An alternative evaluation method for swelling studies of bioadhesive tablet formulations

WOS: 000223659300001PubMed ID: 15458229A new and alternative evaluation method is preferred for swelling studies of bioadhesive tablet formulations. CIELAB color coordinates, related to visual color response, are used for the first time to follow the swelling state and to calculate the swelling volume. The results are evaluated statistically. A simple equation is given to explain the relation between the swelling volume change % and color difference for three different bioadhesive formulations. It was found that the estimated equation is in good agreement with observed swelling volume results

Gemcitabine hydrochloride microspheres used for intravesical treatment of superficial bladder cancer: a comprehensive in vitro/ex vivo/in vivo evaluation

Sinem Yaprak Karavana,1 Zeynep Ay Şenyiğit,2 Çağrı Çalışkan,3 Gülnur Sevin,4 Derya İlem Özdemir,2 Yalçın Erzurumlu,5 Sait Şen,6 Esra Baloğlu1 1Department of Pharmaceutical Technology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 2Department of Pharmaceutical Technology, Faculty of Pharmacy, Izmir Katip Çelebi University, Izmir, Turkey; 3Department of Radiopharmacy, Faculty of Pharmacy, Ege University, Izmir, Turkey; 4Department of Pharmacology, Faculty of Pharmacy, Ege University, Izmir, Turkey; 5Department of Biochemistry, Faculty of Pharmacy, Ege University, Izmir, Turkey; 6Department of Pathology, Faculty of Medicine, Ege University, Izmir, Turkey Introduction: Bladder cancer is responsible for more than 130,000 deaths annually worldwide. Intravesical delivery of chemotherapeutic agents provides effective drug localization to the target area to reduce toxicity and increase efficacy. This study aimed to develop an intravesical delivery system of gemcitabine HCl (Gem-HCl) to provide a sustained-release profile, to prolong residence time, and to enhance its efficiency in the treatment of bladder cancer. Materials and methods: For this purpose, bioadhesive microspheres were successfully prepared with average particle size, encapsulation efficiency, and loading capacity of 98.4 μm, 82.657%±5.817%, and 12.501±0.881 mg, respectively. For intravesical administration, bioadhesive microspheres were dispersed in mucoadhesive chitosan or in situ poloxamer gels and characterized in terms of gelation temperature, viscosity, mechanical, syringeability, and bioadhesive and rheological properties. The cytotoxic effects of Gem-HCl solution, Gem-HCl microspheres, and Gem-HCl microsphere-loaded gel formulations were evaluated in two different bladder cancer cell lines: T24 (ATCC HTB4TM) and RT4 (ATCC HTB2TM). Results: According to cell-culture studies, Gem-HCl microsphere-loaded poloxamer gel was more cytotoxic than Gem-HCl microsphere-loaded chitosan gel. Antitumor efficacy of newly developed formulations were investigated by in vivo studies using bladder-tumor-induced rats. Conclusion: According to in vivo studies, Gem-HCl microsphere-loaded poloxamer gel was found to be an effective and promising alternative for current intravesical delivery-system therapies. Keywords: gemcitabine HCl, intravesical chemotherapy, superficial bladder cancer microspheres, mucoadhesive gel, in situ ge

Design and evaluation of an intravesical delivery system for superficial bladder cancer: preparation of gemcitabine HCl-loaded chitosan–thioglycolic acid nanoparticles and comparison of chitosan/poloxamer gels as carriers

Zeynep Ay Şenyiğit,1 Sinem Yaprak Karavana,1 Derya İlem-Özdemir,2 Çağrı Çalışkan,2 Claudia Waldner,3 Sait Şen,4 Andreas Bernkop-Schnürch,5 Esra Baloğlu1 1Faculty of Pharmacy, Department of Pharmaceutical Technology, Ege University, Bornova, İzmir, Turkey; 2Faculty of Pharmacy, Department of Radiopharmacy, Ege University, Bornova, İzmir, Turkey; 3ThioMatrix, Forschungs-Beratungs GmbH, Innsbruck, Austria; 4Faculty of Medicine, Department of Pathology, Ege University, Bornova, İzmir, Turkey; 5Institute of Pharmacy, Department of Pharmaceutical Technology, University of Innsbruck, Innsbruck, AustriaAbstract: This study aimed to develop an intravesical delivery system of gemcitabine HCl for superficial bladder cancer in order to provide a controlled release profile, to prolong the residence time, and to avoid drug elimination via urination. For this aim, bioadhesive nanoparticles were prepared with thiolated chitosan (chitosan–thioglycolic acid conjugate) and were dispersed in bioadhesive chitosan gel or in an in situ gelling poloxamer formulation in order to improve intravesical residence time. In addition, nanoparticle-loaded gels were diluted with artificial urine to mimic in vivo conditions in the bladder and were characterized regarding changes in gel structure. The obtained results showed that chitosan-thioglycolic acid nanoparticles with a mean diameter of 174.5±3.762 nm and zeta potential of 32.100±0.575 mV were successfully developed via ionotropic gelation and that the encapsulation efficiency of gemcitabine HCl was nearly 20%. In vitro/ex vivo characterization studies demonstrated that both nanoparticles and nanoparticle-loaded chitosan and poloxamer gels might be alternative carriers for intravesical administration of gemcitabine HCl, prolonging its residence time in the bladder and hence improving treatment efficacy. However, when the gel formulations were diluted with artificial urine, poloxamer gels lost their in situ gelling properties at body temperature, which is in conflict with the aimed formulation property. Therefore, 2% chitosan gel formulation was found to be a more promising carrier system for intravesical administration of nanoparticles. Keywords: chitosan–TGA, nanoparticle, gemcitabine HCl, intravesical administration, chitosan, poloxamer, superficial bladder cance

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

Seda Rençber,1 Sinem Yaprak Karavana,1 Fethiye Ferda Yilmaz,2 Bayri Eraç,2 Merve Nenni,3 Seda Özbal,4 Çetin Pekçetin,4 Hande Gurer-Orhan,3 Mine Hoşgör Limoncu,2 Pelin Güneri,5 Gökhan Ertan11Faculty of Pharmacy, Department of Pharmaceutical Technology, 2Department of Pharmaceutical Microbiology, 3Department of Pharmaceutical Toxicology, Ege University, Bornova, Turkey; 4Department of Histology and Embryology, School of Medicine, Dokuz Eylul University, Inciralti, Turkey; 5Faculty of Dentistry, Department of Oral Diagnosis and Radiology, Ege University, Bornova, TurkeyAbstract: 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.Keywords: mucoadhesive nanoparticle, buccal application, oral candidiasis, fluconazole, chitosa