Development, characterization, and in vivo assessment of mucoadhesive nanoparticles containing fluconazole for the local treatment of oral candidiasis

This study aimed to develop a suitable buccal mucoadhesive nanoparticle (NP) formulation containing fluconazole for the local treatment of oral candidiasis. The suitability of the prepared formulations was assessed by means of particle size (PS), polydispersity index, and zeta potential measurements, morphology analysis, mucoadhesion studies, drug entrapment efficiency (EE), in vitro drug release, and stability studies. Based on the optimum NP formulation, ex vivo drug diffusion and in vitro cytotoxicity studies were performed. Besides, evaluation of the antifungal effect of the optimum formulation was evaluated using agar diffusion method, fungicidal activity-related in vitro release study, and time-dependent fungicidal activity. The effect of the optimum NP formulation on the healing of oral candidiasis was investigated in an animal model, which was employed for the first time in this study. The zeta potential, mucoadhesion, and in vitro drug release studies of various NP formulations revealed that chitosan-coated NP formulation containing EUDRAGIT(®) RS 2.5% had superior properties than other formulations. Concerning the stability study of the selected formulation, the formulation was found to be stable for 6 months. During the ex vivo drug diffusion study, no drug was found in receptor phase, and this is an indication of local effect. The in vitro antifungal activity studies showed the in vitro efficacy of the NP against Candida albicans for an extended period. Also, the formulation had no cytotoxic effect at the tested concentration. For the in vivo experiments, infected rabbits were successfully treated with local administration of the optimum NP formulation once a day. This study has shown that the mucoadhesive NP formulation containing fluconazole is a promising candidate with once-a-day application for the local treatment of oral candidiasis

The Immunohistochemical Evaluation of Kidney An Experimentally Induced Hypertensive And Diabetic Rat Model

AMAÇ: Bu çalışmada, deneysel olarak ayrı ayrı ve birlikte diyabet ve hipertansiyon modeli oluşturulan sıçanlarda, lipoik asidin hipertansif ve diyabetik böbrek üzerindeki tedavi edici/hasar önleyici etkisinin araştırılması amaçlandı. YÖNTEMLER: Çalışmamızda Wistar cinsi ratlar 8 gruba ayrıldı (n=7). I. grup; Kontrol, II. Grup; Diabetes Mellitus, III. grup; 5/6 Nefrektomi, IV. Grup; Lipoik asit, V. Grup; 5/6 Nefrektomi+Diyabet, VI. grup, Diyabet+Lipoik asit VII. Grup; 5/6 Nefrektomi+Lipoik asit ve VIII. Grup; 5/6Nefrektomi+Diyabet+Lipoik asit. Diyabet modeli 45mg/kg STZ enjeksiyonu ile oluşturuldu ve hipertansiyon modeli için 5/6 nefrektomi modeli uygulandı. dl-α-Lipoik asit 30mg/kg/gün olacak şekilde 8 hafta oral gavaj yöntemi ile deneklere uygulandı. Böbrek dokuları rutin ışık mikroskobik doku takip işlemlerinden geçirilip parafin bloklara gömüldü. İmmünohistokimyasal olarak AT1 (Anjiyotensin II tip I reseptörü), VEGF (Vasküler Endotelial Büyüme Faktörü) ve ET1 (Endotelin 1) antikorları işaretlendi. BULGULAR: Diyabet ve nefrektomi modellerinin ayrı ayrı ve birlikte uygulandığı deneysel gruplarda (Grup 2, 3, 5), glomerüloskleroz, mononükleer hücre infiltrasyonu, intersitisiyel fibrozis, damarlarda ve tübüllerde dilatasyon ve hiyalin materyal birikimi ile tübüler yapıların dejenerasyonu gözlendi. Aynı gruplarda tübülointersitisiyel ve glomerüler AT1 azalırken, VEGF ve ET1 artış göstermişti. Lipoik asit tedavi gruplarında ise AT1'de artış, VEGF ve ET1'de ise Kontrol ve Lipoik asit grubuna benzer şekilde azalma gözlendi. SONUÇ: Diyabet ve hipertansiyonun birlikte gözlenmesinin böbrek hasarının hızlı ilerlemesine neden olduğu, lipoik asidin bu hastalıklara karşı böbrek üzerinde tedavi edici etkisinin olduğu sonucuna varıldı. OBJECTIVE: In this study, experimental diabetes and nephrectomy have been applied separately and together in order to investigate possible therapeutic/damage prevention effects of Lipoic acid on hypertensive and diabetic rat kidneys. METHODS: Wistar rats were divided into 8 groups (n=7); Group 1; Control, Group 2; Diabetes Mellitus, Group 3; 5/6 Nephrectomy, Group 4; Diabetes Mellitus+5/6 Nephrectomy, Group 5; Lipoic acid administration, Group 6; Diabetes Mellitus+Lipoic acid, Group 7; 5/6 Nephrectomy+Lipoic acid, Group 8; Diabetes Mellitus+5/6 Nephrectomy+Lipoic acid groups respectively. Diabetes was formed by 45mg/kg STZ injection and for hypertension nephrectomy 5/6 model was applied. dl-α-Lipoic acid 30mg/kg/day was fed by oral gavage for 8 weeks. Kidney tissues were embedded into paraffin block after routine light microscopic preparation. AT1 (Angiotensinojen II type 1 receptor), VEGF (Vascular Endothelial Growth Factor) and ET1 (Endothelin) antibodies were labelled immunohistochemically in same group. RESULTS: In groups where diyabetes and nephrectomy were applied separately and together, glomerulosclerosis, mononuclear cell infiltration, interstitial fibrosis, vascular and tubular dilatation and hyalin deposition and degeneration of tubular structures were seen in glomerules. In the same group: tubulointerstitial and glomerular AT1 was decreased but VEGF and ET1 were increased. In Lipoic acid treatment groups, AT1 was increased and VEFG and ET1 were decreased similar to Control and Lipoic acid group. CONCLUSION: We have come to the conclusion that diabetes nd hypertension together increases the rate of renal injury and lipoic acid has therapeutic effect on kidney

HAFİF ŞİDDETTE AYAK ŞOKU STRESİNİN PREFRONTAL KORTEKSTE ANTİOKSİDAN ENZİMLER VE LİPİD PEROKSİDASYONUNA ETKİSİ

DOPAMİNİN MONOAMİN OKSİDAZ TARAFINDAN METABOLİZMA EDİLMESİ SIRASINDA HİDROJEN PEROKSİT OLUŞUR