Fabricating Polymer/Surfactant/Cyclodextrin Hybrid Particles for Possible Nose-to-Brain Delivery of Ropinirole Hydrochloride: In Vitro and Ex Vivo Evaluation

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson’s disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson’s disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson’s disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing

Hydroxyapatite scaffolds produced from cuttlefish bone via hydrothermal transformation for application in tissue engineering and drug delivery systems

An increase in life expectancy due to improvements in healthcare, in parallel with high percentage of injures, because of traffic accidents and sport activities, has emerged as the primary reasons for the replacements of lost, infected, and damaged bones. Combined with tissue engineering, this is an area of great interest to regenerative medicine. Novel scaffolds development, providing a suitable environment that can favor osteoinduction for the newly formed bone is needed. Composite porous hydrogels, based on alginate and chitosan with the dispersed phase from powders of bioceramics, such as hydroxyapatite (HAp), are recently developed for this reason. This work presents a reverse and novel approach, where these two popular hydrogels are infiltrated in a 3D HAp-scaffold. More specifically, HAp is obtained from aragonite from cuttlefish bone via hydrothermal transformation. This reinforcement of HAp with alginate or chitosan hydrogels, through infiltration method gives to the final product proper mechanical potential for hard tissue regeneration. The structure of the produced scaffolds resembles the microstructure and the texture of the natural bone. These advanced scaffolds are easily handled by the surgeon while maintaining their porous structure during the implantation process to promote the regeneration of newly formed bone tissue. In particular, once such a scaffold is implanted in an area where the bone tissue is lost, biological liquids will be able to penetrate into the pores of the lyophilized composite scaffold. The polymeric matrix will then be dissolved and the remaining HAp, or its precursor compounds, which will eventually transform into HAp, will promote osteoinduction. The worldwide availability and the low cost of cuttlefish bone, along with their biological-natural origin are attractive features making them highly sorted material used in the preparation of advanced scaffolds containing HAp for applications in biomedicine. The optimization of the fabrication technique is required to unravel the endless potential of biomaterials, shedding light on this promising interdisciplinary field, which includes both tissue engineering and drug delivery system approaches. © Springer Nature Singapore Pte Ltd 2019

Re-186 and Sm-153 dosimetry based on scintigraphic imaging data in skeletal metastasis palliative treatment and Monte Carlo simulation

Optimum treatment planning of patients suffering from painful skeletal metastases requires accurate calculations concerning absorbed dose in metastatic lesions and critical organs, such as red marrow. Delivering high doses to tumor cells while limiting radiation dose to normal tissue, is the key for successful palliation treatment. The aim of this study is to compare the dosimetric calculations, obtained by Monte Carlo (MC) simulation and the MIRDOSE model, in therapeutic schemes of skeleton metastatic lesions, with Rhenium-186 (Sn)-HEDP and Samarium-153 -EDTMP. A bolus injection of 1295 MBq (35mCi) Re-186-HEDP was infused in 11 patients with multiple skeletal metastases. The administered dose for the 8 patients who received Sm-153 was 1 mCi /kg. Planar scintigraphic images for the two groups of patients were obtained, 24 h, 48 h and 72 h post injection, by an Elscint Apex SPX gamma camera. The images were processed, utilizing ROI quantitative methods, to determine residence times and radionuclide uptakes. Dosimetric calculations were performed using the patient specific scintigraphic data by the MIRDOSE3 code of MIRD. Also, MCNPX was employed, simulating the distribution of the radioisotope in the ROI and calculating the absorbed doses in the metastatic lesion, and in critical organs. Summarizing, there is a good agreement between the results, derived from the two pathways, the patient specific and the mathematical, with a deviation of less than 9% for planar scintigraphic data compared to MC, for both radiopharmaceuticals

Quantification of myocardial perfusion in 3D SPECT images-stress/rest volume differences: 3D myocardium images quantification

