Antibody Conjugated Nano-Enabled Drug Delivery Systems Against Brain Tumors.

The use of antibody-conjugated nanoparticles for brain tumor treatment has gained significant attention in recent years. Nanoparticles functionalized with anti-transferrin receptor antibodies have shown promising results in facilitating nanoparticle uptake by endothelial cells of brain capillaries and post-capillary venules. This approach offers a potential alternative to the direct conjugation of biologics to antibodies. Furthermore, studies have demonstrated the potential of antibody-conjugated nanoparticles in targeting brain tumors, as evidenced by the specific binding of these nanoparticles to brain cancer cells. Additionally, the development of targeted nanoparticles designed to transcytoses the blood-brain barrier (BBB) to deliver small molecule drugs and therapeutic antibodies to brain metastases holds promise for brain tumor treatment. While the use of nanoparticles as a delivery method for brain cancer treatment has faced challenges, including the successful delivery of nanoparticles to malignant brain tumors due to the presence of the BBB and infiltrating cancer cells in the normal brain, recent advancements in nanoparticle-mediated drug delivery systems have shown potential for enhancing the efficacy of brain cancer therapy. Moreover, the development of brain-penetrating nanoparticles capable of distributing over clinically relevant volumes when administered via convection-enhanced delivery presents a promising strategy for improving drug delivery to brain tumors. In conclusion, the use of antibody-conjugated nanoparticles for brain tumor treatment shows great promise in overcoming the challenges associated with drug delivery to the brain. By leveraging the specific targeting capabilities of these nanoparticles, researchers are making significant strides in developing effective and targeted therapies for brain tumors.

A Randomized Comparison Between Interscalene and Combined Interscalene-Suprascapular Blocks for Arthroscopic Shoulder Surgery: A Prospective Clinical Study.

Background: To compare the analgesic effect of ISB with a combination of ISB-SSNB and patients who were given opioids with PCA without block in adult patients undergoing shoulder surgery, as measured by opioid consumption and pain intensity in the first 24 hours postoperatively. Methods: Ninety patients who underwent shoulder surgery were randomly divided into three groups. Group I in which ISB was performed and patient-controlled analgesia (PCA) was inserted, Group II with; ISB and SSNB combined, and PCA was inserted, and Group III where; only PCA was used. Visual analog scale (VAS) pain scores at the second, fourth, sixth, 12th, and 24th hours, morphine consumption, additional analgesic requirement, and patient satisfaction were evaluated. Results: Compared with Group III, the VAS pain score was significantly lower in Group I and Group II at 2, 4, 6, 12, and 24 hours postoperatively. In Group I, the VAS score at rest at the 6th hour was found to be higher than in Group II. The 24-hour total morphine consumption was higher in the control group than in Group I and Group II. The satisfaction score of the control group was lower than Group I and Group II. Conclusion: The combined application of ISB and SSNB block is beneficial in shoulder surgery to provide both intraoperative and postoperative analgesia and opioid consumption. Level of Evidence: Level I; Randomized Controlled Trial; Treatment Study.

The effect of playing music and mother's voice to children on sedation level and requirement during pediatric magnetic resonance imaging.

BACKGROUND: Magnetic resonance imaging examinations frequently cause anxiety and fear in children. The objective of this study was to investigate the effects of listening to music sound, the mother's voice, and sound isolation on the depth of sedation and need for sedatives in pediatric patients who would undergo MRI. METHODS: Ninety pediatric patients aged 3 to 12 years who were planned for imaging in the MRI unit were randomly assigned to isolation group (Group I), musical sound group (Group II), and mother's voice group (Group III). We evaluated patients' anxiety and sedation levels via the Observer's Assessment of Alertness/Sedation (OAA/S) RESULTS: Heart rate, oxygen saturation, OAA/S, and Ramsey scores during the procedure were not significantly different among the groups (p>0.05). The mean amount of propofol and total propofol consumption was statistically lower in the mother's voice group than in the isolation and music sound groups (p<0.001). Mean propofol amount and total propofol consumption were not significantly different in isolation and music sound groups (p>0.05). No difference was found between the groups regarding the time it took for the patients' Modified Aldrete score to reach 9 (p>0.05). CONCLUSIONS: In pediatric patients, listening to the mother's voice during MRI decreased the total sedative requirement consumed without increasing the depth of sedation.

