Facial nerve function and hearing after microsurgical removal of sporadic vestibular schwannomas in a population-based cohort.

BACKGROUND: Vestibular schwannoma (VS) is a benign tumor originating from the vestibulocochlear nerve. The optimal treatment strategy is debated, since surgery may result in iatrogenic facial nerve injury. We report the results of VS surgery in a population-based unselected cohort in a center with access to Cyber Knife (CK) radiosurgery. METHODS: We reviewed 117 consecutive operations and found 95 patients who had their primary operation due to vestibular schwannoma between 2001 and 2017. Facial nerve function was evaluated with the House-Brackmann (HB) scale and hearing with the EU classification. RESULTS: The population consisted of 37 males and 58 females with a median age of 54 years (range 19-79). One year after surgery 67% of patients had a good outcome (HB 1-2). The rate of good outcome was 90% if no facial nerve damage was observed during intraoperative monitoring, the size of the tumor was under 30 mm and no hydrocephalus was present. During the study period, the treatment strategy changed from total to near-total resection after the introduction of CK radiosurgery, which could be used as a second-line treatment in case of residual tumor regrowth. This resulted in an improvement of outcomes (0% HB 5-6) despite the larger tumor sizes (25 ± 14 mm vs. 31 ± 9 mm, p < 0.05). Hearing preservation rates did not increase. CONCLUSIONS: Near-total resection and subsequent CK radiosurgery in case of residual tumor regrowth during follow-up seems to provide a good outcome of facial nerve function even in large VSs.

Dosimetry and Biochemical Comparison of Early Radiation-Induced Lung Toxicity in Breast Cancer Patients Treated with 3D-CRT and IMRT: the Role of Serum Interleukin-6 and Pulmonary Surfactant Protein-D.

BACKGROUND: Radiation-induced lung disease is a potentially fatal, dose-limiting toxicity commonly seen after radiotherapy of thoracic malignancies, including breast cancer. AIM: To evaluate and compare the early lung toxicity induced by 3D-CRT and IMRT radiotherapy treatment modalities in breast cancer female patients using biochemical, dosimetry and clinical data. SUBJECTS AND METHODS: this study included 15 normal healthy controls, 15 breast cancer patients treated with IMRT, and 15 breast cancer patients treated with 3D-CRT. One blood sample was obtained from the control group and 3 blood samples were withdrawn from cases before RT, after RT and after 3 months of RT. RESULT: IMRT delivered higher radiation dose to the breast tumor and lower doses to the lung as an organ at risk. There was a non-significant increase in the serum levels of IL-6 before IMRT and 3D-CRT compared with its levels in the control group. There were significant increases in serum levels of IL-6 after RT (IMRT and 3DCRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of IL-6 after 3 months of RT (IMRT and 3D-CRT) compared with its serum levels immediately after RT. There was a non-significant increase in the serum levels of SP-D before RT (IMRT and 3D-CRT) compared with its levels in the control group. There were significant-increases in serum levels of SP-D after RT (IMRT and 3D-CRT) compared with its levels before RT. There was a non-significant decrease in the serum levels of SP-D after 3 months of radiotherapy (IMRT and 3D-CRT) compared with its serum levels immediately after RT. CONCLUSION: serum of levels IL-6 and SP-D can be used to diagnose the occurrence of early lung toxicity due to radiotherapy and the rate of recovery from radiation pneumonitis is apparent in case of IMRT than 3D-CRT.

Simultaneous pulmonary administration of celecoxib and naringin using a nebulization-friendly nanoemulsion: A device-targeted delivery for treatment of lung cancer.

BACKGROUND: Lung cancer is a principal cause of death worldwide, and its treatment is very challenging. Nebulization offers a promising means of targeting drugs to their site of action in the lung. RESEARCH DESIGN AND METHODS: In the present study, nebulizable oil in water nanoemulsion formulations was co-loaded with naringin/celecoxib and tested for pulmonary administration by different nebulizer types. RESULTS: The translucent appearance of nanoemulsion formulations was revealed, with particle size (75-106 nm), zeta potential (-3.42 to -4.86 mV), and controlled in-vitro release profiles for both drugs. The nanoemulsions showed favorable stability profiles and superior cytotoxicity on A549 lung cancer cells. Aerosolization studies on the selected nanoemulsion formulation revealed its high stability during nebulization, with the generation of an aerosol of small volume median diameter and mass median aerodynamic diameter lower than 5 µm. Moreover, it demonstrated considerable safety and bioaccumulation in lung tissues, in addition to accumulation in the brain, liver, and bones, which are the main organs to which lung cancer metastasizes. CONCLUSIONS: Nanoemulsion proved to be a promising nebulizable system, which paves the way for treatment of pulmonary diseases other than lung cancer.

A novel serum-stable liver targeted cytotoxic system using valerate-conjugated chitosan nanoparticles surface decorated with glycyrrhizin.

