Transdermal ve dermal terapötik sistemlerin diğer ilaç uygulama yollarına göre birçok avantajı bulunmaktadır. Transdermal yol, ilaçların oral yoldan verildiğinde ilk geçiş etkisi gibi mide-bağırsak sisteminde ortaya çıkabilecek sakıncaları önleyebilir, böylece ilaçların biyoyararlanımı artırır. Subkütan enjeksiyona göre daha düşük enfeksiyon riski ve maliyeti vardır. Hasta uyuncu daha yüksektir. Dermal uygulama ise ağrı ve sistemik yan etkileri en aza indirmesi ve kullanım kolaylığı gibi avantajlara sahiptir. Deriden ilaç geçişi hücre içi, hücreler arası, transapendageal ve gözenek yolu ile difüzyonla gerçekleşmektedir. Transdermal ve dermal sistemlerde karşılaşılan en büyük zorluklardan biri, ilaçların deriden geçişlerinin yeterli düzeyde olmamasıdır. Epidermisin en üst katmanı olan stratum korneum (SK), ilaç geçişine karşı engel özelliği göstermektedir. SK'nin hücre dışı lipid ile zenginleştirilmiş matrisi hidrofilik ilaçların geçişini sınırlamakta, lipofilik ilaçların ise birikip yavaşça salınmasına sebep olabilmektedir. Bu durum aktif bileşenlerin biyoyararlanımını düşürmektedir. İlaç taşıyıcı sistemlerin sağladığı avantajlardan faydalanarak, SK'nin engel işlevini aşmak için çeşitli aktif ve pasif yöntemler geniş çapta incelenmiştir. Bu derleme makalede de transdermal ve dermal terapötik sistemlerde ilaç geçişini artırma yöntemleri incelenmiştir. Birinci nesil transdermal ve dermal ilaç taşıyıcı sistemlerde ilaç geçişi çok sınırlıdır. Esas olarak ikinci nesil yöntemlerde ilaç geçişinin artırılması hedeflenmektedir. Bu kapsamda; ilaç-ilaç etkileşimi, SK modifikasyonu, ilaç taşıyıcı sistemler, enerji odaklı sistemler ve SK'nin atlatılması yöntemlerini içermektedir. İkincil nesildeki yöntemlerin birleştirilmesi ise üçüncü nesli oluşturmaktadır. Bu tür yenilikçi yaklaşımlar uygulanan ilaçları doz, maliyet ve terapötik etkinlik açısından daha avantajlı hâle getirebilir. Bu makale kapsamında özellikle ikinci nesil başlığı altında yer alan yöntemler özetlenerek, incelenmiştir.
Anahtar Kelimeler: Kutanöz uygulama; deri emilimi; iyontoforez; elektroporasyon; ilaç taşıyıcı sistem
Transdermal, dermal systems therapeutic systems have many advantages over other drug delivery routes. Transdermal route can prevent problems that may occur in gastrointestinal system such as first pass effect when the drugs are administered orally, increase bioavailability of drugs. It has lower infection risk, cost compared to subcutaneous injection. Patient compliance is higher. Dermal application has advantages such as minimizing pain, systemic side effects, ease of use. Drug passage through skin occurs by diffusion through intracellular, intercellular, transappendageal, pore routes. One of the biggest difficulties encountered in transdermal, dermal systems is insufficient penetration of drugs through skin. Stratum corneum (SC), uppermost layer of the epidermis, acts as barrier against drug penetration. Extracellular lipid-enriched matrix of SC restricts passage of hydrophilic drugs, causing accumulation, slow release of lipophilic drugs. This reduces bioavailability of active ingredients. Taking advantage of innovations in drug delivery systems, various active, passive methods have been extensively studied to exceed barrier function of SC. In this review article, methods of increasing drug penetration in transdermal, dermal therapeutic systems were examined. Drug pass is very limited in first generation transdermal, dermal drug delivery systems. It is aimed to increase drug pass in second generation methods. In this context; includes drug-drug interaction, SC modification, drug delivery systems, energy-focused systems, SC bypass methods. Combination of methods in second generation creates third generation. Such innovative approaches may make administered drugs more advantageous in terms of dose, cost, therapeutic efficacy. In this research article, especially methods under second generation title are summarized, examined.
Keywords: Cutaneous administration; skin absorption; iontophoresis; electroporation; drug delivery systems
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