Our attempt consists of modelling the heart left ventricle at stress and rest situation, using the myocardial scintigraphic data and focuses on how to demonstrate differences in obtained 3D stress/rest images. 70 cardiac patients had completed myocardium tests by Tc-99m tetrofosmin and a GE-Starcam - 4000 SPECT gamma - camera. SPECT (Single Photon Emission Computed Tomography) slices were created and used. The myocardial perfusion was estimated by comparing those slices and the suspicion of an ischemia was indicated. 3D myocardium images were reconstructed by GE Volumetrix software in the GE Xeleris processing system by FBP reconstruction method, Hanning frequency 0.8 filter and a ramp filter and transferred in a Dicom format. The Dicom file, for each patient and each phase is imported to MATLAB 7.8 (R2009a). A series of isocontour surfaces were studied, in order to identify the appropriate threshold value, which isolates the myocardium surface from the rest area of the image. Based on the previously calculated threshold value, the myocardium volume was evaluated and be reconstructed in a 3D image. The possible difference relating to the rest and stress data of the 3D images, in voxels, was calculated, using MATLAB image processing analysis; the quantification and analysis of differences was followed. We tried to determine an index of quantification and define the global quantitative defect size as a fraction of the myocardial volume area in 3D images that will give confidence in cardiac perfusion efficiency recognition by SPECT. © 2010 IEEE

Quantification of myocardial perfusion in 3D SPECT images-stress/rest volume differences: 3D myocardium images quantification

Our attempt consists of modelling the heart left ventricle at stress and rest situation, using the myocardial scintigraphic data and focuses on how to demonstrate differences in obtained 3D stress/rest images. 70 cardiac patients had completed myocardium tests by Tc-99m tetrofosmin and a GE-Starcam - 4000 SPECT gamma - camera. SPECT (Single Photon Emission Computed Tomography) slices were created and used. The myocardial perfusion was estimated by comparing those slices and the suspicion of an ischemia was indicated. 3D myocardium images were reconstructed by GE Volumetrix software in the GE Xeleris processing system by FBP reconstruction method, Hanning frequency 0.8 filter and a ramp filter and transferred in a Dicom format. The Dicom file, for each patient and each phase is imported to MATLAB 7.8 (R2009a). A series of isocontour surfaces were studied, in order to identify the appropriate threshold value, which isolates the myocardium surface from the rest area of the image. Based on the previously calculated threshold value, the myocardium volume was evaluated and be reconstructed in a 3D image. The possible difference relating to the rest and stress data of the 3D images, in voxels, was calculated, using MATLAB image processing analysis; the quantification and analysis of differences was followed. We tried to determine an index of quantification and define the global quantitative defect size as a fraction of the myocardial volume area in 3D images that will give confidence in cardiac perfusion efficiency recognition by SPECT. © 2010 IEEE

Patient-specific dosimetry in radionuclide therapy

This study presents an attempt to compare individualised palliative treatment absorbed doses, by planar images data and Monte Carlo simulation, in two in vivo treatment cases, one of bone metastases and the other of liver lesions. Medical Internal Radiation Dose schema was employed to estimate the absorbed doses. Radiopharmaceutical volume distributions and absorbed doses in the lesions as well as in critical organs were also calculated by Monte Carlo simulation. Individualised planar data calculations remain the method of choice in internal dosimetry in nuclear medicine, but with the disadvantage of attenuation and scatter corrections lack and organ overlay. The overall error is about 7 % for planar data calculations compared with that using Monte Carlo simulation. Patient-specific three-dimensional dosimetric calculations using single-photon emission computed tomography with a parallel computed tomography study is proposed as an accurate internal dosimetry with the additional use of dose-volume histograms, which express dose distributions in cases with obvious inhomogeneity. © The Author 2011. Published by Oxford University Press. All rights reserved

The impact of scattering and peak spectrum of i-123 in scintigraphy by I-123 MIBG