The neuroprotective effect of mesenchymal stem cells in colistin-induced neurotoxicity.

Colistin is an effective antibiotic against multidrug-resistant gram-negative bacterial infections; however, neurotoxic effects are fundamental dose-limiting factors for this treatment. Stem cell therapy is a promising method for treating neuronal diseases. Multipotent mesenchymal stromal cells (MSC) represent a promising source for regenerative medicine. Identification of neuroprotective agents that can be co-administered with colistin has the potential to allow the clinical application of this essential drug. This study was conducted to assess the potential protective effects of MSC, against colistin-induced neurotoxicity, and the possible mechanisms underlying any effect. Forty adult female albino rats were randomly classified into four equal groups; the control group, the MSC-treated group (A single dose of 1 × 106/mL MSCs through the tail vein), the colistin-treated group (36 mg/kg/d colistin was given for 7 d) and the colistin and MSC treated group (36 mg/kg/d colistin was administered for 7 d, and 1 × 106/mL MSCs). Colistin administration significantly increased GFAP, NGF, Beclin-1, IL-6, and TNF-α immunreactivity intensity. MSC administration in colistin-treated rats partially restored each of these markers. Histopathological changes in brain tissues were also alleviated by MSC co-treatment. Our study reveals a critical role of inflammation, autophagy, and apoptosis in colistin-induced neurotoxicity and showed that they were markedly ameliorated by MSC co-administration. Therefore, MSC could represent a promising agent for prevention of colistin-induced neurotoxicity.

Clinical efficacy of ultrasound guided erector spinae plane block in patients undergoing microwave ablation.

OBJECTIVES: To compare the effect of pre-emptive erector spinae plane block (ESPB) applied before the procedure on opioid consumption during the procedure and analgesic demand and opioid consumption after the procedure. METHODS: American Society of Anesthesiologists Physical Status Classification (ASA) I-II, 30 patients, with liver tumor and planned for microwave ablation (MWA) treatment were included in the interventional radiology clinic, Erciyes University, Kayseri, Turkey, Turkey between 2021 and 2022. Patients were randomized either to the ESPB or control group. Ultrasound-guided ESPB block with 20 mL of 0.25% bupivacaine was performed preoperatively in the ESPB group patients, and the patients who was not performed the ESPB the control group. All the patients were administered 1 µg/kg fentanyl, 1-2 mg/kg propofol, and 1 mg/kg ketamine for sedation during the MWA procedure after standard monitoring. Total opioid consumption and numeric rating scale (NRS) scores for pain were recorded at 0, 20, 40, and 60 minutes, and at 2, 4, 6, 12, and 24 hours after the procedure. RESULTS: Total opioid consumption and total opioid amount during the procedure were statistically significantly lower in the ESPB group (p<0.001). Although all of the patients in the control group needed additional fentanyl throughout the procedure, only 5 patients in the ESPB group needed additional fentanyl (p<0.001). Post-procedure NRS score values were significantly lower in the ESPB group at 40 minutes, 60 minutes and 4 hours (p<0.05). Numeric rating scale values at other times were statistically similar (p>0.05) CONCLUSION: This study showed that ESPB provided effective preemptive analgesia during MWA procedures.

Efficacy of stem cell-based therapies for colistin-induced nephrotoxicity.

The increase in infections with multidrug resistant bacteria has forced to return to the use of colistin, antibiotic with known nephrotoxicity. Mesenchymal stem cells (MSCs) are being extensively investigated for their potential in regenerative medicine. This study aimed to investigate the possible protective mechanisms of the MSCs against kidney injury induced by colistin. Forty adult female albino rats were randomly classified into 4 equal groups; the control group, the MSC-treated group (a single dose of 1 ×106 /ml MSCs through the tail vein), the colistin-treated group (36 mg/kg/day colistin was given for 7 days), and the both colistin and MSC group (36 mg/kg/day colistin and 1 ×106 /ml MSCs). Main outcome measures were histopathological alterations, kidney malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and immunohistological autophagy evaluation. MSC repressed the progression of colistin-induced kidney injury as evidenced by the improvement of histopathological alterations and the substantial increase MDA, and decrease SOD and CAT in serum levels. Moreover, MSC resulted in a profound reduction in oxidative stress as manifested by decreased MDA and increased SOD in serum. Notably, MSC suppressed colistin-induced autophagy; it reduced renal levels of Beclin-1, P62 and LC3A/B. Furthermore, MSC decreased renal levels of eNOS. Lastly, MSC efficiently decreased expression of the TUNEL positive cell number. MSC confers protection against colistin-induced kidney injury by alleviating oxidative stress, nitric oxide synthase besides modulating reducing autophagy and apoptosis.

