Journal of Literature Pharmacy Sciences

Nanopartiküler İlaç Taşıyıcı Sistemler ile Oral İnsülin Tedavisinde Son Gelişmeler: Sistematik Derleme
Recent Advances in Oral Insulin Therapy by Nanoparticulate Drug Delivery Systems: Systematic Review
Tuğçe TURANa, N. Başaran MUTLU AĞARDANa
aGazi Üniversitesi Eczacılık Fakültesi, Farmasötik Teknoloji ABD, Ankara, Türkiye
J Lit Pharm Sci. 2022;11(2):104-18
doi: 10.5336/pharmsci.2021-87457
Article Language: TR
Full Text
ÖZET
Diabetes mellitus, yüksek kan glukoz seviyeleri ile karakterize kronik, metabolik bir hastalıktır. Tedavisinde kullanılan en önemli molekül insülindir. İnsülin, pankreasın Langerhans adacıklarının β hücreleri tarafından üretilen, kan glukoz seviyesini düzenleme etkisini monomerik formunun insülin reseptörüne bağlanmasıyla gösteren bir hormondur. İnsülin vücuda subkütan yoldan verilmektedir fakat bu yol ile hasta uyuncu oldukça düşüktür. Ayrıca subkütan uygulama, enjeksiyon bölgesinde lipodistrofiye, alerjik reaksiyonlara ve enfeksiyona neden olmaktadır. İnsülin oral yol ile uygulandığında gastrointestinal (Gİ) kanalda proteolitik enzimler ile hızla parçalanmakta, yapısı dolayısıyla da düşük absorpsiyon göstermektedir. İnsülinin Gİ kanalda parçalanmasını önlemek ve oral biyoyararlanımını artırmak için birçok çalışma yapılmakta; bu çalışmalar nanopartiküler ilaç taşıyıcı sistemler üzerinde yoğunlaşmaktadır. Doğal (kitosan, aljinat, dekstran) veya sentetik (poli-laktik-ko glikolik asit, poli-laktik asit) polimerler ile hazırlanan nanopartiküllerin; çözünürlük artırma, modifiye salım sağlama, emilimi artırma ve oral biyoyararlanımı iyileştirme gibi pek çok faydası bulunmaktadır. İnsülin taşıyan bir nanopartiküler sistemin, insülini mide asidinden ve proteazlardan koruması, Gİ kanalda kalış süresini uzatması ve absorpsiyonunu artırması beklenir. Bu amaçla, nanopartiküler ilaç taşıyıcı sistem formülasyonlarına, insülinin bağırsak absorpsiyonunu artırmak için absorpsiyon artırıcılar, insülinin proteazlarla parçalanmasını engellemek için enzim inhibitörleri ilave edilebilir. Ayrıca insülinin midede parçalanmasını engellemek için enterik kaplama yapılabilmektedir. Bu derlemede diyabet hastalığı, insülin ve insülinin oral yoldan verilmesiyle ilgili kısaca genel bilgiler verilerek, insülin yüklü nanopartiküler ilaç taşıyıcı sistemler ile ilgili güncel literatür örneklerine odaklanılmıştır.

Anahtar Kelimeler: Diabetes mellitus; oral uygulama; ilaç taşıyıcı sistem; nanopartikül; insülin
ABSTRACT
Diabetes mellitus is a chronic, metabolic disease characterized by high blood glucose levels. The most important molecule used in its treatment is insulin. Insulin is a hormone produced by the β cells of the islets of Langerhans of the pancreas, which shows its blood glucose level regulation effect by binding its monomeric form to the insulin receptor. Insulin is applied subcutaneously, but patient compliance is very low by this route. In addition, subcutaneous administration causes lipodystrophy, allergic reactions and infection at the injection site. When insulin is administered orally, it is rapidly degraded by proteolytic enzymes in the gastrointestinal (GI) tract, and has low absorption due to its structure. Many studies are carried out to prevent the degradation of insulin in the GI tract and to increase its oral bioavailability; these studies focus on nanoparticular drug delivery systems. Nanoparticles prepared with natural (chitosan, alginate, dextran) or synthetic (poly-lactic-co-glycolic acid, poly-lactic acid) polymers, have many benefits such as increasing solubility, providing modified release, increasing absorption and improving oral bioavailability. An insulin-encapsulated nanoparticular system is expected to protect insulin from both harsh acidic conditions of stomach and degradation by proteases, prolong its residence time in the GI track and enhance its intestinal uptake. Nanoparticulate systems can also be formulated using penetration enhancers to increase intestinal penetration of insulin and enzyme inhibitors to inhibit the insulin degradation by proteases. Furthermore, enteric coating could be applied to prevent the breakdown of insulin in the stomach, In this review, brief general information about diabetes, insulin and oral administration of insulin is presented and recent literature about insulin loaded nanoparticulate drug delivery systems is focused on.

Keywords: Diabetes mellitus; oral administration; drug delivery system; nanoparticle; insulin
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4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com