Metaiodobenzylguanidine (MIBG) scintigraphy is used to image tumors of neuroendocrine origin and study disorders of sympathetic innervation of the myocardium. Scintigraphic imaging methods offer the possibility of qualitative and quantitative assessment of tracer concentration. Accurate correction for the physical degrading factors (attenuation, scatter, partial volume effects) is demanded. An analytical study of the I-123 energy spectrum, scattering and attenuation contribution to the resulting image of an I-123 MIBG scintigraphy, has been undergone, so as to improve the data that could be collected by I-123-MIBG use. In this work, quantitative data were gathered at various source depths, volumes and crystal to phantom distances to determine the effect of these variables on source activity data. The final image is being extracted from the combination of three different images, each and every one being acquired by a different energy window. The middle one has been obtained from the main I-123 photopeak and the others, from the left and right peaks respectively. The problem of Compton scattering as the dominant photon interaction phenomenon and its impact on both the quality of clinical images and the accuracy of quantitative analysis is taken into consideration for a scatter modeling in non-uniform media. © 2010 World Scientific Publishing Co. Pte. Ltd

Non-canonical functions of the ARF tumor suppressor in development and tumorigenesis

P14ARF (ARF; Alternative Reading Frame) is an extensively characterized tumor suppressor which, in response to oncogenic stimuli, mediates cell cycle arrest and apoptosis via p53-dependent and independent routes. ARF has been shown to be frequently lost through CpG island promoter methylation in a wide spectrum of human malignancies, such as colorectal, prostate, breast, and gastric cancers, while point mutations and deletions in the p14ARF locus have been linked with various forms of melanomas and glioblastomas. Although ARF has been mostly studied in the context of tumorigenesis, it has been also implicated in purely developmental processes, such as spermatogenesis, and mammary gland and ocular development, while it has been additionally involved in the regulation of angiogenesis. Moreover, ARF has been found to hold important roles in stem cell self-renewal and differentiation. As is often the case with tumor suppressors, ARF functions as a pleiotropic protein regulating a number of different mechanisms at the crossroad of development and tumorigenesis. Here, we provide an overview of the non-canonical functions of ARF in cancer and developmental biology, by dissecting the crosstalk of ARF signaling with key oncogenic and developmental pathways. © 2021 by the authors. Licensee MDPI, Basel, Switzerland

A Review on Platelet Activating Factor Inhibitors: Could a New Class of Potent Metal-Based Anti-Inflammatory Drugs Induce Anticancer Properties?

In this minireview, we refer to recent results as far as the Platelet Activating Factor (PAF) inhibitors are concerned. At first, results of organic compounds (natural and synthetic ones and specific and nonspecific) as inhibitors of PAF are reported. Emphasis is given on recent results about a new class of the so-called metal-based inhibitors of PAF. A small library of 30 metal complexes has been thus created; their anti-inflammatory activity has been further evaluated owing to their inhibitory effect against PAF in washed rabbit platelets (WRPs). In addition, emphasis has also been placed on the identification of preliminary structure-activity relationships for the different classes of metal-based inhibitors. © 2017 Vasiliki D. Papakonstantinou et al

The technology of transdermal delivery nanosystems: from design and development to preclinical studies

Transdermal administration has gained much attention due to the remarkable advantages such as patient compliance, drug escape from first-pass elimination, favorable pharmacokinetic profile and prolonged release properties. However, the major limitation of these systems is the limited skin penetration of the stratum corneum, the skin's most important barrier, which protects the body from the insertion of substances from the environment. Transdermal drug delivery systems are aiming to the disruption of the stratum corneum in order for the active pharmaceutical ingredients to enter successfully the circulation. Therefore, nanoparticles are holding a great promise because they can act as effective penetration enhancers due to their small size and other physicochemical properties that will be analyzed thoroughly in this report. Apart from the investigation of the physicochemical parameters, a comparison between the different types of nanoparticles will be performed. The complexity of skin anatomy and the unclear mechanisms of penetration should be taken into consideration to reach some realistic conclusions regarding the way that the described parameters affect the skin permeability. To the best of the authors knowledge, this is among the few reports on the literature describing the technology of transdermal delivery systems and how this technology affects the biological activity. © 2021 Elsevier B.V