Design of Besifloxacin HCl-Loaded Nanostructured Lipid Carriers: In Vitro and Ex Vivo Evaluation.

Objective: In the treatment of severe cases of bacterial keratitis, conventional eye drops containing antibiotics should be applied daily and very frequently. The aim of this study is to develop low-dose high-effect formulations with the prepared nanostructured lipid carrier (NLC) formulations to reduce antibiotic resistance and increase patient compliance. Methods: NLC formulations were loaded with besifloxacin HCl (BHL) and the besifloxacin HCl: sulfobutyl ether beta-cyclodextrin (SBE-CD) complex. Positive charge was gained with chitosan, and corneal permeation and resolubility were increased with SBE-CD. In vitro characterization studies, permeability studies, and cytotoxicity and ex vivo transport studies were carried out. Results: In this study, it was found that SBE-CD increased BHL's solubility by 8-fold based on phase solubility studies. The optimized NLCs were small in size (13.63-16.09 nm) with a low polydispersity index (0.107-0.181) and adequate BHL drug loading efficiency. In vitro release studies showed that formulations were released approximately for 8 h and at levels over the minimum inhibitory concentration of Pseudomonas aeruginosa and Staphylococcus aureus. NLC formulations had a better corneal permeation rate than the marketed product during 6 h of ex vivo studies. Conclusions: According to in vitro and ex vivo data, it was determined that the most favorable NLC formulation was the formulation containing BHL/SBE-CD that was covered with chitosan. It has the highest drug loading capacity and one of the highest ex vivo corneal passage levels, along with desired drug release. The formulation containing BHL/SBE-CD and chitosan can be a potential alternative for the treatment of bacterial keratitis.

Novel Drug Delivery Systems to Improve the Treatment of Keratitis.

Keratitis is a disease characterized by inflammation of the cornea caused by different pathogens. It can cause serious visual morbidity if not treated quickly. Depending on the pathogen causing keratitis, eye drops containing antibacterial, antifungal, or antiviral agents such as besiloxacin, moxifloxacin, ofloxacin, voriconazol, econazole, fluconazole, and acyclovir are used, and these drops need to be applied frequently due to their low bioavailability. Studies are carried out on formulations with extended residence time in the cornea and increased permeability. These formulations include various new drug delivery systems such as inserts, nanoparticles, liposomes, niosomes, cubosomes, microemulsions, in situ gels, contact lenses, nanostructured lipid carriers, carbon quantum dots, and microneedles. Ex vivo and in vivo studies with these formulations have shown that the residence time of the active substances in the cornea is prolonged, and their ocular bioavailability is increased. In addition, in vivo studies have shown that these formulations successfully treat keratitis. However, it has been observed that fluoroquinolones are used in most of the studies; similar drug delivery systems are generally preferred for antifungal drugs, and studies for viral and acanthameba keratitis are limited. There is a need for new studies on different types of keratitis and different drug active substances. At the same time, proving the efficacy of drug delivery systems, which give promising results in in vivo animal models, with clinical studies is of great importance for progress in the treatment of keratitis.

The effect of passive smoking on the laryngospasm rate in children sedated during the esophagogastroduodenoscopy.

