Effects of ionizing radiation sterilization on microparticulate drug delivery systems based on poly-alfa-hydroxyacids: an overview.

Ionizing radiation treatment is particularly advantageous as a sterilization technique for polymeric drug delivery systems. In recent years several authors have investigated this topic with interesting and sometimes controversial results. This overview was aimed at gathering and critically discussing the studies performed on the effect of ionizing radiation sterilization on microparticulate drug delivery systems made of poly-α- hydroxyacids. The results reported in the literature showed that ionizing radiation always led to a decrease in poly-α-hydroxyacids molecular weight. This effect was strictly related to irradiation dose, irradiation conditions, and depended on the starting polymer molecular weight. The presence of a drug and/or an additive inside the polymeric micromatrix could affect polymer behavior upon irradiation and consequently drug release behavior. Electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR) proved to be useful techniques to elucidate the radiolytic mechanisms and the drug /polymer interaction upon irradiation

High efficiency vibrational technology (HEVT) for cell encapsulation in polymeric microcapsules

Poly(methyl-methacrylate) (PMMA) is a biocompatible and non-biodegradable polymer widely used as biomedical material. PMMA microcapsules with suitable dimension and porosity range are proposed to encapsulate live cells useful for tissue regeneration purposes. The aim of this work was to evaluate the feasibility of producing cell-loaded PMMA microcapsules through “high effciency vibrational technology” (HEVT). Preliminary studies were conducted to set up the process parameters for PMMA microcapsules production and human dermal fibroblast, used as cell model, were encapsulated in shell/core microcapsules. Microcapsules morphometric analysis through optical microscope and scanning electron microscopy highlighted that uniform microcapsules of 1.2 mm with circular surface pores were obtained by HEVT. Best process conditions used were as follows: frequency of 200 Hz, voltage of 750 V, flow rate of core solution of 10 mL/min, and flow rate of shell solution of 0.5 bar. Microcapsule membrane allowed permeation of molecules with low and medium molecular weight up to 5900 Da and prevented diffusion of high molecular weight molecules (11,000 Da). The yield of the process was about 50% and cell encapsulation efficiency was 27% on total amount. The cell survived and growth up to 72 h incubation in simulated physiologic medium was observed

The microfluidic technique and the manufacturing of polysaccharide nanoparticles

Themicrofluidic technique has emerged as a promising tool to accelerate the clinical translation of nanoparticles, and its application affects several aspects, such as the production of nanoparticles and the in vitro characterization in the microenvironment, mimicking in vivo conditions. This review covers the general aspects of the microfluidic technique and its application in several fields, such as the synthesis, recovering, and samples analysis of nanoparticles, and in vitro characterization and their in vivo application. Among these, advantages in the production of polymeric nanoparticles in a well-controlled, reproducible, and high-throughput manner have been highlighted, and detailed descriptions of microfluidic devices broadly used for the synthesis of polysaccharide nanoparticles have been provided. These nanoparticulate systems have drawn attention as drug delivery vehicles over many years; nevertheless, their synthesis using themicrofluidic technique is still largely unexplored. This review deals with the use of the microfluidic technique for the synthesis of polysaccharide nanoparticles; evaluating features of the most studied polysaccharide drug carriers, such as chitosan, hyaluronic acid, and alginate polymers. The critical assessment of the most recent research published in literature allows us to assume that microfluidics will play an important role in the discovery and clinical translation of nanoplatforms

Electrospun tubular vascular grafts to replace damaged peripheral arteries: A preliminary formulation study

Polymeric tubular vascular grafts represent a likely alternative to autologous vascular grafts for treating peripheral artery occlusive disease. This preliminary research study applied cutting-edge electrospinning technique for manufacturing prototypes with diameter ≤ 6 mm and based on biocompatible and biodegradable polymers such as polylactide-polycaprolactone, polylactide-co-glycolide and polyhydroxyethylmethacrylate combined in different design approaches (layering and blending). Samples were characterized about fiber morphology, diameter, size distribution, porosity, fluid uptake capability, and mechanical properties. Biocompatibility and cell interaction were evaluated by in vitro test. Goal of this preliminary study was to discriminate among the prototypes and select which composition and design approach could better suit tissue regeneration purposes. Results showed that electrospinning technique is suitable to obtain grafts with a diameter < 6 mm and thickness between 140 ± 7–175 ± 4 μm. Scanning electron microscopy analysis showed fibers with suitable micrometric diameters and pore size between 5 and 35 μm. polyhydroxyethylmethacrylate provided high hydrophilicity (≃ 100◦) and optimal cell short term proliferation (cell viability ≃ 160%) in accordance with maximum fluid uptake ability (300–350%). Moreover, addition of polyhydroxyethylmethacrylate lowered suture retention strength at value < 1 N. Prototypes obtaining combining polylactide-co-glycolide and polylactide-coglycolide/ polyhydroxyethylmethacrylate with polylactide-polycaprolactone in a bilayered structure showed optimal mechanical behavior resembling native bovine vessel

Boron-loaded liposomes in the treatment of hepatic metastases: preliminary investigation by autoradiography analysis.

