Development of a Topical 48-H Release Formulation as an Anti-scarring Treatment for Deep Partial-Thickness Burns

The purpose of this study was to develop pirfenidone (PF) ointment formulations for a dose finding study in the prophylactic treatment of deep partial-thickness burns in a mouse model. A preformulation study was performed to evaluate the solubility of PF in buffers and different solvents and its stability. Three different formulations containing 1, 3.5, and 6.5% w/w PF were prepared and optimized for their composition for testing in mice. Optimized formulations showed promising in vitro release profiles, in which 20-45% of PF was released in the first 7 h and 70-90% released within 48 h. The rheological properties of the ointment remained stable throughout storage at 25 ± 2°C/60% RH. Animal studies showed treatments of burn wounds during the inflammatory stage of wound healing with PF ointments at different drug concentrations had no adverse effects on reepithelization. Moreover, 6.5% PF ointment (F3) reduced the expression of pro-inflammatory cytokines IL-12p70 and TNFα. This study suggests that hydrocarbon base ointment could be a promising dosage form for topical delivery of PF in treatment of deep partial-thickness burns

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

Stem Cells Grown in Osteogenic Medium on PLGA, PLGA/HA, and Titanium Scaffolds for Surgical Application

Abstract Pluripotent adipose tissue-derived stem cells (hASCs) can differentiate into various mesodermal cell types such as osteoblasts, chondroblasts, and myoblasts. We isolated hASCs from subcutaneous adipose tissue during orthopaedic surgery and induced the osteogenic differentiation for 28 days on three different synthetic scaffolds such as polylactide-co-glycolide (PLGA), polylactide-co-glycolide/hydroxyapatite (PLGA/HA), and trabecular titanium scaffolds (Ti6Al4V). Pore size can influence certain criteria such as cell attachment, infiltration, and vascularization. The aim of this study was to investigate the performance of PLGA and PLGA/HA scaffolds with a higher porosity, ranging between 75% and 84%, with respect to Ti scaffolds but with smaller pore size, seeded with hASCs to develop a model that could be used in the treatment of bone defects and fractures. Osteogenesis was assessed by ELISA quantitation of extracellular matrix protein expression, von Kossa staining, X-ray microanalysis, and scanning electron microscopy. The higher amount of protein matrix on the Ti scaffold with respect to PLGA and PLGA/HA leads to the conclusion that not only the type of material but the structure significantly affects cell proliferation

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

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