OBJECTIVES: To investigate the rate of laryngospasm with sedation during the esophagogastroduodenoscopy (EGD) procedure in children exposed to passive smoking and to examine the frequency of complications due to laryngospasm. METHODS: A single-blind, prospective, observational study with a total of 518 patients evaluated according to the American Society of Anesthesiologists (ASA) physical status as classification I-II, aged between 1-18 years, and planned to undergo an EGD procedure, were included. Age, gender, weight, ASA assessment, exposure to smoking (the mother, the father, both parents were smokers, or not exposed to smoking), drug doses used in sedation, and anesthesia-related complications, such as cough, decrease in oxygen saturation, and laryngospasm were recorded. RESULTS: Of the 518 patients included in the study, 213 had no smoking exposure history. Oxygen saturation did not decrease below 90% in patients who did not have any smoking exposure. In addition, no laryngospasm was observed in this group. However, 4 (11.4%) of 31 patients whose mother only smoked, 10 (5.1%) of 187 child patients whose father only smoked, and 12 (16.4%) of 61 patients whose mother and father both smoked experienced laryngospasm during the procedure. CONCLUSION: The rate of cough, laryngospasm, and hypoxia development increased during the sedation carried out in the EGD procedure in children who were exposed to passive smoke.Clinicaltrial.gov ID: NCT03920046.

Confocal reflectance microscopy for metal and lipid nanoparticle visualization in the brain.

Aim: A requirement for nanoparticle (NP) research is visualization of particles within cells and tissues. Limitations of electron microscopy and low yields of NP fluorescent tagging warrant the identification of alternative imaging techniques. Method: Confocal reflectance microscopy (CRM) in combination with fluorescence imaging was assessed for visualizing rhodamine B-conjugated silver and fluorescein isothiocyanate-conjugated lipid core-stearylamine NP uptake in vitro and in vivo. Results: CRM successfully identified cellular uptake and blood-brain barrier penetration of NPs owing to their distinguishing refractive indices. NP-dependent reflectance signals in vitro were dose and incubation time dependent. Finally, CRM facilitated the distinction between nonspecific fluorescence signals and NPs. Conclusion: These findings demonstrate the value of CRM for NP visualization in tissues, which can be performed with a standard confocal microscope.

Nanoparticles (NPs) are extremely small materials utilized in the healthcare sector mainly for the delivery of drugs into tissues that are not easily accessible with regular pharmaceuticals. One such tissue is the brain, which has a barrier between it and the bloodstream that prevents the passage of most drugs. For NP research, the successful entry of NPs into target tissues must be demonstrated, but this is complicated by the small size and weak labeling of NPs. In this article, the authors demonstrate a low-cost, complementary microscopy technique that is readily available in most biological research laboratories and that can be used to detect and analyze the entry of different NP types into brain tissue and their uptake by brain tumor cells. These data create new opportunities for research on NP-assisted drug delivery to the central nervous system.

Fluoroscopy-guided balloon dilatation of benign esophageal strictures in children: 11-year experience.

BACKGROUND: The esophageal stricture is an important clinical problem in children, and the treatment is difficult. OBJECTIVE: To evaluate the results of fluoroscopy-guided balloon dilatation of benign pediatric esophageal strictures and to suggest a safety range for balloon diameters. MATERIALS AND METHODS: We retrospectively reviewed the medical records of children who underwent fluoroscopy-guided esophageal balloon dilatation for treatment of benign esophageal stricture from February 2008 to July 2019. We recorded the demographic data of the children, technical details of each procedure, balloon diameter, number of repeated procedures, clinical and technical success rates, complications and follow-up period. Technical success was defined as the disappearance of the waist formation on the balloon catheter, and clinical success was defined as no need for re-dilation or other treatment methods during the 1-year follow-up after the procedure. These children were divided into groups and evaluated according to esophageal stricture etiology. RESULTS: Technically successful procedures included 375 balloon dilatations in 116 patients (67 boys; age range: 1 month to 18 years; mean age: 4.3 ± 4.8 standard deviation [SD] years at the initial dilatation). The follow-up period was 1-138 months (median: 41 months; mean: 44 months) since the last dilatation. In this study, the clinical success rate was 34% per procedure (120 of 353 procedures) and 85% per patients (91 of 107 patients). The total complication rate per procedure was 0.5%, and the perforation rate was 0.25% per session. CONCLUSION: Fluoroscopy-guided esophageal balloon dilatation is an effective and reliable method for treating benign esophageal strictures in children.

Effect of mesenchymal stem cells therapy in experimental kaolin induced syringomyelia model.

