Ebru Başaran

Introduction/Objective: Letrozole (LTZ)-loaded polymeric nanoparticles (PNPs) were formulated with Eudragit® RS100 to investigate their potential as a preliminary drug delivery system for hepatocellular carcinoma (HCC). Methods: Nanoparticles were prepared using the spray-drying technique with a Büchi B-90 Nano Spray Dryer and characterized in terms of morphology, particle size, polydispersity index (PDI), zeta potential, drug loading efficiency, thermal and structural characteristics, in vitro release behavior, and preliminary cytotoxicity. Results: SEM analysis demonstrated the formation of predominantly spherical particles with relatively smooth surfaces. The prepared nanoparticles exhibited initial particle sizes ranging between 253 nm and 425 nm, with PDI values of 0.3–0.4 and positive zeta potential values between 36 and 48 mV. Encapsulation efficiency (EE%) and drug loading (DL%) values were determined as 47.9%–56.9% and 9.1%–18.6%, respectively. Thermal and structural analyses indicated the molecular dispersion of LTZ within the polymeric matrix. In vitro release studies conducted at pH 7.4 demonstrated an initial burst release, followed by a sustained drug release profile over 24 h, with cumulative drug release reaching almost 80%. The preliminary cytotoxicity of the formulations was evaluated using the methylthiazolyl-diphenyl-tetrazolium bromide (MTT) assay on human hepatocellular carcinoma (HepG2) and healthy human dermal fibroblast (BJ) cell lines. Free LTZ demonstrated an IC50 value of 142.76 µg/mL against HepG2 cells, whereas the optimized nanoparticle formulation exhibited an IC50 value higher than 121.85 µg/mL Discussion: The obtained results confirmed the successful development of LTZ-loaded polymeric nanoparticles with suitable physicochemical properties, efficient drug encapsulation, and sustained release behavior. The positive surface charge and nanoscale size may support formulation stability. Furthermore, the nanoparticles preserved the cytotoxic activity of LTZ, indicating their potential as an effective drug delivery system. Conclusion: Overall, the findings suggest that the developed nanoparticles constitute a promising drug delivery system for further investigation in HCC-related therapy. However, additional mechanistic studies and in vivo evaluations are required to comprehensively assess their true therapeutic potential.

Objective: This study aims to formulate in-situ gel formulations for extended duration of indomethacin (INDO) on the corneal surface which will improve the ocular bioavailability for sufficial treatment of ocular inflammatory disorders. Material and Method: Formulations were prepared by cold method. Briefly polymers were dissolved in cold ultrapure water and INDO was added to the solutions. A modified UV method was used. DSC, FT-IR and 1H-NMR analyses were used for the determination of structural properties of INDO and excipients. The formulations were characterized through measurements of gelation temperature and gelation time, determination of pH, rheological assessments, and in vitro drug release experiments conducted in PBS (pH 7.4) at 34 ± 2°C. Result and Discussion: According to the gelation temperature and gelation time analyses optimum formulation which contained %17 (w/w) Poloxamer 407 (P407) was selected for further studies. Evidence of drug–polymer compatibility was obtained through DSC, FT-IR, and ¹H-NMR studies. INDO was loaded to the formulation at 0.1% (w/w). pH of the formulation was 5.29±0.00 and considering the ocular tolerability no adjustment was required. The rheological analyses revealed the gel transition point at 34°C±2°C. In vitro release analyses revealed that even after 6 hours only 30% of the INDO was released from the formulations showing the extended release of the active agent with the help of transition of the eye drops to the solidified gel structure. These results support the notion that ocular bioavailability will be enhanced with P407 based in-situ gels considering extended retention time of INDO on the corneal surface.

Background: Chemotherapy is regarded as first-line therapy in various cancer types besides surgical procedures. However, lack of cell selectivity and poor drug targeting to the cancer zone of the active agents results in accumulation in normal tissues with considerably high severe side effects. Therefore, novel drug delivery systems are required to enhance cancer treatment. Objective: In this study, Paclitaxel (PTX) incorporated Kollidon® SR (KSR) and Chitosan (CS) based polymeric nanoparticles were prepared for potential use for colorectal cancer treatment. Methods: Polymeric nanoparticles were prepared by spray dying method. Physicochemical characterization studies were performed with particle size (PS), polydispersity index (PDI), zeta potential (ZP), drug loading (DL %), encapsulation efficiency (EE %) and structural evaluations using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR) analyses. Cytotoxicity of the nanoparticles was screened on HT-29 (human colorectal adenocarcinoma) and HTC-15 (Dukes' type C, colorectal adenocarcinoma) cell lines with MTT assay. Results: Analysis revealed the successful incorporation of PTX into the polymeric lattices. Particles showed cytotoxic activity on HT-29 and HTC-15 cell lines, depending on the application dose after 48 hours. Nanoparticles also remained stable at 5°C ± 3°C and 25°C ± 2°C (60% ± 5 Relative Humidity (RH)) during the storage period of 6 months. Conclusion: As a result of the study, KSR and CS-based nanoparticles could be regarded as promising nano-carriers for improved therapeutic efficacy of PTX for colorectal cancer treatment.

