Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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Author: search.filters.author.Celebi, Nevinsearch.filters.applied.f.language: search.filters.language.eng

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    A New Nanosuspension Prepared With Wet Milling Method For Oral Delivery Of Highly Variable Drug Cyclosporine A: Development, Optimization And In Vivo Evaluation
    (2022) Pinar, Sila Gulbag; Canpinar, Hande; Tan, Cagman; Celebi, Nevin; 35017012
    Cyclosporine A (CsA) is a cyclic polypeptide, that has been widely used for immunosuppression. This study aims to develop nanosuspension for oral administration of CsA using the wet milling (WM) method one of the top down technologies. The WM method was optimized by studying the effects of critical process parameters for WM on the particle size (PS), particle size distribution (PDI), and zeta potential (ZP) of nanosuspensions using the Design of Experiment (DoE) approach. Nanosuspension was developed using hydroxypropyl methylcellulose (HPMC) and sodium dodecyl sulfate (SDS) and in vitro characterization studies were performed. In vitro dissolution and in vivo pharmacokinetic studies were conducted with biorelevant media (fasted and fed state simulated fluids) and fasted and fed states in rats, respectively. In vivo immunological studies were also performed. PS, PDI, and ZP values for nanosuspension were approximately 600 nm, 0.4,-25 mV, respectively. The solubility of CsA was increased by 4.5-folds by nanosuspensions. Dissolution studies showed that nanosuspension had higher dissolution than the commercial product in the FeSSIF medium. The pharmacokinetic study indicated that AUC0(-24) values of CsA nanosuspension were to be 2.09 and 5.51-fold higher than coarse powder in fasted and fed conditions, respectively. Immunological studies were carried out after oral administration of nano suspension for 21 days, the ratio of CD4+/CD8+ was found to be more acceptable than the commercial product. These results demonstrated that nanosuspension is a promising approach for increasing the bioavailability and avoiding the food effect on absorption of CsA which one of the highly variable drugs.
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    Evaluation of Caco-2 cell permeability of ritonavir nanosuspensions
    (2020) Karakucuk, Alptug; Ozturk, Naile; Celebi, Nevin
    Background and Aims: Poor aqueous solubility limits drug absorption through intestinal mucosa. Nanosuspensions with nanometer range particle size provides enhanced aqueous solubility and hence permeability. The objective of this study was to investigate the cytotoxicity and in vitro cell permeability through human adenocarcinoma (Caco-2) cells of ritonavir (RTV) nanosuspensions. Methods: The Microfluidization method was used to prepare nanosuspensions. Particle size (PS), polydispersity index (PI) and zeta potential (ZP) values were measured as characterization. MTT test was applied to evaluate the cytotoxic effect. Caco-2 cell lines were used for transport studies with RTV coarse powder, physical mixtures and nanosuspension. Results: Approximately 600 nm PS, 0.4 PDI and 22 mV ZP values were observed for nanosuspensions. The sample groups showed no cytotoxicity on the cell lines in any RTV concentration. However, significant cytotoxic effect was determined in groups with high amounts of sodium dodecyl sulfate. The transported RN in nanosuspension formulation enhanced by 5.3-fold and 1.5-fold in comparison with RTV coarse powder and physical mixture, respectively. Rate of the transportation and also the amount of the transported RTV were improved with nanosuspension formulation. Conclusion: Particle size reduction of RTV into nanometer size and preparing nanosuspension system was found effective to obtain enhanced cell permeability.