BACKGROUND: Syringomyelia is a pathological cavitation of the spinal cord. In this study, we examined whether a syrinx cavity would limit itself with axonal regeneration and stem cell activity in the cavity, and we evaluated subjects on a functional basis. METHODS: Groups were designated as kaolin, trauma, kaolin-trauma, and saline groups. Also divided out of the syringomyelia treated groups were those given human mesenchymal stem cells (hMSCs). All groups were evaluated with immunohistochemistry, electron microscopy, confocal microscopy and functionally. RESULTS: The kaolin-trauma group had a significant correction of BBB score with hMSCs therapy. The syrinx cavity measurements showed significant improvement in groups treated with hMSCs. The tissue surrounding the syrinx cavity, however, appeared to be better organized in groups treated with hMSCs. The process of repair and regeneration of damaged axons in the lesion were more improved in groups treated with hMSCs. Using confocal microscopy, fluorescence of hMSCs was observed in the central canal, in the ependymal tissue, and around the lesion. CONCLUSIONS: It was concluded that axonal repair accelerated in groups receiving stem cells, and thus, stem cells may be effective in recovery of neural tissue and myelin damage in syringomyelia.

Investigation of the effects of propofol/ketamine versus propofol/fentanyl on nausea- vomiting administered for sedation in children undergoing magnetic resonance imaging: a prospective randomized double-blinded study

Background/aim: In this study, we aimed to compare the effects of propofol-ketamine and propofol-fentanyl sedations on post- procedure nausea-vomiting in children undergoing magnetic resonance imaging (MRI). Materials and methods: This study included 100 pediatric patients (2­10 years old) who had propofol-ketamine and propofol-fentanyl for sedation to undergo MRI. The patients were divided into two groups, and sedation was performed through propofol-ketamine (Group K; n = 50) or propofol-fentanyl (Group F; n = 50). For sedation induction, intravenous (IV) bolus of 1.2 mg/kg propofol and 1 mg/kg ketamine were administered in Group K, IV bolus of 1.2 mg/kg propofol, and 1 µg/kg fentanyl in Group F. All patients received 0.5 mg/kg IV bolus propofol in additional doses when the Ramsay Sedation Score (RSS) was below 4 for maintenance. Perioperative heart rate, systolic arterial pressure, peripheral oxygen saturation, respiratory rate, and nausea-vomiting scores were recorded for each patient. Results: There was no difference between the groups in terms of nausea incidences at the 1st hour. However, the rate of vomiting was significantly higher in Group K. Conclusion: In our study, we showed that the vomiting rate was higher in the 1st hour in Group K compared to Group F.

Postoperative Thoracic Pain Treatment: Serratus Anterior or Erector Spinae Plane Block?

BACKGROUND: Thoracic surgery is one of the most painful surgeries. Effective analgesia is important in postoperative pain management. In this study, we aimed to compare the two new fascial block techniques. METHODS: A total of 107 patients who underwent thoracic surgery between October 2018 and November 2019 were retrospectively evaluated. The study included 59 patients in the serratus anterior plane block (SAPB) group and 48 patients in the erector spinae plane block (ESPB) group. Both groups were administered 30 mL of 0.25% bupivacaine and their morphine consumption was evaluated by a patient-controlled analgesia (PCA) method during the 2nd, 6th, 12th, 24th, and 48th postoperative hours. Pain was measured with the visual analog scale (VAS). Intraoperative mean arterial pressure (MAP) and heart rate (HR) were recorded. RESULTS: During the first 24 hours, VAS values were significantly lower in the ESPB group (p < 0.05). Moreover, morphine consumption was significantly lower in the ESPB group in the 24th and 48th hours (p < 0.05). Intraoperative remifentanil consumption was also significantly lower in the ESPB group (p < 0.05). Intraoperative MAP in the ESPB group was found to be significantly lower after the 4th hour. HR was similar in both groups. CONCLUSION: ESPB was more effective compared with SAPB in postoperative thoracic pain management.

Development of besifloxacin HCl loaded nanofibrous ocular inserts for the treatment of bacterial keratitis: In vitro, ex vivo and in vivo evaluation.