Boronophenylalanine (BPA)-loaded conventional and stabilized liposomes were prepared by the reversed phase evaporation method to treat liver metastases by boron neutron capture therapy. Conventional vesicles were composed of phosphatidylcholine and cholesterol, molar ratio 1:1. To obtain stealth liposomes, GM1 or PEG were included in the lipidic bilayer at a concentration of 6.67 or 5 mol%, respectively. Large unilamellar vesicles were formulated encapsulating BPA in the liposome aqueous compartment as a complex with fructose; BPA free base also was embedded into the lipidic bilayer. In vivo experiments were carried out after intravenous injection of liposome suspensions in BD-IX strain rats in which liver metastases had been induced. Alpha particle spectroscopy associated with histological analysis was performed to visualize boron spatial distribution in liver. Simultaneously, tissue boron concentrations were determined using inductively coupled plasma-mass spectroscopy. Results showed that PEG-modified liposomes accumulated boron in therapeutic concentrations (30 micrograms boron/g tissue) in metastatic tissue. The PEG-liposomes could be further explored in enhancing boron delivery to tumor cells

Diaminobenzidine photoconversion is a suitable tool for tracking the intracellular location of fluorescently labelled nanoparticles at transmission electron microscopy.

Chitosan-based nanoparticles (NPs) deserve particular attention as suitable drug carriers in the field of pharmaceutics, since they are able to protect the encapsulated drugs and/or improve their efficacy by making them able to cross biological barriers (such as the blood-brain barrier) and reach their intracellular target sites. Understanding the intracellular location of NPs is crucial for designing drug delivery strategies. In this study, fluorescently-labelled chitosan NPs were administered in vitro to a neuronal cell line, and diaminobenzidine (DAB) photoconversion was applied to correlate fluorescence and transmission electron microscopy to precisely describe the NPs intracellular fate. This technique allowed to demonstrate that chitosan NPs easily enter neuronal cells, predominantly by endocytosis; they were found both inside membrane-bounded vesicles and free in the cytosol, and were observed to accumulate around the cell nucleus

The effect of Process Parameters on Alignment of Tubular Electrospun Nanofibers for Tisue Regeneration Purposes

Electrospinning is known to be an effective and straightforward technique to fabricate polymer non woven matrices made of nano and microfibers. Micro patterned morphology of electrospun matrices results to be outmost advantageous in the biomedical field, since it is able to mimic extracellular matrix (ECM), and favors cell adhesion and proliferation. Controlling electrospun fibers alignment is crucial for the regenerative purposes of certain tissues, such as neuronal and vascular. In this study we investigated the impact of electrospinning process parameters on fiber alignment in tubular nanofibrous matrices made of Poly (L-lactide-co-ε-caprolactone) (PLA-PCL); a Design of Experiments (DoE) approach is here proposed in order to statistically set up the process parameters. The DoE was studied keeping constants the previously set material and environmental parameters; voltage, flow rate and mandrel rotating speed were the process parameters here investigated as variables. Orientation analysis was based on ImageJ and plugin Orientation J analysis of SEM images. The results show that voltage combined with flow rate has significant impact on electrospun fiber orientation, and the greatest orientation is achieved when all the three input parameters (voltage, flow rate and mandrel rotation speed) are at their maximum value

Assessment of different manufacturing techniques for the production of bioartificial scaffolds as soft organ transplant substitutes

Introduction: The problem of organs’ shortage for transplantation is widely known: different manufacturing techniques such as Solvent casting, Electrospinning and 3D Printing were considered to produce bioartificial scaffolds for tissue engineering purposes and possible transplantation substitutes. The advantages of manufacturing techniques’ combination to develop hybrid scaffolds with increased performing properties was also evaluated.Methods: Scaffolds were produced using poly-L-lactide-co-caprolactone (PLA-PCL) copolymer and characterized for their morphological, biological, and mechanical features.Results: Hybrid scaffolds showed the best properties in terms of viability (&gt;100%) and cell adhesion. Furthermore, their mechanical properties were found to be comparable with the reference values for soft tissues (range 1–10 MPa).Discussion: The created hybrid scaffolds pave the way for the future development of more complex systems capable of supporting, from a morphological, mechanical, and biological standpoint, the physiological needs of the tissues/organs to be transplanted

Different Molecular Weight Chitosan Microspheres: Influence on Drug Loading and Drug Release

Influence of chitosan molecular weight on drug loading and drug release of drug-loaded chitosan microspheres was studied. Chitosans of 70,000 (LC), 750,000 (MC), and 2,000,000 (HC) molecular weight were employed alone or as mixtures (HC/LC 1:1-1:2 w/w). Ketoprofen (ket) was chosen as the model drug to be encapsulated. Microspheres characterized by different theoretical polymer/drug ratios were prepared (2:1, 1:1, 1:2 w/w). Satisfactory ket contents were obtained for all batches of chitosan microspheres with the theoretical polymer/drug ratio 1:2 w/w; microspheres made of HC/LC (1:2 w/w) were characterized by good drug content and encapsulation efficiency independent by polymer/drug ratio. Prepared chitosan microparticulate delivery systems can modulate ket release within 48 hr. Microspheres consisting of HC/LC (1:2 w/w) were the most suitable formulation in controlling drug release