Background: The oral route is the primary route for both acute and chronic treatment of epilepsy. However, lack of oral access during the seizures and high drug resistance limit the antiepileptogenic effects of most antiepileptic drugs. Therefore, alternative routes and novel drug delivery systems are required. In this study, polymeric microneedles were formulated and characterized for possible intranasal administration of Tiagabine (TIA) in order to overcome the blood-brain barrier (BBB). Methods: In our study, carboxymethyl cellulose (CMC) and Eudragit® S 100 (ES100) based polymeric microneedles were formulated by micromolding method. Scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffractometry (XRD), fourier transform infrared spectroscopy (FT-IR) and proton nuclear magnetic resonance (1H-NMR), in vitro release, and texture analyses were performed. For the stability analyses, formulations were kept at 25°C ± 2°C (60 ± 5% Relative Humidity; RH), 40°C ± 2°C (75 ± 5% RH) and 5°C ± 3°C for six months. Results: Analysis results revealed that robust microneedles were formulated successfully by micromolding method with adjustable needle lengths. Depending on the polymer type, sustained TIA releases up to 72 hours were achieved. Structural integrities were maintained at all storage conditions during the storage period of six months. Conclusion: TIA-loaded microneedles have the potential with less invasive properties, even with small amounts of TIA, through the unconventional nasal route for effective treatment of epilepsy.

In our study Voriconazole (VOR) was selected as an active agent to be used for the treatment of ocular fungal infections. To overcome low aqueous solubility of VOR, inclusion complexes with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD), hydroxypropyl-cyclodextrin (HP-CD), hydroxypropyl-β-cyclodextrin (HP-β-CD) hydroxypropyl-γ-cyclodextrin (HP-γ-CD), methyl-β-cyclodextrin (M-β-CD) and sulfabutylether-β-cyclodextrin (SBE-β-CD) were formulated. Characterization studies revealed that inclusion complexes were formulated successfully with lyophilization method. Aqueous solubility of VOR was enhanced up to 86 fold with the formation of the inclusion complexes. MTT analyses results revealed the safety of the complexes on 3T3 mouse fibroblast cell lines while Microbroth Dilution Method revealed the remarkable antifungal activities of the complexes. Analyses results revealed that inclusion complexes will overcome the poor ocular bioavailability of VOR resulting in efficient treatment of severe ocular fungal infections.

Despite being the most effective hypolipidemic agent, poor physicochemical properties of Rosuvastatin calcium (RCa) remain challenging obstacles in development of pharmaceutical dosage forms. Inclusion complexes (ICs) of RCa with cyclodextrin (CD) derivatives; methyl-beta-cyclodextrin (M-β-CD) and sulfobutylether-beta-cyclodextrin (SBE-β-CD; Captisol^®) were formulated by kneading and freeze-drying (lyophilization) methods. Pysicochemical properties of ICs were evaluated by SEM, DSC, XRD, FT-IR, ¹H-NMR analyses. Entrapment efficiency (EE), water solubility, in vitro release analyses were also performed. Safety and efficacy of the ICs were analyzed by cytotoxicity and permeation studies on Caco-2 cell lines. Both CDs indicated A_L type phase solubility diagrams showing that [1:1] molar ratio. Apparent stability constants (K_1:1) were found to be 60.93 M⁻¹ for M-β-CD and 158.07 M⁻¹ for Captisol^®. High EE in the range of 93.50% to 105.40% were achieved. Molar solubility of RCa was increased 3.7 and 4.1 fold with M-β-CD and Captisol^® ICs respectively. In vitro release analyses have indicated the equivalence of dissolution profiles for M-β-CD and Captisol^® based ICs to that of pure RCa (f₂ > 50). Cytotoxicity studies on Caco-2 cell lines have revealed the safety of ICs for oral use. Permeability studies demonstrated that selected lyophilized F6 formulation have shown the best permeation rate with P_app value of 3.08x10⁻⁷ cm.sec⁻¹. Considering greater water solubility, lower toxicity, high efficiency of complexation as well as, RCa-like permeability and in vitro release behavior at pH 6.8; Captisol^® based lyophilized F6 formulation was selected as the best IC to be used in oral dosage forms of RCa.

Ocular drug delivery is a difficult challenge especially with topical intillation which results in rapid drainage and non-productive drug absorption. For the improvement of the pre-corneal retention time and enhancing the corneal permeability, colloidal drug delivery systems play an important role in enhancement of the ocular bioavailability. In this study, dirithromycin incorporated Kollidon^® SR-based polymeric nanoparticles, an antibacterial agent, were formulated for the efficient treatment of severe ocular bacterial infections. In this study, dirithromycin was incorporated into the Kollidon^® SR-based nanoparticles by spray drying method. In vitro characteristic properties were evaluated in detail during the storage period of three months at three different conditions. The results of in vitro analyses revealed that characteristic properties of the particles were remained unchanged during the storage period of three months. Kollidon^® SR-based polymeric nanoparticles are good candidates for drug delivery systems in the treatment of severe ocular bacterial infections with dirithromycin.