Novel drug delivery systems have emerged to treat bacterial keratitis, an acute infection of the cornea. In this study, besifloxacin HCl loaded insert formulations were designed and investigated in vitro, ex vivo and in vivo for the treatment of bacterial keratitis. Besifloxacin HCl (BH) or BH-hydroxypropyl-beta-cyclodextrin (HP-ß-CD) complex containing poly(caprolactone)/polyethylene glycol (PLC/PEG) fibrous inserts were prepared with an electrospinning method. These fibrous inserts were coated with mucoadhesive polymers such as sodium alginate (SA) or thiolated sodium alginate (TSA). Developed inserts compared to commercially available drug and it was found that coating of the insert surfaces with SA and TSA, increases bioadhesion of the formulations. Insert formulations showed a burst release in the first 2 days followed by a slow-release profile. Ex vivo transport studies showed that HP-ß-CD possessed a drug delivery level close to the commercial drug. Both TSA coated inserts as well as inserts containing HP-ß-CD-drug complex were effectively reducing bacterial keratitis in rabbit eyes upon single-dose application compared to multiple dosing with the commercial drug. Consequently, TSA coated inserts as well as the inserts containing HP-ß-CD-drug complex, may be potential alternatives to conventional market product by reducing the application frequency in the clinic leading to increased patient compliance.

Design of ocular drug delivery platforms and in vitro - in vivo evaluation of riboflavin to the cornea by non-interventional (epi-on) technique for keratoconus treatment.

AIM: Keratoconus is a common and progressive eye disease characterized by thinning and tapering of the cornea. This degenerative eye disease is currently treated in the clinic with an interventional technique ("epi-off") that can cause serious side effects as a result of the surgical procedure. The aim of this project is to design innovative formulations for the development of a riboflavin-containing medicinal product to develop a non-invasive ("epi-on") keratoconus treatment as an alternative to current treatment modalities. METHODS: Nanostructured lipid carriers (NLCs) were successfully loaded with either riboflavin base of riboflavin-5-phosphate sodium and designed with either Stearylamine (positive charge) or Trancutol P (permeation enhancer). In vitro characterization studies, cytotoxicity and permeability studies were performed. Selected formulations and commercial preparations were applied and compared in ex-vivo corneal drug accumulation and transition studies. Furthermore, in vivo studies were performed to assess drug accumulation in the rat cornea and the corneal stability after NLC treatment was investigated via a biomechanical study on isolated rabbit corneas. RESULTS: Both in vitro and ex-vivo as well as in vivo data showed that from the prepared NLC formulations, the most effective formulation was riboflavin-5-phosphate sodium containing NLC with Transcutol P as permeation enhancer. It possessed the highest drug loading content, low accumulation in the cornea but high permeability through the cornea as well as the highest functional performance in corneal crosslinking. CONCLUSION: Topical application of riboflavin-5-phosphate sodium loaded NLC systems designed with permeation enhancer Transcutol P may act as a potential alternative for non-invasive keratoconus treatments.

Effects of dexmedetomidine and esmolol on otoacoustic emissions during controlled hypotensive anesthesia: randomized clinical trial.

PURPOSE: The aim of this study was to investigate the ability of esmolol and dexmedetomidine to achieve controlled hypotension on cochlea by measuring otoacoustic emission and stapedius reflex. METHODS: In this prospective, double-blind pilot study, patients scheduled for elective tympanoplasty, rhinoplasty and endoscopic sinus surgery operation were randomly assigned to two groups, and received either dexmedetomidine (n=23) or esmolol (n=24) during surgery to maintain a mean arterial blood pressure between 55 and 65 mmHg. Distortion product otoacoustic emission tests (DPOAE) were performed 24 hours before and after the operation and during surgery (in the 20th and 40th minutes of the operation). RESULTS: In the intra-group comparison, a statistically significant decrease was present at t20 (2,000 and 4,000 Hz frequency band) and t40 (1,000 and 1,500 Hz) according to the baseline value in the dexmedetomidine group (n=23); in the esmolol group (n=24), a statistically significant decrease (relative to the baseline value) was also detected at t20 and t40 for the 1,000 Hz frequency band. No damage was found on stapes reflexes with the infusion of these drugs. CONCLUSIONS: Infusion of dexmedetomidine and esmolol decreased DPOAE levels during the operations, but DPOAE levels returned to normal in the postoperative period, and had no effect on stapes reflexes. Studies with larger groups of patients are needed to confirm these results in tympanoplasty and other surgeries.

