Tip 2 diabetes mellitus, dünya genelinde yaygın olarak görülen dejeneratif ancak kontrol altında tutulabilir önemli bir sağlık sorunu olup, yaşam boyu sürecek tedavi yönetimi gerektirmektedir. Yaşam kalitesini en fazla etkileyen kronik hastalıklardan biri olarak kabul edilmekte ve ciddi bir tıbbi, sosyal ve ekonomik tehdit oluşturmaktadır. Geleneksel oral antidiyabetik ilaçlar hem biyoyararlanım ve dozaj yönetimi açısından hem de hasta uyuncu ve tedavinin etkililiği açısından dezavantajlara sahip olabilmektedir. Bu bağlamda geliştirilmekte olan transdermal ilaç formülasyonları, diyabet tedavisinde yeni bir perspektif sunmaktadır. İnkretin bazlı etki gösteren dipeptidil peptidaz (DPP)- 4 enzim inhibitörleri; sitagliptin, saksagliptin, linagliptin, alogliptin ve vildagliptin olarak sıralanabilir. DPP-4 inhibitörleri, glukagon benzeri peptid-1 (GLP-1) ve gastrik inhibitör polipeptid (GIP) gibi endojen inkretinlerin konsantrasyonunu ve aktivitesini artırıp bu hormonların DPP-4 tarafından proteolitik parçalanmasını engelleyerek etki gösterir ve bunları aktif olmayan moleküllere dönüştürür. Aktif GLP-1 ve GIP seviyesindeki artış, glukozla uyarılmış insülin salgısını potansiyalize eder. DPP-4 inhibitörlerinin oral uygulamalarının sınırlamaları, transdermal formülasyonların geliştirilmesine zemin hazırlamıştır. Bu derlemenin amacı, DPP-4 inhibitörleri kullanılarak hazırlanan transdermal formülasyonlara odaklanarak, hazırlanan transdermal formülasyonların diyabet tedavisindeki potansiyel avantajlarını incelemektir. DPP-4 inhibitörleri kullanılarak hazırlanan transdermal formülasyonların formülasyon ajanları ve metodu, salım profilleri, oral kullanıma kıyasla sağladıkları avantajlar detaylı bir şekilde ele alınmış. DPP-4 inhibitörlerinin transdermal kullanımına ilişkin son gelişmeler incelenerek gelecekteki potansiyel araştırma alanları vurgulanmıştır.
Anahtar Kelimeler: Transdermal yama; dipeptidil-peptidaz IV inhibitörleri; diabetes mellitus; Tip 2
Type 2 diabetes mellitus is a degenerative but controllable worldwide health issue, requiring lifelong treatment management. It is considered one of the chronic diseases that most significantly affects quality of life and poses a serious medical, social and economic threat. Traditional oral antidiabetic drugs may have disadvantages in terms of bioavailability and dosage management, as well as patient compliance and effectiveness of treatment. In this context, developing transdermal drug formulations offers a new perspective in diabetes treatment. Incretin based dipeptidyl peptidase (DPP)-4 enzyme inhibitors can be listed as sitagliptin, saxagliptin, linagliptin, alogliptin and vildagliptin. DPP-4 inhibitors increase the concentration and activity of endogenous incretins such as glucagonlike peptide 1 (GLP-1) and gastric inhibitory polypeptide (GIP), inhibiting their proteolytic breakdown by DPP-4 and converting them into active molecules. Increased levels of active GLP-1 and GIP potentiate glucose-stimulated insulin secretion. The limitations of oral administration of DPP-4 inhibitors have paved the way for the development of transdermal formulations. The aim of this review is to focus on transdermal formulations prepared using DPP-4 inhibitors and examine the potential advantages of these formulations in diabetes treatment. Formulation agents and methods, release profiles and advantages of transdermal formulations prepared using DPP-4 inhibitors compared to oral use are discussed in detail. Recent developments regarding the transdermal use of DPP-4 inhibitors are reviewed and potential areas for future research are highlighted.
Keywords: Transdermal patch; dipeptidyl-peptidase IV inhibitors; diabetes mellitus; Type 2
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