Demet ENGİN, Selin Seda TİMUR, Stela MUÇAJ, R. Neslihan GÜRSOY

Opioid Peptidleri: Farmasötik Açıdan Önemi ve Formülasyon Yaklaşımları

Opioidler, kendi reseptörlerine bağlanarak gösterdikleri ağrı kesici etki nedeniyle, binlerce yıldır ağrı tedavisinde kullanılmaktadır. Günümüzde kullanımları daha kontrollü olarak hala devam etmektedir. Ancak yan etkileri ve bağımlılık potansiyelleri nedeniyle hastaların izlenmesi gerekmektedir. Araştırmacılar tarafından, insan vücudunda doğal olarak sentezlenen ve opioid benzeri etkilere yol açan endojen opioid peptidleri bulunmuştur. Bu peptidlerin sentetik analogları da sentezlenmektedir. Bu bileşikler kimyasal yapılarından dolayı hidrofiliktir, yük taşırlar ve oral olarak uygulanmaları kısıtlıdır. Bu nedenle formülasyon için farklı yaklaşımlar geliştirilmiştir. Peptid tabanlı hidrojel sentezlenmesi ve bileşiğin hidrojele konjuge edilmesi, peptidin kumarinik asit temelli siklik bir ön ilaca dönüştürülmesi yaklaşımları stabil olmayan opioid peptidleri enzimatik parçalanmadan korur. Peptidin bir nanopartiküle yüklenmesi ve lipozomal nanotaşıyıcıların kullanılmasında nanoteknolojiden yararlanılmıştır. Multiveziküler lipozomlar (DepoFoam) kullanılarak cerrahi sonrası ağrı yönetiminde peptid temelli ilaç uygulanması mümkündür. Opioid peptidler, tedavide faydalanılabilecek birçok endikasyona sahiptir. Peptidlerin formülasyonunda çok çeşitli teknolojiler kullanılmaktadır ve bu çalışmalardan umut verici sonuçlar elde edilmiştir.

Anahtar Kelimeler:

opioid, opioid peptid, opioid reseptör, formülasyon, lipozom

Opioid Peptides: Pharmaceutical Significance and Formulation Approaches

Opioids have been used in pain management for thousands of years due to the pain relief effects that they show by binding to their own receptors. Nowadays, their use continues in a more controlled manner because they have various side effects and a potential for dependence. Researchers have found substances that are naturally synthesized and cause opioid-like effects in the human body. These substances are known as endogenous opioid peptides. Synthetic analogs of these peptides are also synthesized. These compounds are hydrophilic due to their structure, they are charged molecules and their oral administration is limited. There are several approaches to the formulation of opioid peptides. Synthesis of peptide-based hydrogels and conjugation of the compound to a hydrogel, conversion of the peptide into a coumarinic acid-based cyclic prodrug are some of the approaches that protect unstable opioid peptides from enzyme degradation. Nanotechnology has also been used to encapsulate peptides in nanocarriers such as; nanoparticles and liposomes. In this context, research shows that it is possible to administer peptide-based drugs in post-surgical pain management using multivesicular liposomes (DepoFoam). A wide variety of technologies are used in the formulation of these peptides and promising results have been obtained from these studies.

Keywords:

opioid, opioid peptide, opoid receptor, formulation, liposome,

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