Oral mukozada görülen mantar enfeksiyonlarının lokal tedavisi için yeni biyoadezif dozaj şekillerinin geliştirilmesi ve ın vıtro / ın vıvo olarak değerlendirilmesi
Küçük Resim Yok
Tarih
2014
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Oral mukozada görülen mantar enfeksiyonları ya da diğer adıyla oral kandidiyasis, oral boşluklarda sıklıkla gözlenen ve ciddi komplikasyonlara sebep olabilen fırsatçı, mikotik bir enfeksiyondur ve her yaşta akut veya kronik olarak kendini göstermektedir. Son yıllarda kanser tedavisinin, yetersiz beslenmenin, geniş spektrumlu antibiyotik ve steroid kullanımının artması oral kandidiyazis olgularında artışa neden olmuştur. Oral kandidiyazisin en yaygın patojeni Candida türleridir. Konvansiyonel tedavide antifungal etkin maddelere bağlı olarak ortaya çıkan yan etkilerin çoğunlukla doza bağlı olması daha düşük dozla tedavinin gerçekleştirilebileceği lokal olarak uygulanabilecek ilaç şekillerine olan ihtiyacın artmasına sebep olmuştur. Çalışma kapsamında kullanılan flukonazolün oral kandidiyazis tedavisi için, Türkiye İlaç Piyasasında bukkal mukozaya lokal olarak uygulanabilecek bir preparatı bulunmamaktadır. Bu amaçla çalışmada biyoadezif nanopartikül, nanopartikül içeren in situ jel ve oral strip formülasyonları geliştirilmiştir. Hazırlanan tüm formülasyonların karakterizasyon çalışmaları yapılmıştır. Karakterizasyon çalışmaları sonucunda uygun olduğu düşünülen formülasyonların hücre kültürü çalışmalarıyla sitotoksisiteleri ve mikrobiyolojik çalışmalarla ise in vitro antifungal etkinlik çalışmaları saptanmıştır. Bu çalışmalar sonucunda en etkin formülasyonun N19 kodlu biyoadezif nanopartikül formülasyonu olduğu görülmüş ve in vivo antifungal çalışmalar gerçekleştirilmiştir. In vivo çalışmalarda, Candida albicans ile enfekte edilen tavşanlara, oral mukozada mantar oluşumundan sonra N19 kodlu formülasyon uygulanmış ve oral mukozadan alınan sürüntü örnekleriyle uygulanan tedavinin etkinliği izlenmiştir. In vivo çalışmalar oral mukozanın histolojik açıdan değerlendirilmesi ile sonlandırılmıştır. Sonuç olarak; bu tez çalışmasında, oral kandidiyazis tedavisi için sistemik uygulamaya alternatif olabilecek lokal flukonazol yüklü formülasyonlar geliştirilmiş, hasta uyuncu açısından uygulama sıklığı azaltılmış ve bu formülasyonların etkinliği in vitro, ex vivo ve in vivo koşullarda ispatlanmıştır
Oral mucosal fungal infection, or most commonly referred as oral candidiasis, is an opportunistic, mycotic infection of oral cavity that can lead to serious complications, and can be observed as an acute or chronic infection at any age. Recently, because of the increased rate of cancer treatment and malnutrition cases and soared use of wide spectrum antibiotics and steroids, the frequency of oral candidiasis have escalated, as well. It improves the risk of infection whose common pathogen is Candida species. Most of the adverse side effects observed in conventional antifungal therapy are dose related; therefore, an increasing need for topical preparations with lower effective doses which may be administered safely is emerging. In Turkish Drug Market, there isn't any local formulation of fluconazole for the treatment of oral candidiasis for application to buccal mucosa. For this aim; in the present study, bioadhesive nanoparticle, nanoparticle loaded in situ gel and oral strip formulations were developed. The characterizations of all prepared formulation were investigated. The cytotoxicities by cell culture studies and in vitro antifungal activity studies by microbiological studies were evaluated with formulations which selected according to characterization studies. These studies showed that the most effective formulation was N19 bioadhesive nanoparticle formulation and in vivo antifungal activity studies were performed. In in vivo tests, rabbits were inoculated with Candida albicans and infection was occured on oral mucosa. The infected rabbits were treated with local administration of N19 formulation. Buccal mucosal smears were collected in order to establish the clinical efficacy of the antifungal therapy. In vivo tests were finalized with histological examination of oral mucosa. Consequently, in this thesis, local fluconazole loaded formulations were developed for alternative to systemic therapy of oral candidiasis, frequency of administration was reduced in terms of patient compliance and the efficiency of these formulations were proved both in vitro, ex vivo and in vivo conditions.
Oral mucosal fungal infection, or most commonly referred as oral candidiasis, is an opportunistic, mycotic infection of oral cavity that can lead to serious complications, and can be observed as an acute or chronic infection at any age. Recently, because of the increased rate of cancer treatment and malnutrition cases and soared use of wide spectrum antibiotics and steroids, the frequency of oral candidiasis have escalated, as well. It improves the risk of infection whose common pathogen is Candida species. Most of the adverse side effects observed in conventional antifungal therapy are dose related; therefore, an increasing need for topical preparations with lower effective doses which may be administered safely is emerging. In Turkish Drug Market, there isn't any local formulation of fluconazole for the treatment of oral candidiasis for application to buccal mucosa. For this aim; in the present study, bioadhesive nanoparticle, nanoparticle loaded in situ gel and oral strip formulations were developed. The characterizations of all prepared formulation were investigated. The cytotoxicities by cell culture studies and in vitro antifungal activity studies by microbiological studies were evaluated with formulations which selected according to characterization studies. These studies showed that the most effective formulation was N19 bioadhesive nanoparticle formulation and in vivo antifungal activity studies were performed. In in vivo tests, rabbits were inoculated with Candida albicans and infection was occured on oral mucosa. The infected rabbits were treated with local administration of N19 formulation. Buccal mucosal smears were collected in order to establish the clinical efficacy of the antifungal therapy. In vivo tests were finalized with histological examination of oral mucosa. Consequently, in this thesis, local fluconazole loaded formulations were developed for alternative to systemic therapy of oral candidiasis, frequency of administration was reduced in terms of patient compliance and the efficiency of these formulations were proved both in vitro, ex vivo and in vivo conditions.
Açıklama
Anahtar Kelimeler
Eczacılık ve Farmakoloji, Pharmacy and Pharmacology, Jeller, Gels, Nanopartiküller, Nanoparticles