The aim of this study was to target a naturally chemotherapeutic agent: ferulic acid to the liver using a biocompatible and an in vivo stable carrier. Accordingly, chitosan as a biopolymer was modified using a hydrophobic moiety and valeric acid in order to increase its in vivo stability. The structure of the newly synthesized product was confirmed using FT-IR and NMR techniques together with the ninhydrin assay. Ferulic acid was conjugated to the modified nanoparticles that were further characterized for particle size, PDI and zeta potential and subjected to ex vivo stability study in serum and cytotoxicity studies in HepG2 cell lines. Furthermore, the nanoparticles were surface-decorated with glycyrrhizin for active liver targeting. The in vivo biodistribution was experimented using radiolabeling assay where the liver scored the highest accumulation of the glycyrrhizin containing nanoparticles after 6h reaching a value of 13.34%ID/g of the total injected dose of labeled drug compared to drug solution and glycyrrhizin free nanoparticles where the accumulation percent did not exceed 4.19%ID/g and 4.26%ID/g, respectively. As a conclusion, the conducted physico-chemical and biological investigations suggested that the proposed selected system can be efficiently utilized as a successful platform for targeting a natural chemotherapeutic agent viz. ferulic acid to the liver.

Nebulizable colloidal nanoparticles co-encapsulating a COX-2 inhibitor and a herbal compound for treatment of lung cancer.

A challenging disease such as lung cancer requires the combination of different modalities to achieve beneficial therapeutic outcomes. In this work, PLGA nanoparticles were chosen as colloidal carrier for two drugs with reported anti-lung cancer activity: naringin and celecoxib. PLGA nanoparticles were prepared and characterized for their particle size, zeta potential, entrapment efficiency, in vitro release, stability, morphology, cytotoxicity, as well as aerosolization and nebulization behaviors. Their biodistribution pattern upon pulmonary aerosolization, and safety on healthy lung tissues were determined as well. Results showed that the described system displayed a particle size <260nm with unimodal distribution, entrapment efficiency for celecoxib and naringin reaching 96% and 62% respectively and a controlled release profile for the two drugs. The selected formula displayed favorable nebulization properties with high drug deposition percentages in lower impinger and impactor stages. It also exhibited higher cytotoxic activity on A549 lung cancer cell lines compared to the free drugs combination, while displaying considerable safety on healthy lung tissues. Biodistribution studies delineated the lung deposition potential of the nanoparticles accompanied with high distribution to the bones, brain and liver which are common metastatic sites of lung cancer, proving their promising nature in the treatment of lung cancer.

Suitability of liposomal carriers for systemic delivery of risedronate using the pulmonary route.

OBJECTIVE: This study aims at testing the hypothesis that reversed phase evaporation liposomes (REVs) are suitable for systemic delivery of an anti-osteporotic drug (risedronate sodium (RS)) via pulmonary nebulization. MATERIALS AND METHODS: RS REVs were prepared using phospholipids and cholesterol with or without stearylamine, and were characterized for morphology, entrapment efficiency (EE%), in vitro release, particle size and aerosolization behavior from an actively vibrating mesh nebulizer. RS accumulation in rat bones following intra-tracheal administration of the selected formulation was assessed using a radiolabelling-based technique, and histological examination of rat lung tissue was performed to assess its safety. RESULTS: The EE% of RS REVs ranged from 8.8% to 58.96% depending on cholesterol molar ratio, phospholipid type and presence of stearylamine. RS REVs' particle size ranged from 2.15 to 3.61 µm and were spherical and moderately polydisperse. Nebulization of the selected formulation showed an aerosol output of 85%, a fine particle fraction of 70.75% and a predicted alveolar deposition of 30.39%. The amount of radiolabelled RS deposited in rat bones after pulmonary administration was 20%, while being considerably safe on lung tissues. CONCLUSION: Cationic REVs is a promising carrier for systemic delivery of RS for treatment of bone resorptive diseases.

Different modalities of NaCl osmogen in biodegradable microspheres for bone deposition of risedronate sodium by alveolar targeting.

Risedronate sodium was formulated into polylactide-co-glycolic acid microspheres for pulmonary delivery using the w/o/w double emulsion technique. Sodium chloride was used as osmogen in either the internal or external aqueous phase to surface-engineer the particles to achieve favorable properties. The prepared microspheres were characterized for the surface morphology, entrapment efficiency, in vitro release behavior, particle size, surface area, aerodynamic as well as powder flow properties. Furthermore, the safety of the drug and the selected formula were assessed by MTT viability test performed on Calu-3 cell line as well as histopathological lung tissue examination. A novel in vivo approach based on the radiolabeling of risedronate sodium with I(125) was developed in order to assess its deposition in the bones of male albino rats. The majority of the prepared microspheres exhibited high entrapment efficiency, sustained release profile up to 15 days, suitable geometric and aerodynamic particle sizes as well as good flow properties. The safety of the drug and the selected formula were proven by the high cell viability percentage of Calu-3 cells as well as the normal lung histology after intra-tracheal administration. The in vivo study showed high bone deposition for risedronate sodium following the pulmonary route, suggesting that it could be utilized as an alternative route of administration for delivery of bisphosphonates.