Development of an Anti-Inflammatory Drug-Incorporated Biomimetic Scaffold for Corneal Tissue Engineering.

Purpose: The aim of this study was to design naproxen sodium (NS)-containing, biomimetic, porous poly(lactide-co-glycolide) (PLGA) scaffolds for regeneration of damaged corneal epithelium. Methods: NS-incorporated PLGA scaffolds were prepared using the emulsion freeze-drying method and then coated with collagen or poly-l-lysine. Porosity measurements of the scaffolds were performed by the gas adsorption/desorption method and the scaffolds demonstrated highly porous, open-cellular pore structures with pore sizes from 150 to 200 µm. Results: The drug loading efficiency of scaffolds was found to be higher than 84%, and about 90%-98% of NS was released at the end of 7 days with a fast drug release rate at the initial period of time and then in a slow and sustained manner. The corneal epithelial cells were isolated from New Zealand white rabbits. The obtained cells were seeded onto scaffolds and continued to increase during the time period of the study, indicating that the scaffolds might promote corneal epithelial cell proliferation without causing toxic effects for at least 10 days. Conclusions: The NS-loaded PLGA scaffolds exhibited a combination of controlled drug release and biomimetic properties that might be attractive for use in treatment of corneal damage both for controlled release and biomedical applications.

Development and evaluation of orally disintegrating tablets comprising taste-masked mirtazapine granules.

INTRODUCTION: Orally disintegrating tablets (ODTs) provide an important treatment option for pediatric, geriatric and psychiatric patients. In our previous study, we have performed the initial studies for the formulation development and characterization of new ODT formulations containing a bitter taste drug, mirtazapine, coated with 6% (w/w) Eudragit® E-100 (first group of formulations, FGF) without taste evaluation. In present study, coating ratio of the drug was increased to 8% (w/w) (second group of formulations, SGF) to examine the effect of increased coating ratio of drug on in vitro characterization of the formulations including in vitro taste masking study. MATERIALS AND METHODS: Coacervation technique using Eudragit® E-100 was employed to obtain taste-masked mirtazapine granules. FGF and SGF were compared to original product (Remeron SolTab, an antidepressant drug which produced by pellet technology) in terms of in vitro permeability, in vitro taste masking efficiency which was performed by dissolution studies in salivary medium and dissolution stability. Also, the other tablet characteristics (such as diameter, thickness) of SGF were examined. RESULTS AND DISCUSSION: The disintegration time of the SGF were found as A1 < A2 < A3 < A5 < A4 (8% Eudragit® E-100), but all of the formulations dissolved under 30 seconds and friability values were less than 1%. In vitro taste masking efficiency studies demonstrated that C2 formulation (in FGF) had the most similar dissolution profile to Remeron SolTab. CONCLUSIONS: According to these findings, B2 or C2 (with citric acid or sodium bicarbonate, respectively, with 6% Eudragit® E-100) formulations could be promising alternatives to Remeron SolTab.

A potential non-invasive glioblastoma treatment: Nose-to-brain delivery of farnesylthiosalicylic acid incorporated hybrid nanoparticles.

New drug delivery systems are highly needed in research and clinical area to effectively treat gliomas by reaching a high antineoplastic drug concentration at the target site without damaging healthy tissues. Intranasal (IN) administration, an alternative route for non-invasive drug delivery to the brain, bypasses the blood-brain-barrier (BBB) and eliminates systemic side effects. This study evaluated the antitumor efficacy of farnesylthiosalicylic acid (FTA) loaded (lipid-cationic) lipid-PEG-PLGA hybrid nanoparticles (HNPs) after IN application in rats. FTA loaded HNPs were prepared, characterized and evaluated for cytotoxicity. Rat glioma 2 (RG2) cells were implanted unilaterally into the right striatum of female Wistar rats. 10days later, glioma bearing rats received either no treatment, or 5 repeated doses of 500µM freshly prepared FTA loaded HNPs via IN or intravenous (IV) application. Pre-treatment and post-treatment tumor sizes were determined with MRI. After a treatment period of 5days, IN applied FTA loaded HNPs achieved a significant decrease of 55.7% in tumor area, equal to IV applied FTA loaded HNPs. Herewith, we showed the potential utility of IN application of FTA loaded HNPs as a non-invasive approach in glioblastoma treatment.