane in the form of a film or applied by compression technology. In particular, a multi-layer coating on the core of the drug may be used, with the layers having different chemical composition to slow down/modulate the release of drugs in various locations of the upper gastrointestinal tract. Currently many researchers are trying to create a pectin dosage form for the delivery of drugs with delayed releasing effect. Gelatin, alginate and xyloglucan are just some of the polymers used in the formulation of pectin delivery systems. Thus, the analysis of the current literature data determined that further in-depth study of the pectin properties and an assessment of the link between its structure and capabilities in the aspect of creating a colon-specific drug delivery system are relevant and promising. The combined efficacy of pectin as a drug and/or therapeutic enhancer in delivering colon-specific anti-cancer drugs requires extensive testing in the clinic to confirm it. Creating a pectin dosage form of drug delivery to the colon, acting exclusively and precisely at the site of colorectal cancer is a challenge for pharmacists and oncologists.